Monomeric and dimeric complexes of pyrimidine-4,6-dicarboxylic acid with organometallic fac-[M(CO)3]+ (M = Re and 99mTc) core as radiopharmaceutical probes

Monomeric and dimeric complexes of pyrimidine-4,6-dicarboxylic acid with organometallic fac-[M(CO)3]+ (M = Re and 99mTc) core as radiopharmaceutical probes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Monomeric and dimeric complexes of pyrimidine-4,6-dicarboxylic acid with organometallic fac-[M(CO) 3 ] + (M = Re and 99m Tc) core as radiopharmaceutical probes Janvier Mukiza, Gratien Habarurema, Jurdas Sezirahiga, Theonille Mukabagorora, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4381286/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The current study describes the synthesis of monomeric and dimeric complexes of pyrimidine-4,6-dicarboxylic acid (H 2 pmdc) ligand with the organometallic fac -[M(CO) 3 ] + (M = Re and 99m Tc) core which are the model for future design of imaging, therapeutic and theranostic radiopharmaceuticals. Monomeric complexes [M(CO) 3 (OH 2 )(Hpmdc)] (M = Re ( 1 ) and 99m Tc ( 2 )) were formed from the reaction of H 2 pmdc with [Re(CO) 5 Br] and [ 99m Tc(CO) 3 (OH 2 ) 3 ] + in aqueous solution respectively. The reaction of [Re(CO) 5 Br] with H 2 pmdc in ethanol (EtOH) led to the monomeric complex [Re(CO) 3 (OH 2 )(etpmdc)] ( 3 ), where etpmdc − is 6-(ethoxycarbonyl)pyrimidine-4-carboxylate anion which was formed from the mono-esterification of H 2 pmdc in parallel with its coordination to the fac -[Re(CO) 3 ] + unit. Dimeric complex (Et 3 NH) 2 [(µ-pmdc) 2 (Re(CO) 3 ) 2 ( 4 ) was obtained from the reaction of [Re(CO) 5 Br] with H 2 pmdc in water with addition of triethylamine (Et 3 N) as supporting base. The chemical identification of 1 , 3 an d 4 was achieved by using 1 HNMR, 13 CNMR, IR, ESI-MS and elemental analysis. Complex 3 was furtherly identified by using single crystal X-ray crystallography. The structural similarities of 1 and 2 was assessed by coinjection in the HPLC with UV/Vis detection coupled with a γ-detector followed by comparison of retention times of the γ-peak of 2 and the UV-peak of 1 which allowed unambiguous identification of 2 . Heterodinuclear 99m Tc/Re complex [(µ-pmdc) 2 (Re(CO) 3 )( 99m Tc(CO) 3 ) 2 )] 2− ( 5 ) was formed by reacting H 2 pmdc with [ 99m Tc(CO) 3 (OH 2 ) 3 ] + and [Re(CO) 5 Br] in aqueous solution. In parallel, the reaction also yielded complexes 1 and 2 . The formation of 5 was assessed by injection in the HPLC with UV/Vis detection coupled with a γ-detector which displayed the radiochemical peak with the corresponding UV peak equivalent to that of the homologous non-radioactive complex 4 . Monomeric complex Dimeric complex Pyrimidine-4 6-dicarboxylic acid Rhenium Technetium Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction Pyrimidine-4,6-dicarboxylic acid (H 2 pmdc) is naturally occurring heterocyclic compound, and it is found in many organisms as building block of biological molecules, and involved in different metabolic pathways [ 1 , 2 ]. It is involved in the synthesis of purines and pyrimidines bases, which are the building blocks of DNA and RNA, and regulation of the Krebs cycle during glucose metabolism [ 1 , 3 ]. In addition, H 2 pmdc is of interest as it is potentially applied in the synthesis of a variety of compounds, including antibiotics, antivirals, and other drugs [ 1 , 2 ]. Due to its large number of donor atoms and flexibility as small molecule, H 2 pmdc ligand has shown a remarkable capacity in the development of coordination chemistry [ 4 ]. The diversity of its coordination mode to metal ions is reflected in the variety of known and stable metal complexes with this ligand, which vary from monomers to ligand-bridged dimers and multimers [ 4 – 8 ]. Furthermore, the H 2 pmdc contains two carboxylic acid groups and two imine nitrogens which is advantage in the coordination chemistry since it can be easily functionalized and derivatized [ 5 – 8 ]. Rhenium (Re) and technetium (Tc) are located in Group VII on the Periodic Table of elements and have comparable atomic radii, and consequently display similar coordination chemistry [ 11 ]. Therefore, the chemistry of rhenium is used for modelling one of technetium [ 9 , 10 ]. Due to their location in the middle of the d-block of transition metals, Re and Tc exhibit the properties of both early and later transition metals [ 9 , 11 , 12 ], and display the oxidation state which varies from − 1 to + 7 [ 12 ]. The chemistry of Re and Tc is continuing to attract the researchers due to the potential application of these elements in nuclear medicine [ 13 , 11 ]. Rhenium radioisotopes 186/188 Re are γ and β-emitters and applied in therapeutic nuclear medicine, while technetium radioisotope 99m Tc is γ-emitter and applied in nuclear medicine imaging procedures [ 11 – 15 ]. The similarity in the coordination chemistry of Re and Tc makes possible to share the same biodistribution partners in the body for analogous radiopharmaceuticals based on these elements, and enable the monitoring of their biodistribution using the same γ-ray camera [ 16 ]. Organometallic fac -[M(CO) 3 ] + (M = Re and Tc) core dominates the chemistry of rhenium(I) and technetium(I), and it is well known by its small size, three vacant coordination sites and three flexible and facially arranged CO ligands [ 11 , 17 – 19 ]. The fac -[M(CO) 3 ] + (M = Re and Tc) core displays d 6 and low-spin electronic configuration, and its complexes are characterized by a distorted octahedral geometry and high kinetic and thermodynamic stability [ 18 – 20 ]. It is routinely coordinate to different chelating ligands leading to the complexes which structurally vary from monomers to ligand-bridged multimers, and even from metal-metal multiply bonded multimers to clusters [ 11 , 17 – 19 ]. Organometallic complexes based on the fac -[M(CO) 3 ] + (M = Re and Tc) core have attracted much attention due particularly to their possible application in the development of radiopharmaceuticals which involve imaging 99m Tc and therapeutic 186/188 Re compounds [ 15 , 21 – 23 ]. Due to the small size of octahedral complexes based on the the fac -[M(CO) 3 ] + (M = Re and Tc) core considerably to the octahedral or square-pyramidal complexes of the corresponding metals in higher oxidation states, they are considered less likely to impact important characteristics of bio-molecules to which they are conjugated to [ 14 , 24 ]. Pyrimidine derivatives with electron-rich sp 2 -hybridized nitrogen atoms have been identified as convenient ligands to stabilize the fac -[M(CO) 3 ] + (M = Re and Tc) core [ 25 , 26 ]. Despite their variety of possible applications, rhenium and technetium complexes based on the fac -[M(CO) 3 ] + core (M = Re and Tc) with pyrimidine derivative ligands have not been extensively explored [ 21 , 22 ], and few examples have been reported. The fac -[M(CO) 3 ] + core (M = Re and Tc) complexes with pyrimidine nucleoside derivatives have been reported and provided a convenient platform for drugs development [ 27 ]. Recently, complexes of the fac -[M(CO) 3 ] + (M = Re and 99 Tc/ 99m Tc) core with pyrimidine based ligands typically orotic acid and its derivatives have been reported [ 19 ]. The current study highlights on the fac -[M(CO) 3 ] + (M = Re and 99m Tc) core complexes with pyrimidine-4,6-dicarboxylic acid (H 2 pmdc) (Fig. 1 ) which are the model for future design of imaging, therapeutic and theranostic radiopharmaceuticals. The reported rhenium complexes were characterized by using 1 HNMR, 13 CNMR, IR and ESI-MS, and complex 3 was additionally characterized by using single crystal X-ray crystallography. Identity of the reported monomeric rhenium and technetium complexes was confirmed by coinjection in the same HPLC with UV/Vis detection coupled with a γ-detector followed by comparison of retention times for UV- and γ-signals. Evidence of the formation of heterodinuclear 99m Tc/Re complex 5 was assessed by the comparison of its HPLC profile with the HPLC profile of its homologous rhenium dimer complex 4 fully characterized by routine chemistry analytical techniques. 2. Experimental 2.1. Materials and instrumentation Caution 99m Tc is weak γ-emitters. All experiments involving 99m Tc were done in the laboratories approved for working with the low-level radioactive materials. All reactions and solution preparations were carried out under an inert N 2 atmosphere. [ 99m TcO4] − was eluted from a 99 Mo / 99m Tc Ultratechnekow FM generator from Mallinckrodt Schweiz AG. The [Re(CO) 5 Br] and pyrimidine-4,6-dicarboxylic acid (H 2 pmdc) were obtained from the Sigma Aldrich. The 99m Tc precursor complex [ 99m Tc(CO) 3 (OH 2 ) 3 ] + was obtained from the reduction of [ 99m TcO 4 ] − according to the reported literature method [ 28 ]. The purity of the reported rhenium complexes was confirmed by Ultraperformance Liquid Chromatographic (UPLC) with a Nucleosil C-18 column (100 Å, 5 µm, 250 × 4 mm) which was eluted with a flow rate of 0.5 ml min − 1 , using 0.1% trifluoro-acetic acid (TFA) in H 2 O (solvent A) and acetonitrile (solvent B). 1 HNMR and 13 CNMR spectra were recorded on Bruker Advance 400 and 500 MHz NMR spectrometer. Deuterated methanol (CD 3 OD) and water (D 2 O) were used as NMR solvents and the peak positions were obtained relatively to tetramethylsilane (SiMe 4 ). The infrared spectra were recorded on a Perkin-Elmer FT-IR Spectrum Two spectrometer, using ATR technique, and applied as neat samples. HPLC analyses were performed on a Merck Hitachi LaChrom L 7100 pump coupled to a Merck Hitachi LaChrom L7455 photo diode array. UV/Vis detection was performed at 250 nm. The detection of radioactive 99m Tc complexes was performed with Berthold Technologies Flowstar LB513 radiodetectors equipped with YG/BGO cells, respectively. The radiodetectors were coupled to the HPLC systems. Separations were achieved on a Macherey-Nagel C18 reversed-phase column (EC-250 / 3 Nucleosil 100-5 C18) using gradients of CF 3 COOH (0.1% in H 2 O, solvent A) and MeOH (solvent B). Comparison of the HPLC retention times for the 99m Tc compounds with the corresponding Re compounds confirms the complexes’ identity. Liquid chromatography (ESI-MS) was analysed using BrukerEsquire HCT (ESI) instrument. The elemental analyses for carbon, hydrogen and nitrogen were performed on a Vario EL (ElementarAnalysensystem GmbH) instrument. Single-crystal X-ray diffraction data was collected at 160(1) K on a Rigaku OD XtaLAB Synergy, Dualflex, Pilatus 200K diffractometer using a single wavelength X-ray source (Mo Kα radiation: λ = 0.71073 Å) [ 29 ] from a micro-focus sealed X-ray tube and an Oxford liquid-nitrogen Cryostream cooler. The selected suitable single crystal was mounted using polybutene oil on a flexible loop fixed on a goniometer head and immediately transferred to the diffractometer. Pre-experiment, data collection, data reduction and analytical absorption correction [ 30 ] were performed with the program suite CrysAlisPro 20 [ 31 ]. Using Olex2 , [ 32 ] the structure was solved with the SHELXT [ 33 ] small molecule structure solution program and refined with the SHELXL 2018/3 program package [ 34 ] by full-matrix least-squares minimization on F [ 30 ]. PLATON [ 34 , 35 ] was used to check the result of the X-ray analysis. For more details about the data collection and refinement parameters, see the CIF file. 2.2. Synthesis of [Re(CO) 3 (OH 2 )(Hpmdc)] (1) [Re(CO) 5 Br] (34.92 mg, 0.086 mmol) and pyrimidine-4,6-dicarboxylic acid (H 2 pmdc) (14.45 mg, 0.086 mmol) were added to 10 cm 3 of distilled water. The resulting colorless mixture was heated under refluxed for 6 hours, giving an orange-yellow solution, which was filtered after being cooled to room temperature. No precipitate was obtained. The solvent was removed by evaporation and the yellow-orange precipitate of 1 was purified by washing it several times by dichloromethane and diethylether and dried under vacuum. Yield ( 1 ) = 65% (25.45 mg). Anal. Calcd. for C 9 H 5 N 2 O 8 Re (Mol. Wt. = 455.35 g/mol): C, 23.74; H, 1.11; N, 6.15. Found: C, 23.77; H, 1.10; N, 6.13. IR (νmax/cm − 1 ): ѵ(O − H) 3225, 3110; ѵ(C ≡ O)) 2042, 1908, 1932; ѵ(C = O)) 1712; ѵ(C = N) 1636, 1599. 1 HNMR (295K, D 2 O, 400MHz) δ ppm: 8.56 (s, 1H, H(3)), 9.66 (s, 1H, H(6)). 13 CNMR (295K, CD 3 OD, 125MHz) δ ppm: 122.76 (C(3)), 159.52 (C(6)), 162.97 (C(4)), 167.41 (C(2)), 171.40 (C(b)), 175.89 (C(a)), 194.96, 198.01 (CO). ESI-MS (m/z): [C 9 H 6 N 2 O 8 Re] + or [ 1 + H] + , calculated: 456.97, found: 457.03; [C 9 H 4 N 2 O 7 Re] + or [ 1 -H 2 O + H] + , calculated: 438.96, found: 439.06, [C 11 H 7 N 3 O 7 Re] + or [ 1 + MeCN + H-H 2 O] + , calculated: 479.98, found: 479.99. UPLC (retention time min.): 1.80. 2.3. Synthesis of [ 99m Tc(CO) 3 (OH 2 )(Hpmdc)] (2) 300 µl of [ 99m Tc(CO) 3 (OH 2 ) 3 ] + in water were mixed with 300µl of 0.01M aqueous solution of pyrimidine-4,6-dicarboxylic acid (H 2 pmdc) in vial which was sealed and flushed with N 2 for 15 min. The mixture was heated at 80 o C for 30 min. The solution was brought to r.t. Injection of the solution in the HPLC equipped by gamma and UV detectors displayed the product with a radiochemical yield > 99%. Heating under microwave at the same temperature gave the product in approximately the same yields. The nature of complex 2 was identified by coinjection with [Re(CO) 3 (OH 2 )(Hpmdc)] ( 1 ) in the same HPLC equipped with UV/Vis detection coupled with γ-detector followed by comparison of retention time. 2.4. Synthesis of [Re(CO) 3 (OH 2 )(etpmdc)] (3) [Re(CO) 5 Br] (34.92 mg, 0.086 mmol) and pyrimidine-4,6-dicarboxylic acid (H 2 pmdc) (14.45 mg, 0.086 mmol) were added to 10 cm 3 of ethanol. The resulting colorless mixture was heated under refluxed for 6 hours, giving orange solution, which was filtered after being cooled to room temperature, giving an orange precipitate of [Re(CO) 3 (OH 2 )(etpmdc)] ( 3 ). Compound 3 was purified by washing it several times by ethanol and diethylether, and dried under vacuum. Orange-yellow crystals suitable for X-ray diffraction analysis were obtained by the slow evaporation of the filtrate over 4 weeks at room temperature. The crystals of 3 have been also grown from recrystallization of precipitate of 3 in ethanol with 20% of dichloromethane in 3 weeks by the slow evaporation of solvents at room temperature. Yield (1) = 87% (31.18 mg). Anal. Calcd. for C 11 H 9 N 2 O 8 Re (Mol. Wt. = 483.41 g/mol): C, 27.33; H, 1.88; N, 5.80. Found: C, 27.29; H, 1.85; N, 5.77. IR (νmax/cm − 1 ): ѵ(O − H) 3364; ѵ(C ≡ O)) 1873, 1883, 2015; ѵ(C = O)) 1689; ѵ(C = N) 1585, 1581; ѵ(C − H) 3089, 3091. 1 HNMR (295K, CD 3 OD, 400MHz) δ ppm: 1.45 (t, 3H, CH 3 ), 4.52 (q, 2H, CH 2 ), 4.07 (s, 2H, H 2 O), 8.61 (s, 1H, H(3)), 9.64 (s, 1H, H(6)). 13 CNMR (295K, CD 3 OD, 125MHz) δ ppm: 14.85 (CH 3 ), 64.88 (CH 2 ), 123.13 (C(3)), 160.72 (C(6)), 160.76 (C(4)), 162.34 (C(2)), 164.30 (C(b)), 173.79 (C(a)), 197.37, 197.05, 193.94 (CO). ESI-MS (m/z): [C 11 H 8 N 2 O 7 Re] + or [ 3 -H 2 O + H] + , calculated: 466.99, found: 467.21, [C 13 H 11 N 3 O 7 Re] + or [ 3 + MeCN + H-H 2 O] + , calculated: 508.02, found: 508.15. 2.5. Synthesis of (Et 3 NH) 2 [(µ-pmdc) 2 (Re(CO) 3 ) 2 ] (4) Pyrimidine-4,6-dicarboxylic acid (H 2 pmdc) (20.67 mg, 0.123 mmol) was added to [Re(CO) 5 Br] (49.95 mg, 0.123 mmol) in 10 cm 3 of distilled water and 3 drops of triethylamine (Et 3 N). The resulting colourless mixture was refluxed for 24 hours, giving an orange solution, which was filtered after being cooled to room temperature. No precipitate was formed; the filtrate was removed giving an orange precipitate of 4 which was purified by washing it several times by dichloromethane and diethylether. Yield = 85% (56.30 mg). Anal. Calcd. for C 30 H 36 N 6 O 14 Re 2 (Mol. Wt. = 1077.06 g/mol): C, 33.45; H, 3.37; N, 7.80. Found: C, 33.41; H, 3.32; N, 7.78. IR (νmax/cm − 1 ): ѵ(C ≡ O)), 2016, 1875; ѵ(C = O) 1646, ѵ(C = N) 1599, 1538, ѵ(C-H) 2988. 1 H-NMR (295K, D 2 O, ppm, 400MHz) δ ppm: 1.28 (t, 18H, 9CH 3 ), 3.20 (q, 12H, 6CH 2 ), 8.44 (s, 2H, H(3)), 9.59 (s, 2H, H(6)). 13 CNMR (295K, D 2 O, 125MHz) δ ppm: 8.04 (CH 3 ), 46.64 (CH 2 ), 120.33 (C(3)), 156.80 (C(6)), 160.48 (C(4)), 164.89 (C(2)), 168.80 (C(b)), 173.41 (C(a)), 193.00, 195.59 (CO). ESI-MS (m/z): [C 18 H 5 N 4 O 14 Re 2 ] − or [ 4 + H] − , calculated: 872.89, found: 872.91; [C 20 H 10 N 5 O 14 Re 2 ] + or [ 4 + 3H + MeCN] + , calculated: 915.93, found: 916.10. UPLC (retention time min.): 2.06. 2.6. Synthesis of [(µ-pmdc) 2 (Re(CO) 3 )( 99m Tc(CO) 3 )] 2− (5) 600 µl of [ 99m Tc(CO) 3 (OH 2 ) 3 ] + in water, 300µl of 0.1M aqueous solution of pyrimidine-4,6-dicarboxylic acid (H 2 pmdc) and [Re(CO) 5 Br] (0.84 mg, 2µmol) were mixed in vial which was sealed and flushed with N 2 for 15 min. The mixture was heated at 80 o C for 45-min. The solution was brought to r.t. and injection of the product in the HPLC equipped by gamma and UV detectors displayed complex 5 with a radiochemical yield of 35% and it is parallelly formed with complex 1 and 2 . By repeating this reaction with exclusion of [ 99m Tc(CO) 3 (OH 2 ) 3 ] + , dimeric complex 4 was also formed. 3. Results and discussion 3.1. Synthesis of [Re(CO) 3 (OH 2 )(Hpmdc)] (1), [ 99m Tc(CO) 3 (OH 2 )(Hpmdc)] (2) and [Re(CO) 3 (OH 2 )(etpmdc)] (3) Monomeric complex [Re(CO) 3 (OH 2 )(Hpmdc)] ( 1 ) was formed by reacting the chelating ligand pyrimidine-4,6-dicarboxylic acid (H 2 pmdc) with [Re(CO) 5 Br] in distilled water (Scheme 1 ). The formation of 1 was enhanced by the denticity of H 2 pmdc ligand and its good solubility in polar solvents like water. Complexes 1 is orange-yellow colored and it is soluble in polar solvents like water, ethanol and methanol and display low solubility in non-polar solvents. Technetium (99m) complex homologous of 1 typically [ 99m Tc(CO) 3 (OH 2 )(Hpmdc)] (2) was directly formed from the reaction of fac -[ 99m Tc(CO) 3 (OH 2 ) 3 ] + with H 2 pmdc in water at 80 o C for 30 min (Scheme 1 ). Complex 2 was also formed by heating aqueous fac -[ 99m Tc(CO) 3 (OH 2 ) 3 ] + solution with H 2 pmdc in microwave under the same reaction conditions. The Hpmdc − anion in the complexes 1 and 2 , coordinated to the fac -[M(CO) 3 ] + core as bidentate N,O-donor chelate, coordinating to the metal center via one of the pyrimidinic nitrogens and carboxylate-oxygen atoms, giving five-membered metallacycle ring (Scheme 1 ). The complex [Re(CO) 3 (OH 2 )(etpmdc)] ( 3 ) was obtained from the reaction of H 2 pmdc with [Re(CO) 5 Br] in ethanol. The formation of 6-(ethoxycarbonyl)pyrimidine-4-carboxylate (etpmdc − ) anion was surprisingly enhanced by [Re(CO) 5 Br]-catalysed mono-esterification of H 2 pmdc and simultaneously coordinated to the fac -[M(CO) 3 ] + core as Hpmdc − in 1 and 2 . The ability of rhenium(I) complexes [Re(CO) 5 X] (X = Cl, Br) to catalyse esterification reaction of carboxylic acid by alcohol was previously reported in the literature [ 11 ], and it is supported by the Lewis acidity character of these complexes [ 11 ]. The reaction of 5-(5-aminopyrimidine-2,4(1H,3H)-dioxamido)-1,2,3,6-tetrahedro-2,6-dioxopyrimidine-4-carboxylic acid (H 2 amp) with [Re(CO) 5 Cl] in ethanol which led to the rhenium(I) complex [Re(CO) 3 (H 2 O)(amef)] where amef is 5-(5-ammoniumpyrimidine-2,4(1H,3H)-dioxamido)-1,2,3,6-tetrahedro-2,6-dioxopyrimidine-4-ethylformate, and was formed by [Re(CO) 5 Cl]-catalysed esterification of H 2 amp by ethanol, and coordinated to the fac-[Re(CO) 3 ] + core as a bidentate N,N-donor chelate [ 11 ]. Complexes 3 is orange and it is soluble in polar solvents like water, ethanol and methanol but not soluble in non-polar solvents. Attempt to synthesize 99m Tc complex homologous of 3 in the same synthetic route as one used for the synthesis of [ 99m Tc(CO) 3 (OH 2 )(Hpmdc)] (2) with addition of ethanol was not successful but the reaction also led to complex 2 . A variety of metal complexes of pyrimidine-4,6-dicarboxylic acid (H 2 pmdc) such as lanthanide(III) [ 6 ], scandium (III) [ 7 ] and manganese(II) [ 8 ] have been reported, and H 2 pmdc ligand coordinated to the above-mentioned metal ions as in complexes 1 and 2 . To the best of our knowledge, the complexes [Re(CO) 3 (OH 2 )(Hpmdc)] ( 1 ) and [ 99m Tc(CO) 3 (OH 2 )(Hpmdc)] (2) are the first reported rhenium and technetium complexes with pyrimidine-4,6-dicarboxylic acid (H 2 pmdc) ligand. Due to the lability of aqua-ligand, complexes 1 , 2 and 3 are biologically important as aqua-ligand have been identified to exchange with a variety of biological molecules in biological system [ 19 ]. Such exchange shall not affect the rest part of complexes 1 , 2 and 3 as result of high kinetic and thermodynamic stability of complexes based on the organometallic fac -[M(CO) 3 ] + (M = Re and Tc) unit, granting the potential application of these complexes as radiopharmaceutical probes. By eluting complex 1 in the ultraperformance liquid chromatography (UPLC) system, it was detected at the retention time of 1.80 min (Fig. S1 ). The vibrational peaks at 2042, 1908 and 1932 cm − 1 in the infrared spectrum of 1 (Fig. S2) are ascribed to the fac -[Re(CO) 3 ] + , and they are at 1873, 1883, 2015 cm − 1 in 3 (Fig. S6). The peaks at 3225 and 3110 cm − 1 in 1 are ascribed to the ѵ(O − H) for the free OH in the coordinated ligand and water respectively whereas the ѵ(O − H) for the OH of the coordinated water in 3 occur at 3364 cm − 1 (Figure S6). The 1 HNMR spectrum of 1 in D 2 O (Fig. S3) displayed two protons H(3) and H(6) at 8.56 and 9.66 ppm respectively. Homologous protons in 3 occur at 8.61 and 9.64 ppm respectively in the 1 HNMR of 3 measured in CD 3 OD (Fig. S7). The triplet and quartet signals at 1.45 ppm and at 4.52 ppm in the 1 HNMR of 3 are assigned to the -CH 3 and -CH 2 respectively, while the protons of the coordinated water are displayed as singlet signal at 4.07 ppm. The 13 CNMR in CD 3 OD gave the promised signals at 122.76, 159.52, 162.97, 167.41, 171.40, 175.89 ppm for 1 (Fig. S4); and 123.13, 160.72, 160.76, 162.34, 164.30, 173.79 for 3 (Fig. S8). The signals at 194.96 and 198.01 ppm are due to CO ligands in 1 and they are at 197.37, 197.05, 193.94 ppm in 3 . The signals at 14.85 and 64.88 ppm in the 13 C NMR of 3 are ascribed to -CH 3 and -CH 2 respectively. Liquid chromatography-mass spectrometry (ESI-MS) analysis of complex 1 (Fig. S5) displayed m/z peaks at 457.03 ascribed to [C 9 H 6 N 2 O 8 Re] + or [ 1 + H] + and 438.06 in accordance with [C 9 H 4 N 2 O 7 Re] + or [ 1 -H 2 O + H] + as well as 479.99 reflecting [C 11 H 7 N 3 O 7 Re] + or [ 1 + MeCN + H-H 2 O] + . Similarly, ESI-MS spectrum of 3 (Fig. S9) showed m/z peaks typically 467.21 for [C 11 H 8 N 2 O 7 Re] + or [ 3 -H 2 O + H] + , and 508.15 for [C 13 H 11 N 3 O 7 Re] + or [ 3 + MeCN + H-H 2 O] + . The Fig. 2 shows ORTEP drawing of complex 3 and its crystal details and structure refinement data are described in Table 1 . The CCDC 2260652 contains the supplementary crystallographic data for 3 , and can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif . As generally observed to rhenium(I) complexes based on the fac -[Re(CO) 3 ] + unit, the geometry around the rhenium metal center is a distorted octahedral [ 11 , 18 , 19 ], with oxygen atom of the coordinated water O(4) and two donor atoms N(1) and O(5) of etpmdc − anion in a facial arrangement as imposed by the fac -[Re(CO) 3 ] + core. Table 1 Structure refinement parameters data and selected bond lengths (Å) and angles (˚) for [Re(CO) 3 (OH 2 )(etpmdc)] ( 3 ) Structure refinement Parameters Structure refinement Parameters data Selected bond lengths (Å) and angles (˚) Chemical formula Formula weight Temperature (K) Crystal system Space group Unit cell dimensions (Å˚) Crystal size/mm 3 Volume (Å 3 ) Z Density (calc.) (g/cm 3 ) Absorption coefficient (mm − 1 ) F (000) Radiation θ range for data collection (deg) Index ranges h,k,l max Reflections collected Independent reflections Data/restraints/parameters Goodness-of-fit on F 2 Final R indexes [I > = 2σ (I)] Final R indexes [all data] Largest diff. peak and hole(e/Å 3 ) C 11 H 9 N 2 O 8 Re 483.40 160 K Monoclinic P 2 1 /c a = 7.05850(12) α = 90 b = 7.82584(13) β = 93.1000(16) c = 24.5852(5) γ = 90 0.14 × 0.08 × 0.01 1356.07(4) 4 2.368 9.006 912.0 MoKα (λ = 0.71073) 5.464 to 61.016 -10 ≤ h ≤ 10,-10 ≤ k ≤ 11,-35 ≤ l ≤ 35 41731 4123 [R int =0.0320, R sigma = 0.0157] 4123/0/208 1.148 R 1 = 0.0200, wR 2 = 0.0395 R 1 = 0.0227, wR 2 = 0.0402 1.53/-1.41 Re(1)-C(1) 1.922(3) Re(1)-C(2) 1.900(3) Re(1)-C(3) 1.900(3) Re(1)-O(4) 2.211(2) Re(1)-O(5) 2.1489(19) Re(1)-N(1) 2.179(2) C(4)-O(5) 1.272(3) C(4)-O(6) 1.235(3) C(9)-O(7) 1.213(3) C(9)-O(8) 1.309(3) C(10)-O(8) 1.474(3) C(5)-N(1) 1.349(3) C(8)-N(1) 1.348(3) C(8)-N(2) 1.327(3) C(7)-N(2) 1.339(3) C(2)-Re(1)-O(5) 175.09(11) C(3)-Re(1)-O(4) 176.93(11) C(1)-Re(1)-N(1) 170.68(11) O(5)-Re(1)-N(1) 75.19(7) Re(1)-C(1)-O(1) 176.9(3) C(2)-Re(1)-C(1) 88.41(13) O(5)-Re(1)-O(4) 83.39(7) N(1)-Re(1)-O(4) 81.99(8) C(3)-Re(1)-C(1) 86.41(14) The rhenium-centered bond angles C(2)-Re(1)-O(5) = 175.09(11) o , C(3)-Re(1)-O(4) = 176.93(6) o and C(1)-Re(1)-N(1) = 170.68(11) o deviated from the linearity supporting the distortion in 3 . Such distortion is furtherly supported by rhenium-centered bond angles C(2)-Re(1)-C(1) = 88.41(13) o , (5)-Re(1)-O(4) = 83.39(7) o , N(1)-Re(1)-O(4) = 81.99(8) o and C(3)-Re(1)-C(1) = 86.41(14) o which deviated from the orthogonality. The etpmdc − chelate coordinated to rhenium(I) center via one of the pyrimidinic nitrogen N(1) and carboxylate oxygen O(5) forming a bite angle of O(5)-Re(1)-N(1) = 75.19(7) o . For the reported similar pyrimidine derivatives complexes of rhenium(I), this angle was found 75.54(6) o and 75.14(5) ◦ [ 19 , 36 ]. The bond distance Re(1)-O(5) = 2.1489(19) Å in 3 agrees well with the reported R I -O distances in pyrimidine derivatives complexes of rhenium(I) based on the fac -[Re(CO) 3 ] + unit [ 19 , 36 ]. The Re − N(1) bond distance of 2.179(2) Å is compatible with the range 2.15 − 2.22 Å previously reported for rhenium(I) − N(imines) distances [ 11 , 37 ]. The average Re-C bond distances is 1.907(3) Å, and falls in the range 1.900(2)-1.928(2) Å reported for Re I -C distances [ 11 , 18 , 19 ]. The crystal packing diagram of 3 (Fig. S16) displays two asymmetric units in the unit cell and four intramolecular hydrogen bonds (blue dashed) which are typically C(8)-H(8)..O(6), C(10)-H(10A)..O(3), O(4)-H(4A)..O(3) and O(4)-H(4B)..O(6). Due to very low concentration of 99m Tc in solution which exists in nano-scale and similarity in the coordination chemistry of Re and Tc, the structural identity of 99m Tc-complexes is routinely confirmed by comparing their HPLC profiles with HPLC profiles of the homologous rhenium complexes, fully characterized by routine chemistry analytical techniques [ 19 ]. This consists of coinjecting 99m Tc complex with its homologous rhenium complex in the HPLC with UV/vis detection coupled with a γ-detector followed by comparison of retention times of the displayed γ-peaks of 99m Tc complex and UV peak of Re complex [ 19 ]. Therefore, the chemical similarity of 1 and 2 was assessed by coinjection of 10 µl of these complexes in the HPLC with UV/vis detection coupled with a γ-detector, and complex 1 was detected at R t = 11.7 min in UV (Fig. 3b) which coincides with the radiochemical peak of 2 detected at R t = 12.8 min in γ (Fig. 3a) confirming their structural similarity. The difference of 1.1 min for 1 and 2 is due to the UV/vis and γ-detectors separation and HPLC settings [ 19 ]. 3.2. Synthesis of (Et 3 NH) 2 [(µ-pmdc) 2 (Re(CO) 3 ) 2 (4) and [(µ-pmdc) 2 (Re(CO) 3 )( 99m Tc(CO) 3 )] 2− (5) Dimeric complex (Et 3 NH) 2 [(µ-pmdc) 2 (Re(CO) 3 ) 2 ] ( 4 ) was obtained from the reaction of H 2 pmdc with [Re(CO) 5 Br] in distilled water with addition of triethylamine (Et 3 N) as supporting base (Scheme 2 ). Complexes 4 is orange and it is soluble in polar solvents like water, ethanol and methanol, and exhibit a very low solubility in non-polar organic solvents. In the dimer 4 , pmdc − 2 coordinated to the fac -[M(CO) 3 ] + core as bidentate N,O-donor chelate, coordinating to the metal center via on of the pyrimidinic nitrogen and carboxylate-oxygen atoms, and the other carboxylate oxygen atom is coordinated to the other fac -[Re(CO) 3 ] + core. The reaction of [ 99m Tc(CO) 3 (OH 2 ) 3 ] + and [Re(CO) 5 Br] with H 2 pmdc led to the heterodinuclear 99m Tc/Re complex [(µ-pmdc) 2 (Re(CO) 3 )( 99m Tc(CO) 3 )] 2− ( 5 ) (Scheme 2 ), and it is parallelly formed with complexes 1 and 2 . Similar dimers of scandium(III) [ 15 ] and manganese(II) [ 32 ] with H 2 pmdc have been reported and pmdc 2− coordinated to the metal center as in complexes 4 and 5 . Complex 4 and 5 have shown good stability in aqueous solution. The previous studies revealed that the pKa value of organic acid ligands reflects its relative coordination ability to the metal ions, and determine the strength of the resulting metal-ligand bonds, and therefore the stability of metal-organic framework [ 38 ]. High value of pKa for organic acid ligands indicates its deprotonation weakness, and such ligand will mostly necessitate the supporting base to promote its deprotonation for coordinating to the metal ions [ 39 – 41 ]. The deprotonated organic acid ligand with high value of pKa strongly coordinates to the metal ions resulting in metal-organic framework with high stability [ 38 ]. The H 2 pmdc ligand is a weak acid with pKa value of 2.035, and therefore, its full deprotonation for forming dinuclear rhenium complex 4 necessitated triethyl amine (Et 3 N) as supporting base, and this complex has shown a significant stability. Similarly for forming heterodinuclear 99m Tc/Re complex 5 , the full deprotonation of H 2 pmdc has been supported by unidentified anionic base which is in place as a counterion of the cationic precursor complex [ 99m Tc(CO) 3 (OH 2 ) 3 ] + . In the infrared spectrum of 4 (Fig. S11), sharp bands at 2016 and 1875 cm − 1 are associated with fac -[Re(CO) 3 ] + units. In the 1 HNMR spectrum of 4 in D 2 O (Fig. S12), the CH 3 and CH 2 protons of Et 3 NH + counterions occur as triplet at 1.28 ppm and quartet at 3.20 ppm respectively. The singlet signals at 8.44 and 9.59 ppm are ascribed to H(3) and H(6) respectively. The 13 CNMR of 4 in D 2 O (Fig. S13) displayed signals at 8.04 and 46.64 ppm for CH 3 and CH 2 respectively for Et 3 NH + counterions. The carbon atoms of the coordinated pmdc 2− ligands occur at 120.33, 156.80, 160.48, 164.89, 168.80 and 173.41 ppm; while the carbona toms of the CO ligands are displayed at 193.00 and 195.59 ppm. Complex 4 was eluted in the UPLC and it was detected at 2.06 min (Fig. S10). The m/z peaks principally 872.91 [C 18 H 5 N 4 O 14 Re 2 ] − or [ 4 + H] − , 916.10 [C 20 H 10 N 5 O 14 Re 2 ] + or [ 4 + 3H + MeCN] + were detected in liquid chromatography-mass spectrometry (ESI-MS) analysis of 4 (Fig. S14 and Fig. S15) and furtherly confirmed its structure. The starting reagent used to synthesize compounds 1 , 3 and 4 is [Re(CO) 5 Br]. As the ligand H 2 pmdc was deprotonated and release H + ions in solution, the bromide ions (Br − ) reacted with H + ions from the deprotonated H 2 pmdc to form hydrobromic acid (HBr) as reaction byproduct. The HBr is inorganic acid and due to its high solubility in organic solvents, it was eliminated by several time washing of compounds 1 , 3 and 4 using organic solvents. In addition, the HBr has some degree of volatility and a particular quantity of it was eliminated by being volatilized in the air. Therefore, there is no Br maintained in the isolated materials of 1 , 3 and 4 [ 11 , 19 ]. The formation of rhenium(I) complexes from [Re(CO) 5 X] (X = Cl, Br) without the ligand deprotonation only leads to rhenium(I) complexes with Br − or Cl − ligand maintained in the isolated products [ 11 , 18 ]. Injection of 10 µl of the product from the reaction of [ 99m Tc(CO) 3 (OH 2 ) 3 ] + with H 2 pmdc and [Re(CO) 5 Br] in the HPLC with UV/vis detection coupled with a γ-detector displayed signals at retention times of 12.1 and 18.7 min in gamma with signal corresponding to the unreacted [ 99m Tc(CO) 3 (OH 2 ) 3 ] + and low intensity signal due to [ 99m TcO 4 ] − from the oxidation of 99m Tc I to 99m Tc VII (Fig. 4a). It has also shown two signals in UV at 11.2 and 18.4 min (Fig. 3b). The signal at R t = 11.2 min in UV (Fig. 4b) is due to the formation of [Re(CO) 3 (OH 2 )(Hpmdc)] ( 1 ) which coincides with the radiochemical signal at R t = 12.1 min in γ (Fig. 3a) suggesting the formation of [ 99m Tc(CO) 3 (OH 2 )(Hpmdc)] ( 2 ) as observed in Fig. 2 . The difference of 0.9 min for 1 and 2 is due to the detector separation and HPLC settings. The signal at R t = 18.4 min in UV (Fig. 4b) is due to the formation of heterodinuclear 99m Tc/Re complex [(µ-pmdc) 2 (Re(CO) 3 )( 99m Tc(CO) 3 )] 2− ( 5 ) which coincides with its radiochemical signal at R t = 18.7 min in γ (Fig. 4a), and the difference of 0.3 min is also due to the UV and γ-detectors separation and HPLC settings, and it was formed at yield of approximatively 35%. The obtained low yield of complex 5 (35%) is due to the fact that it was parallelly formed with complex 1 and 2 . In addition, unreacted quantity of [ 99m Tc(CO) 3 (OH 2 ) 3 ] + and its small quantity which has been oxidized to [ 99m TcO 4 ] − also partially contributed to such low yield of complex 5. The product at R t = 18.7 min in γ is [(µ-pmdc) 2 (Re(CO) 3 )( 99m Tc(CO) 3 )] 2− ( 5 ) rather than the dimer [(µ-pmdc) 2 ( 99m Tc(CO) 3 ) 2 ] 2− due to the fact that the low concentrations of 99m Tc makes the formation of dimeric 99m Tc species kinetically unlikely [ 19 ], and even if it is formed, it should not be detected in the UV as observed for [(µ-pmdc) 2 (Re(CO) 3 )( 99m Tc(CO) 3 )] 2− ( 5 ) (Fig. 5 b) due to its extremely low concentration. The formation of [(µ-pmdc) 2 (Re(CO) 3 )( 99m Tc(CO) 3 )] 2− ( 5 ) was furtherly confirmed by injecting its homologous non-radioactive dimer complex [(µ-pmdc) 2 (Re(CO) 3 ) 2 ] 2− ( 4 ) in the same HPLC which also displayed the UV signal at 18.4 min equivalent to that of [(µ-pmdc) 2 (Re(CO) 3 )( 99m Tc(CO) 3 )] 2− ( 5 ) (Fig. 4b). The observed similar retention times in UV for 4 and 5 confirms their structural identity. This is furtherly supported by the fact that the metals technetium and rhenium are located in the same position in the Periodic Table of elements, and have comparable atomic radii, and their homologous complexes should consequently display the same electronic properties and coordination parameters [ 11 , 42 ]. Further characterizations of heterometallic radiocomplex 5 are not applicable due to the above-mentioned reason of its low concentration in solution. A few numbers of heterodinuclear complexes containing Re and 99m Tc were previously reported in the literature. Recently, the highly stable complex [ 99m TcRe 3 (µ 3 -OH) 4 (CO) 12 ] has been reported, and it was obtained at 94% yield from the reaction of aqueous [ 99m Tc(CO) 3 (OH 2 ) 3 ] + with [Re 3 (µ 2 -OH) 3 (µ 3 -OH)(CO) 9 ] − [ 17 ]. The formation of 99m TcRe 3 (µ 3 -OH) 4 (CO) 12 ] was also achieved at 90% yield from the reaction of aqueous [ 99m Tc(CO) 3 (OH 2 ) 3 ] + with (NEt 4 ) 2 [ReBr 3 (CO) 3 ] [ 17 ]. The reaction of (E)-2-((m-tolylimino)methyl)phenol ligand with [ 99m Tc(CO) 3 (OH 2 ) 3 ] + and (NEt 4 ) 2 [ReBr 3 (CO) 3 ] in acetonitrile has been also studied, and led to the heterodinuclear 99m Tc/Re complex with exception stability [ 17 ]. Heterodinuclear 99m Tc/Re complex namely [Re(CO) 3 (bipy){(4-PyrIDA) 99m Tc(CO) 3 }] where 4-PyrIDA is N-carboxylato-N-(pyridin-4-ylmethyl)glycinate has been reported as the first example of 99m Tc/Re-based heterometallic assembly which could act as a potential bimodal optical/SPECT probe [ 43 ]. Such complex displayed similar retention time in the HPLC with its homologous dinuclear Re complex [Re(CO) 3 (bipy){(4-PyrIDA)Re(CO) 3 }] fully characterized by routine analytical techniques [ 43 ] confirming their structural identity as observed for complexes 4 and 5 reported in this study. Dinuclear Re and its homologous heterodinuclear 99m Tc/Re complexes based on the fac -[M(CO) 3 ] + core typically [Re(CO) 3 (pyta-COOMe){(4-pyrIDA)Re(CO) 3 }] and [Re(CO) 3 (pyta-COOMe){(4-pyrIDA) 99m Tc(CO) 3 }] where pyta-COOMe and PyrIDA are methyl 2-(4-(2-pyridyl)-[ 1 , 2 , 3 ]triazol-1-yl)acetate and 2,2'-((pyridin-4-ylmethyl)azanediyl)diacetate) respectively have been also reported [ 44 ]. Heterodinuclear 99m Tc/Re complex [Re(CO) 3 (pyta-COOMe){(4-pyrIDA) 99m Tc(CO) 3 }] was the first reported example of a functionalized dual fluorescent/radiolabeled imaging agent, and it was characterized by comparing its HPLC profile with the HPLC profile of its homologous and fully characterized dinuclear Re complex Re(CO) 3 (pyta-COOMe){(4-pyrIDA)Re(CO) 3 }] [ 44 ]. Both complexes displayed similar retention times in the HPLC as observed for complexes 4 and 5 reported in this study confirming their structural identity [ 44 ]. Multinuclear complexes are advantageous in medicinal inorganic chemistry as they may target more than one unit in the body, and can be delivered by more than one bioactive moiety [ 17 ]. In addition, the possibility of combining radiometal agents with cytotoxicity and imaging properties gave rise to a new concept of molecule-based theranostic radiopharmaceuticals with a specific amount of therapeutic and imaging agents [ 17 ]. In this way, the existence of similar coordination chemistry between Re and Tc makes possible to afford stable heterodinuclear 99m Tc/ 186/188 Re complexes with 99m Tc and 186/188 Re showing similar electronic properties, and such complexes act as theranostic radiopharmaceuticals displaying imaging and therapeutic properties [ 45 ]. Therefore, heterodinuclear 99m Tc/Re complex [(µ-pmdc) 2 (Re(CO) 3 )( 99m Tc(CO) 3 )] 2− ( 5 ) reported in this study will be a model for future design of theranostic radiopharmaceuticals combining imaging and therapy. 4. Conclusion In this work, monomeric and dimeric complexes of the fac -[M(CO) 3 ] + (M = Re and 99m Tc) core with pyrimidine-4,6-dicarboxylic acid (H 2 pmdc) ligand have been synthesized and characterized. These complexes are the model for future design of radiopharmaceuticals. The structural identification of 99m Tc-complexes is challenge due to its very low concertation in solution. As previously reported in the literature, the structural identity of 99m Tc-complexes reported in this study was achieved by comparing their HPLC profiles with HPLC profiles of their homologous rhenium complexes, fully characterized by routine chemistry analytical techniques. The existence of very low concentrations of 99m Tc in solution also make the color of its complexes not detectable, and they are always colorless, and it is the reason why the solution of complexes 2 and 5 did not show any color. Although the coordination mode of H 2 pmdc in 1–4 was previously reported for other transition metal ions, compounds 1–4 are the first reported complexes of H 2 pmdc with rhenium and technetium metals. In future, the reported heterodinuclear 99m Tc/Re complex 5 will extend the theranostic modalities beyond mononuclear complexes. For further studies, our research efforts will be extended by reacting H 2 pmdc with [ 99 TcCl 3 (CO) 3 )] 2− for ensuring that 99 Tc complexes homologous to 1–4 will be formed. Furthermore, a mixture of [ 99 TcCl 3 (CO) 3 )] 2− with [ 99m Tc(CO) 3 (OH 2 ) 3 ] + and [ReBr(CO) 5 ] with [ 99 TcCl 3 (CO) 3 )] 2− will be reacted with H 2 pmdac ligand for ensuring that the heterodinuclear 99m Tc/ 99 Tc and 99 Tc/Re complexes respectively similar to 5 will be obtained. In addition, aqueous [ 99m Tc(CO) 3 (OH 2 ) 3 ] + and [ReBr(CO) 5 ] will be reacted with the ligands analogous to H 2 pmdc typically pyrimidine-4,6-diyldimethanol, hexahydropyrimidine-4,6-dicarboxylic acid and 1,2,3,4-tetrahydropyrimidine-4,6-dicarboxylic acid for ensuring that they will behave as H 2 pmdc. Declarations Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Author Contribution JM: design the manuscript and synthesis and analysis of complexesGH: Writing Introduction and contribute crystal data interpretation and records.JS: Contributes in the interpretation of 1HNMR and HPLC data.TM: Contributes in Interpretation of IR and ESI-MS data and review of entire manuscript.JN: Contributes Literature reported in this manuscript as well as 13CNMR data interpretationTU: Contributes in writing the manuscript.TM: Edit the entire manuscript and provide input in interpretation of NMR and ESI-MS data.OB: He is the one who measured and provide data of the crystal structure reported in this manuscript.GB: Provide ideas in purification of the reported complexes and reviewed the entire manuscript. Acknowledgement Prof. Alberto Roger, Henrik Braband, University of Zurich and Research Group under Prof. Alberto Roger are strongly acknowledged. References C.R. Nathan Rose, S. Stanley Ng, J. Mecinovic, B.M.R. Lienard, S.H. Bello, Z. Sun, M. A. McDonough, U. 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Huang, An unusual double T5(2) water tape trapped in silver(I) coordination polymer hosts: influence of the solvent on the assembly of Ag(I)-4,4′-bipyridine chains with trans -cyclohexanedicarboxylate and their luminescent properties, Dalton Trans. 41 , 12872–12881 (2012), https://doi.org/10.1039/C2DT31847D. L.N. Dong, Y. Tian, X. Li and Y. Jiang, 3-D frameworks assembled by lanthanide dimers with 1,4-cyclohexanedicarboxylic acid and 1,10-phenanthroline via hydrogen bonds and π–π stacking interactions, J. Coord. Chem. 63 , 2088–2096 (2010), https://doi.org/10.1080/00958972.2010.498911. K. P. Rao, A. Thirumurugan, C. N. R. Rao, Lamellar and Three-Dimensional Hybrid Compounds Formed by Cyclohexene- and Cyclohexanedicarboxylates of Pb, La, and Cd, Chem. Eur. J. 13 , 3193–3201 (2007), https://doi.org/10.1002/chem.200600966. V.Y. Kukushki, Metal-ion mediated deoxygenation of sulfoxides, Coord. Chem. Rev. 139 , 375-407 (1995), https://doi.org/10.1016/0010-8545(94)01116-S. A. Boulay, M. Artigau, Y. Coulais, C. Picard, B. Mestre-Voegtl, E. Benoist, First dinuclear Re/Tc complex as a potential bimodal Optical/SPECT molecular imaging agent, Dalton Trans. 40 , 6206–6209 (2011), https://doi.org/10.1039/C0DT01397H. F. Alison, C. Auzanneau, V. Le Morvan, C. Galaup, S.G. Hannah, L. Marty, A. Boulay, M. Artigau, B. Mestre-Voegtlé, N. Leygue, C. Picard, Y. Coulais, J. Robert, E. Benoist, A functionalized heterobimetallic 99m Tc/Re complex as a potential dual-modality imaging probe: synthesis, photophysical properties, cytotoxicity and cellular imaging investigations, Dalton Trans. 43 , 439–450 (2014), https://doi.org/10.1039/C3DT51968F. C. Mamat, C. Jentschel, M. Köckerling, J. Steinbach, Strategic Evaluation of the Traceless Staudinger Ligation for Radiolabeling with the Tricarbonyl Core, Molecules 26 , 6629 (2021), https://doi.org/10.3390/molecules26216629. Schemes Schemes 1 and 2 are available in the Supplementary Files section Additional Declarations No competing interests reported. Supplementary Files ManuscriptSIApril.docx Scheme1.png Scheme 1. Aqueous synthesis of monomeric rhenium and technetium complexes of pyrimidine-4,6-dicarboxylic acid (H 2 pmdc) based on the fac -[M(CO) 3 ] + core. Scheme2.png Scheme 2. Aqueous synthesis of dimeric rhenium complex (4) and its homologous heterobimetallic rhenium and technetium-99m complex (5) of pyrimidine-4,6-dicarboxylic acid (H 2 pmdc) based on the fac -[M(CO) 3 ] + core. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4381286","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":301557161,"identity":"207e8704-af04-4eca-8bb5-479ecff92ecf","order_by":0,"name":"Janvier Mukiza","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYBACxgYgkQBmsjEcYGCwAYk1HiBFSxpYDK8WJMAGIg6DmXi1MLefPSbxoOIeg+6MtMSDP2rO261tPwy0pcYmGqfDevLSJBLOFDOY3Ug7cEDi2O3kbWcSgVqOpeU24PRLjrFBYlsCUEt6wwEDttvJZgeAWhgbDuPW0v8GqOUfVEvCv3PJZucfEtAyI8fwQWJDAsRhB9sO2JndIGTLjDeGDxKOJfCYnXmWcLCxLznB7AbQlgQ8fjHszzEABlSCnNnxNOOPP77Z2ZudT3/44EONDW4tUAkemEAiWCABh3IQkEcXsMejeBSMglEwCkYoAAADKGnfEDi2ugAAAABJRU5ErkJggg==","orcid":"","institution":"University of Zurich","correspondingAuthor":true,"prefix":"","firstName":"Janvier","middleName":"","lastName":"Mukiza","suffix":""},{"id":301557162,"identity":"182118bc-0318-48f7-87d7-cd0a2f9a91ea","order_by":1,"name":"Gratien Habarurema","email":"","orcid":"","institution":"University of Rwanda-College of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Gratien","middleName":"","lastName":"Habarurema","suffix":""},{"id":301557163,"identity":"ea87f3f6-12e5-4ca7-b551-dd0ee791b3c1","order_by":2,"name":"Jurdas Sezirahiga","email":"","orcid":"","institution":"Rwanda Food and Drugs Authority","correspondingAuthor":false,"prefix":"","firstName":"Jurdas","middleName":"","lastName":"Sezirahiga","suffix":""},{"id":301557164,"identity":"44e80d85-91c0-468e-af92-1e1a8a419f3b","order_by":3,"name":"Theonille Mukabagorora","email":"","orcid":"","institution":"University of Rwanda","correspondingAuthor":false,"prefix":"","firstName":"Theonille","middleName":"","lastName":"Mukabagorora","suffix":""},{"id":301557165,"identity":"da087625-2e28-414e-b8a8-26b6b3e067a9","order_by":4,"name":"Jean Bosco Nkuranga","email":"","orcid":"","institution":"University of Rwanda-College of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Jean","middleName":"Bosco","lastName":"Nkuranga","suffix":""},{"id":301557166,"identity":"3028a7bf-b8ae-411e-b777-343be5e4c75d","order_by":5,"name":"Tite Uwambajineza","email":"","orcid":"","institution":"Rwanda Food and Drugs Authority","correspondingAuthor":false,"prefix":"","firstName":"Tite","middleName":"","lastName":"Uwambajineza","suffix":""},{"id":301557167,"identity":"815d088a-6e0f-45da-ae0c-032cccb61cdd","order_by":6,"name":"Theoneste Muyizere","email":"","orcid":"","institution":"University of Chinese Academy of Sciences","correspondingAuthor":false,"prefix":"","firstName":"Theoneste","middleName":"","lastName":"Muyizere","suffix":""},{"id":301557168,"identity":"32476eeb-69e7-458f-a100-51c84671566b","order_by":7,"name":"Olivier Blacque","email":"","orcid":"","institution":"University of Zurich","correspondingAuthor":false,"prefix":"","firstName":"Olivier","middleName":"","lastName":"Blacque","suffix":""},{"id":301557169,"identity":"424934f5-cb26-4e1c-b4be-32c81e6ebc33","order_by":8,"name":"Gervais Baziga","email":"","orcid":"","institution":"Rwanda Food and Drugs Authority","correspondingAuthor":false,"prefix":"","firstName":"Gervais","middleName":"","lastName":"Baziga","suffix":""}],"badges":[],"createdAt":"2024-05-07 08:05:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4381286/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4381286/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":56564119,"identity":"9cecc798-63c1-4d57-825a-b85e05b886c1","added_by":"auto","created_at":"2024-05-15 22:42:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":8246,"visible":true,"origin":"","legend":"\u003cp\u003eStructure of pyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) ligand used in this study\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4381286/v1/8d99dcb9a7b51974105a372e.png"},{"id":56564120,"identity":"ef4123a4-921b-4bd8-9f21-f074d16d4c27","added_by":"auto","created_at":"2024-05-15 22:42:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":99232,"visible":true,"origin":"","legend":"\u003cp\u003eMolecular structure of \u003cstrong\u003e3 \u003c/strong\u003ewith the thermal ellipsoid showing 50% probability level and atoms labelling\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4381286/v1/5171a64485e6617e278b2729.png"},{"id":56564122,"identity":"8e91fbb2-a2bb-4cc2-88b4-749145b2710d","added_by":"auto","created_at":"2024-05-15 22:42:28","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":57363,"visible":true,"origin":"","legend":"\u003cp\u003eHPLC traces of \u003cstrong\u003e2\u003c/strong\u003e (\u003cstrong\u003ea\u003c/strong\u003e) and the corresponding peak of \u003cstrong\u003e1\u003c/strong\u003e (\u003cstrong\u003eb\u003c/strong\u003e) as received by co-injection of \u003cstrong\u003e1\u003c/strong\u003e and \u003cstrong\u003e2 \u003c/strong\u003ein the HPLC with UV/vis detection coupled with γ-detector.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4381286/v1/cde2e8dded67c8db1e9089c4.png"},{"id":56564626,"identity":"556bec05-a370-4fb2-92f2-06842b9a76bd","added_by":"auto","created_at":"2024-05-15 22:50:28","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":69852,"visible":true,"origin":"","legend":"\u003cp\u003eHPLC traces of the product from the reaction of [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e with H\u003csub\u003e2\u003c/sub\u003epmdc and [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr]\u0026nbsp; in γ (a) and the corresponding signals in UV (b) as received by injection in the HPLC with UV/vis detection coupled with γ-detector.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4381286/v1/c1880e3b3a44342f6f50d65d.png"},{"id":56564123,"identity":"3bda94b2-5850-4d33-9b88-66d7fd5728fe","added_by":"auto","created_at":"2024-05-15 22:42:28","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":120469,"visible":true,"origin":"","legend":"\u003cp\u003eOverlay of the UV of the product from the reaction of [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e with H\u003csub\u003e2\u003c/sub\u003epmdc and [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr] (Blue)\u0026nbsp; and the UV of (Et\u003csub\u003e3\u003c/sub\u003eNH)\u003csub\u003e2\u003c/sub\u003e[(µ-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e] (\u003cstrong\u003e4\u003c/strong\u003e) \u0026nbsp;\u0026nbsp;(Orange) measured in the same HPLC UV/vis detection coupled with γ-detector, showing complexes \u003cstrong\u003e4\u003c/strong\u003e and \u003cstrong\u003e5 \u003c/strong\u003ewith similar retention times in\u0026nbsp; UV.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-4381286/v1/bba335f9a4c598fbf4749647.png"},{"id":57377497,"identity":"7f9df735-5a06-4750-87a6-45686b572a05","added_by":"auto","created_at":"2024-05-29 23:46:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1551064,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4381286/v1/3a49501b-addf-4d6c-9d0a-4464443780de.pdf"},{"id":56564124,"identity":"99d54173-1cbf-414a-b0c9-6dc4bd71662b","added_by":"auto","created_at":"2024-05-15 22:42:28","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1068909,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptSIApril.docx","url":"https://assets-eu.researchsquare.com/files/rs-4381286/v1/6eaf514466535ea59f5879fc.docx"},{"id":56564121,"identity":"4afcf950-3055-4c80-b75c-0917ffbd1898","added_by":"auto","created_at":"2024-05-15 22:42:28","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":58074,"visible":true,"origin":"","legend":"\u003cp\u003eScheme 1. Aqueous synthesis of monomeric rhenium and technetium complexes of pyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) based on the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e core.\u003c/p\u003e","description":"","filename":"Scheme1.png","url":"https://assets-eu.researchsquare.com/files/rs-4381286/v1/eef9db7ae4f61eb5b46ff3e6.png"},{"id":56564126,"identity":"585149f5-adcd-4356-b6d7-5ca7ae187324","added_by":"auto","created_at":"2024-05-15 22:42:28","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":74066,"visible":true,"origin":"","legend":"\u003cp\u003eScheme 2. Aqueous synthesis of dimeric rhenium complex (\u003cstrong\u003e4\u003c/strong\u003e) and its homologous heterobimetallic rhenium and technetium-99m complex (\u003cstrong\u003e5\u003c/strong\u003e) of pyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) based on the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e core.\u003c/p\u003e","description":"","filename":"Scheme2.png","url":"https://assets-eu.researchsquare.com/files/rs-4381286/v1/92349889ca81f49bbeb758b7.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eMonomeric and dimeric complexes of pyrimidine-4,6-dicarboxylic acid with organometallic fac-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e (M = Re and \u003csup\u003e99m\u003c/sup\u003eTc) core as radiopharmaceutical probes\u003c/p\u003e","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003ePyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) is naturally occurring heterocyclic compound, and it is found in many organisms as building block of biological molecules, and involved in different metabolic pathways [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. It is involved in the synthesis of purines and pyrimidines bases, which are the building blocks of DNA and RNA, and regulation of the Krebs cycle during glucose metabolism [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In addition, H\u003csub\u003e2\u003c/sub\u003epmdc is of interest as it is potentially applied in the synthesis of a variety of compounds, including antibiotics, antivirals, and other drugs [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Due to its large number of donor atoms and flexibility as small molecule, H\u003csub\u003e2\u003c/sub\u003epmdc ligand has shown a remarkable capacity in the development of coordination chemistry [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The diversity of its coordination mode to metal ions is reflected in the variety of known and stable metal complexes with this ligand, which vary from monomers to ligand-bridged dimers and multimers [\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Furthermore, the H\u003csub\u003e2\u003c/sub\u003epmdc contains two carboxylic acid groups and two imine nitrogens which is advantage in the coordination chemistry since it can be easily functionalized and derivatized [\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRhenium (Re) and technetium (Tc) are located in Group VII on the Periodic Table of elements and have comparable atomic radii, and consequently display similar coordination chemistry [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Therefore, the chemistry of rhenium is used for modelling one of technetium [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Due to their location in the middle of the d-block of transition metals, Re and Tc exhibit the properties of both early and later transition metals [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and display the oxidation state which varies from \u0026minus;\u0026thinsp;1 to +\u0026thinsp;7 [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The chemistry of Re and Tc is continuing to attract the researchers due to the potential application of these elements in nuclear medicine [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Rhenium radioisotopes \u003csup\u003e186/188\u003c/sup\u003eRe are γ and β-emitters and applied in therapeutic nuclear medicine, while technetium radioisotope \u003csup\u003e99m\u003c/sup\u003eTc is γ-emitter and applied in nuclear medicine imaging procedures [\u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The similarity in the coordination chemistry of Re and Tc makes possible to share the same biodistribution partners in the body for analogous radiopharmaceuticals based on these elements, and enable the monitoring of their biodistribution using the same γ-ray camera [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOrganometallic \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e (M\u0026thinsp;=\u0026thinsp;Re and Tc) core dominates the chemistry of rhenium(I) and technetium(I), and it is well known by its small size, three vacant coordination sites and three flexible and facially arranged CO ligands [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e (M\u0026thinsp;=\u0026thinsp;Re and Tc) core displays d\u003csup\u003e6\u003c/sup\u003e and low-spin electronic configuration, and its complexes are characterized by a distorted octahedral geometry and high kinetic and thermodynamic stability [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. It is routinely coordinate to different chelating ligands leading to the complexes which structurally vary from monomers to ligand-bridged multimers, and even from metal-metal multiply bonded multimers to clusters [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Organometallic complexes based on the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e (M\u0026thinsp;=\u0026thinsp;Re and Tc) core have attracted much attention due particularly to their possible application in the development of radiopharmaceuticals which involve imaging \u003csup\u003e99m\u003c/sup\u003eTc and therapeutic \u003csup\u003e186/188\u003c/sup\u003eRe compounds [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Due to the small size of octahedral complexes based on the the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e (M\u0026thinsp;=\u0026thinsp;Re and Tc) core considerably to the octahedral or square-pyramidal complexes of the corresponding metals in higher oxidation states, they are considered less likely to impact important characteristics of bio-molecules to which they are conjugated to [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePyrimidine derivatives with electron-rich sp\u003csup\u003e2\u003c/sup\u003e-hybridized nitrogen atoms have been identified as convenient ligands to stabilize the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e (M\u0026thinsp;=\u0026thinsp;Re and Tc) core [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Despite their variety of possible applications, rhenium and technetium complexes based on the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e core (M\u0026thinsp;=\u0026thinsp;Re and Tc) with pyrimidine derivative ligands have not been extensively explored [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], and few examples have been reported. The \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e core (M\u0026thinsp;=\u0026thinsp;Re and Tc) complexes with pyrimidine nucleoside derivatives have been reported and provided a convenient platform for drugs development [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Recently, complexes of the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e (M\u0026thinsp;=\u0026thinsp;Re and \u003csup\u003e99\u003c/sup\u003eTc/\u003csup\u003e99m\u003c/sup\u003eTc) core with pyrimidine based ligands typically orotic acid and its derivatives have been reported [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The current study highlights on the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e (M\u0026thinsp;=\u0026thinsp;Re and \u003csup\u003e99m\u003c/sup\u003eTc) core complexes with pyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) which are the model for future design of imaging, therapeutic and theranostic radiopharmaceuticals.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe reported rhenium complexes were characterized by using \u003csup\u003e1\u003c/sup\u003eHNMR, \u003csup\u003e13\u003c/sup\u003eCNMR, IR and ESI-MS, and complex \u003cb\u003e3\u003c/b\u003e was additionally characterized by using single crystal X-ray crystallography. Identity of the reported monomeric rhenium and technetium complexes was confirmed by coinjection in the same HPLC with UV/Vis detection coupled with a γ-detector followed by comparison of retention times for UV- and γ-signals. Evidence of the formation of heterodinuclear \u003csup\u003e99m\u003c/sup\u003eTc/Re complex \u003cb\u003e5\u003c/b\u003e was assessed by the comparison of its HPLC profile with the HPLC profile of its homologous rhenium dimer complex \u003cb\u003e4\u003c/b\u003e fully characterized by routine chemistry analytical techniques.\u003c/p\u003e"},{"header":"2. Experimental","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Materials and instrumentation\u003c/h2\u003e \u003cp\u003e \u003cstrong\u003eCaution\u003c/strong\u003e \u003cp\u003e \u003csup\u003e99m\u003c/sup\u003eTc is weak γ-emitters. All experiments involving \u003csup\u003e99m\u003c/sup\u003eTc were done in the laboratories approved for working with the low-level radioactive materials. All reactions and solution preparations were carried out under an inert N\u003csub\u003e2\u003c/sub\u003e atmosphere. [\u003csup\u003e99m\u003c/sup\u003eTcO4]\u003csup\u003e\u0026minus;\u003c/sup\u003e was eluted from a \u003csup\u003e99\u003c/sup\u003eMo / \u003csup\u003e99m\u003c/sup\u003eTc Ultratechnekow FM generator from Mallinckrodt Schweiz AG. The [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr] and pyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) were obtained from the Sigma Aldrich. The \u003csup\u003e99m\u003c/sup\u003eTc precursor complex [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e was obtained from the reduction of [\u003csup\u003e99m\u003c/sup\u003eTcO\u003csub\u003e4\u003c/sub\u003e]\u003csup\u003e\u0026minus;\u003c/sup\u003e according to the reported literature method [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003c/p\u003e \u003cp\u003eThe purity of the reported rhenium complexes was confirmed by Ultraperformance Liquid Chromatographic (UPLC) with a Nucleosil C-18 column (100 \u0026Aring;, 5 \u0026micro;m, 250 \u0026times; 4 mm) which was eluted with a flow rate of 0.5 ml min\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, using 0.1% trifluoro-acetic acid (TFA) in H\u003csub\u003e2\u003c/sub\u003eO (solvent A) and acetonitrile (solvent B). \u003csup\u003e1\u003c/sup\u003eHNMR and \u003csup\u003e13\u003c/sup\u003eCNMR spectra were recorded on Bruker Advance 400 and 500 MHz NMR spectrometer. Deuterated methanol (CD\u003csub\u003e3\u003c/sub\u003eOD) and water (D\u003csub\u003e2\u003c/sub\u003eO) were used as NMR solvents and the peak positions were obtained relatively to tetramethylsilane (SiMe\u003csub\u003e4\u003c/sub\u003e). The infrared spectra were recorded on a Perkin-Elmer FT-IR Spectrum Two spectrometer, using ATR technique, and applied as neat samples. HPLC analyses were performed on a Merck Hitachi LaChrom L 7100 pump coupled to a Merck Hitachi LaChrom L7455 photo diode array. UV/Vis detection was performed at 250 nm. The detection of radioactive \u003csup\u003e99m\u003c/sup\u003eTc complexes was performed with Berthold Technologies Flowstar LB513 radiodetectors equipped with YG/BGO cells, respectively. The radiodetectors were coupled to the HPLC systems. Separations were achieved on a Macherey-Nagel C18 reversed-phase column (EC-250 / 3 Nucleosil 100-5 C18) using gradients of CF\u003csub\u003e3\u003c/sub\u003eCOOH (0.1% in H\u003csub\u003e2\u003c/sub\u003eO, solvent A) and MeOH (solvent B). Comparison of the HPLC retention times for the \u003csup\u003e99m\u003c/sup\u003eTc compounds with the corresponding Re compounds confirms the complexes\u0026rsquo; identity. Liquid chromatography (ESI-MS) was analysed using BrukerEsquire HCT (ESI) instrument. The elemental analyses for carbon, hydrogen and nitrogen were performed on a Vario EL (ElementarAnalysensystem GmbH) instrument.\u003c/p\u003e \u003cp\u003eSingle-crystal X-ray diffraction data was collected at 160(1) K on a Rigaku OD XtaLAB Synergy, Dualflex, Pilatus 200K diffractometer using a single wavelength X-ray source (Mo Kα radiation: λ = 0.71073 \u0026Aring;) [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] from a micro-focus sealed X-ray tube and an Oxford liquid-nitrogen Cryostream cooler. The selected suitable single crystal was mounted using polybutene oil on a flexible loop fixed on a goniometer head and immediately transferred to the diffractometer. Pre-experiment, data collection, data reduction and analytical absorption correction [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] were performed with the program suite \u003cem\u003eCrysAlisPro 20\u003c/em\u003e [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Using \u003cem\u003eOlex2\u003c/em\u003e, [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] the structure was solved with the SHELXT [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] small molecule structure solution program and refined with the \u003cem\u003eSHELXL 2018/3\u003c/em\u003e program package [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] by full-matrix least-squares minimization on F [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. \u003cem\u003ePLATON\u003c/em\u003e [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] was used to check the result of the X-ray analysis. For more details about the data collection and refinement parameters, see the CIF file.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Synthesis of [Re(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(Hpmdc)] (1)\u003c/h2\u003e \u003cp\u003e[Re(CO)\u003csub\u003e5\u003c/sub\u003eBr] (34.92 mg, 0.086 mmol) and pyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) (14.45 mg, 0.086 mmol) were added to 10 cm\u003csup\u003e3\u003c/sup\u003e of distilled water. The resulting colorless mixture was heated under refluxed for 6 hours, giving an orange-yellow solution, which was filtered after being cooled to room temperature. No precipitate was obtained. The solvent was removed by evaporation and the yellow-orange precipitate of \u003cb\u003e1\u003c/b\u003e was purified by washing it several times by dichloromethane and diethylether and dried under vacuum. Yield (\u003cb\u003e1\u003c/b\u003e)\u0026thinsp;=\u0026thinsp;65% (25.45 mg). Anal. Calcd. for C\u003csub\u003e9\u003c/sub\u003eH\u003csub\u003e5\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e8\u003c/sub\u003eRe (Mol. Wt. = 455.35 g/mol): C, 23.74; H, 1.11; N, 6.15. Found: C, 23.77; H, 1.10; N, 6.13. IR (νmax/cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e): ѵ(O\u0026thinsp;\u0026minus;\u0026thinsp;H) 3225, 3110; ѵ(C\u0026thinsp;\u0026equiv;\u0026thinsp;O)) 2042, 1908, 1932; ѵ(C\u0026thinsp;=\u0026thinsp;O)) 1712; ѵ(C\u0026thinsp;=\u0026thinsp;N) 1636, 1599. \u003csup\u003e1\u003c/sup\u003eHNMR (295K, D\u003csub\u003e2\u003c/sub\u003eO, 400MHz) δ ppm: 8.56 (s, 1H, H(3)), 9.66 (s, 1H, H(6)). \u003csup\u003e13\u003c/sup\u003eCNMR (295K, CD\u003csub\u003e3\u003c/sub\u003eOD, 125MHz) δ ppm: 122.76 (C(3)), 159.52 (C(6)), 162.97 (C(4)), 167.41 (C(2)), 171.40 (C(b)), 175.89 (C(a)), 194.96, 198.01 (CO). ESI-MS (m/z): [C\u003csub\u003e9\u003c/sub\u003eH\u003csub\u003e6\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e8\u003c/sub\u003eRe]\u003csup\u003e+\u003c/sup\u003e or [\u003cb\u003e1\u003c/b\u003e\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e, calculated: 456.97, found: 457.03; [C\u003csub\u003e9\u003c/sub\u003eH\u003csub\u003e4\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e7\u003c/sub\u003eRe]\u003csup\u003e+\u003c/sup\u003e or [\u003cb\u003e1\u003c/b\u003e-H\u003csub\u003e2\u003c/sub\u003eO\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e, calculated: 438.96, found: 439.06, [C\u003csub\u003e11\u003c/sub\u003eH\u003csub\u003e7\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e7\u003c/sub\u003eRe]\u003csup\u003e+\u003c/sup\u003e or [\u003cb\u003e1\u003c/b\u003e\u0026thinsp;+\u0026thinsp;MeCN\u0026thinsp;+\u0026thinsp;H-H\u003csub\u003e2\u003c/sub\u003eO]\u003csup\u003e+\u003c/sup\u003e, calculated: 479.98, found: 479.99. UPLC (retention time min.): 1.80.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Synthesis of [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(Hpmdc)] (2)\u003c/h2\u003e \u003cp\u003e300 \u0026micro;l of [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e in water were mixed with 300\u0026micro;l of 0.01M aqueous solution of pyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) in vial which was sealed and flushed with N\u003csub\u003e2\u003c/sub\u003e for 15 min. The mixture was heated at 80\u003csup\u003eo\u003c/sup\u003eC for 30 min. The solution was brought to r.t. Injection of the solution in the HPLC equipped by gamma and UV detectors displayed the product with a radiochemical yield\u0026thinsp;\u0026gt;\u0026thinsp;99%. Heating under microwave at the same temperature gave the product in approximately the same yields. The nature of complex \u003cb\u003e2\u003c/b\u003e was identified by coinjection with [Re(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(Hpmdc)] (\u003cb\u003e1\u003c/b\u003e) in the same HPLC equipped with UV/Vis detection coupled with γ-detector followed by comparison of retention time.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Synthesis of [Re(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(etpmdc)] (3)\u003c/h2\u003e \u003cp\u003e[Re(CO)\u003csub\u003e5\u003c/sub\u003eBr] (34.92 mg, 0.086 mmol) and pyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) (14.45 mg, 0.086 mmol) were added to 10 cm\u003csup\u003e3\u003c/sup\u003e of ethanol. The resulting colorless mixture was heated under refluxed for 6 hours, giving orange solution, which was filtered after being cooled to room temperature, giving an orange precipitate of [Re(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(etpmdc)] (\u003cb\u003e3\u003c/b\u003e). Compound \u003cb\u003e3\u003c/b\u003e was purified by washing it several times by ethanol and diethylether, and dried under vacuum. Orange-yellow crystals suitable for X-ray diffraction analysis were obtained by the slow evaporation of the filtrate over 4 weeks at room temperature. The crystals of 3 have been also grown from recrystallization of precipitate of \u003cb\u003e3\u003c/b\u003e in ethanol with 20% of dichloromethane in 3 weeks by the slow evaporation of solvents at room temperature. Yield (1)\u0026thinsp;=\u0026thinsp;87% (31.18 mg). Anal. Calcd. for C\u003csub\u003e11\u003c/sub\u003eH\u003csub\u003e9\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e8\u003c/sub\u003eRe (Mol. Wt. = 483.41 g/mol): C, 27.33; H, 1.88; N, 5.80. Found: C, 27.29; H, 1.85; N, 5.77. IR (νmax/cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e): ѵ(O\u0026thinsp;\u0026minus;\u0026thinsp;H) 3364; ѵ(C\u0026thinsp;\u0026equiv;\u0026thinsp;O)) 1873, 1883, 2015; ѵ(C\u0026thinsp;=\u0026thinsp;O)) 1689; ѵ(C\u0026thinsp;=\u0026thinsp;N) 1585, 1581; ѵ(C\u0026thinsp;\u0026minus;\u0026thinsp;H) 3089, 3091. \u003csup\u003e1\u003c/sup\u003eHNMR (295K, CD\u003csub\u003e3\u003c/sub\u003eOD, 400MHz) δ ppm: 1.45 (t, 3H, CH\u003csub\u003e3\u003c/sub\u003e), 4.52 (q, 2H, CH\u003csub\u003e2\u003c/sub\u003e), 4.07 (s, 2H, H\u003csub\u003e2\u003c/sub\u003eO), 8.61 (s, 1H, H(3)), 9.64 (s, 1H, H(6)). \u003csup\u003e13\u003c/sup\u003eCNMR (295K, CD\u003csub\u003e3\u003c/sub\u003eOD, 125MHz) δ ppm: 14.85 (CH\u003csub\u003e3\u003c/sub\u003e), 64.88 (CH\u003csub\u003e2\u003c/sub\u003e), 123.13 (C(3)), 160.72 (C(6)), 160.76 (C(4)), 162.34 (C(2)), 164.30 (C(b)), 173.79 (C(a)), 197.37, 197.05, 193.94 (CO). ESI-MS (m/z): [C\u003csub\u003e11\u003c/sub\u003eH\u003csub\u003e8\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e7\u003c/sub\u003eRe]\u003csup\u003e+\u003c/sup\u003e or [\u003cb\u003e3\u003c/b\u003e-H\u003csub\u003e2\u003c/sub\u003eO\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e, calculated: 466.99, found: 467.21, [C\u003csub\u003e13\u003c/sub\u003eH\u003csub\u003e11\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e7\u003c/sub\u003eRe]\u003csup\u003e+\u003c/sup\u003e or [\u003cb\u003e3\u003c/b\u003e\u0026thinsp;+\u0026thinsp;MeCN\u0026thinsp;+\u0026thinsp;H-H\u003csub\u003e2\u003c/sub\u003eO]\u003csup\u003e+\u003c/sup\u003e, calculated: 508.02, found: 508.15.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Synthesis of (Et\u003csub\u003e3\u003c/sub\u003eNH)\u003csub\u003e2\u003c/sub\u003e[(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e] (4)\u003c/h2\u003e \u003cp\u003ePyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) (20.67 mg, 0.123 mmol) was added to [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr] (49.95 mg, 0.123 mmol) in 10 cm\u003csup\u003e3\u003c/sup\u003e of distilled water and 3 drops of triethylamine (Et\u003csub\u003e3\u003c/sub\u003eN). The resulting colourless mixture was refluxed for 24 hours, giving an orange solution, which was filtered after being cooled to room temperature. No precipitate was formed; the filtrate was removed giving an orange precipitate of \u003cb\u003e4\u003c/b\u003e which was purified by washing it several times by dichloromethane and diethylether. Yield\u0026thinsp;=\u0026thinsp;85% (56.30 mg). Anal. Calcd. for C\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e36\u003c/sub\u003eN\u003csub\u003e6\u003c/sub\u003eO\u003csub\u003e14\u003c/sub\u003eRe\u003csub\u003e2\u003c/sub\u003e (Mol. Wt. = 1077.06 g/mol): C, 33.45; H, 3.37; N, 7.80. Found: C, 33.41; H, 3.32; N, 7.78. IR (νmax/cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e): ѵ(C\u0026thinsp;\u0026equiv;\u0026thinsp;O)), 2016, 1875; ѵ(C\u0026thinsp;=\u0026thinsp;O) 1646, ѵ(C\u0026thinsp;=\u0026thinsp;N) 1599, 1538, ѵ(C-H) 2988. \u003csup\u003e1\u003c/sup\u003eH-NMR (295K, D\u003csub\u003e2\u003c/sub\u003eO, ppm, 400MHz) δ ppm: 1.28 (t, 18H, 9CH\u003csub\u003e3\u003c/sub\u003e), 3.20 (q, 12H, 6CH\u003csub\u003e2\u003c/sub\u003e), 8.44 (s, 2H, H(3)), 9.59 (s, 2H, H(6)). \u003csup\u003e13\u003c/sup\u003eCNMR (295K, D\u003csub\u003e2\u003c/sub\u003eO, 125MHz) δ ppm: 8.04 (CH\u003csub\u003e3\u003c/sub\u003e), 46.64 (CH\u003csub\u003e2\u003c/sub\u003e), 120.33 (C(3)), 156.80 (C(6)), 160.48 (C(4)), 164.89 (C(2)), 168.80 (C(b)), 173.41 (C(a)), 193.00, 195.59 (CO). ESI-MS (m/z): [C\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e5\u003c/sub\u003eN\u003csub\u003e4\u003c/sub\u003eO\u003csub\u003e14\u003c/sub\u003eRe\u003csub\u003e2\u003c/sub\u003e]\u003csup\u003e\u0026minus;\u003c/sup\u003e or [\u003cb\u003e4\u003c/b\u003e\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e\u0026minus;\u003c/sup\u003e, calculated: 872.89, found: 872.91; [C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e10\u003c/sub\u003eN\u003csub\u003e5\u003c/sub\u003eO\u003csub\u003e14\u003c/sub\u003eRe\u003csub\u003e2\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e or [\u003cb\u003e4\u003c/b\u003e\u0026thinsp;+\u0026thinsp;3H\u0026thinsp;+\u0026thinsp;MeCN]\u003csup\u003e+\u003c/sup\u003e, calculated: 915.93, found: 916.10. UPLC (retention time min.): 2.06.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6. Synthesis of [(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)(\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e)]\u003csup\u003e2\u0026minus;\u003c/sup\u003e (5)\u003c/h2\u003e \u003cp\u003e600 \u0026micro;l of [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e in water, 300\u0026micro;l of 0.1M aqueous solution of pyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) and [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr] (0.84 mg, 2\u0026micro;mol) were mixed in vial which was sealed and flushed with N\u003csub\u003e2\u003c/sub\u003e for 15 min. The mixture was heated at 80\u003csup\u003eo\u003c/sup\u003eC for 45-min. The solution was brought to r.t. and injection of the product in the HPLC equipped by gamma and UV detectors displayed complex \u003cb\u003e5\u003c/b\u003e with a radiochemical yield of 35% and it is parallelly formed with complex \u003cb\u003e1\u003c/b\u003e and \u003cb\u003e2\u003c/b\u003e. By repeating this reaction with exclusion of [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e, dimeric complex \u003cb\u003e4\u003c/b\u003e was also formed.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results and discussion","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Synthesis of [Re(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(Hpmdc)] (1), [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(Hpmdc)] (2) and [Re(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(etpmdc)] (3)\u003c/h2\u003e \u003cp\u003eMonomeric complex [Re(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(Hpmdc)] (\u003cb\u003e1\u003c/b\u003e) was formed by reacting the chelating ligand pyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) with [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr] in distilled water (Scheme \u003cspan refid=\"Sch1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The formation of \u003cb\u003e1\u003c/b\u003e was enhanced by the denticity of H\u003csub\u003e2\u003c/sub\u003epmdc ligand and its good solubility in polar solvents like water. Complexes \u003cb\u003e1\u003c/b\u003e is orange-yellow colored and it is soluble in polar solvents like water, ethanol and methanol and display low solubility in non-polar solvents. Technetium (99m) complex homologous of \u003cb\u003e1\u003c/b\u003e typically [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(Hpmdc)] \u003cb\u003e(2)\u003c/b\u003e was directly formed from the reaction of \u003cem\u003efac\u003c/em\u003e-[\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e with H\u003csub\u003e2\u003c/sub\u003epmdc in water at 80\u003csup\u003eo\u003c/sup\u003eC for 30 min (Scheme \u003cspan refid=\"Sch1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Complex \u003cb\u003e2\u003c/b\u003e was also formed by heating aqueous \u003cem\u003efac\u003c/em\u003e-[\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e solution with H\u003csub\u003e2\u003c/sub\u003epmdc in microwave under the same reaction conditions. The Hpmdc\u003csup\u003e\u0026minus;\u003c/sup\u003e anion in the complexes \u003cb\u003e1\u003c/b\u003e and \u003cb\u003e2\u003c/b\u003e, coordinated to the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e core as bidentate N,O-donor chelate, coordinating to the metal center \u003cem\u003evia\u003c/em\u003e one of the pyrimidinic nitrogens and carboxylate-oxygen atoms, giving five-membered metallacycle ring (Scheme \u003cspan refid=\"Sch1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe complex [Re(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(etpmdc)] (\u003cb\u003e3\u003c/b\u003e) was obtained from the reaction of H\u003csub\u003e2\u003c/sub\u003epmdc with [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr] in ethanol. The formation of 6-(ethoxycarbonyl)pyrimidine-4-carboxylate (etpmdc\u003csup\u003e\u0026minus;\u003c/sup\u003e) anion was surprisingly enhanced by [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr]-catalysed mono-esterification of H\u003csub\u003e2\u003c/sub\u003epmdc and simultaneously coordinated to the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e core as Hpmdc\u003csup\u003e\u0026minus;\u003c/sup\u003e in \u003cb\u003e1\u003c/b\u003e and \u003cb\u003e2\u003c/b\u003e. The ability of rhenium(I) complexes [Re(CO)\u003csub\u003e5\u003c/sub\u003eX] (X\u0026thinsp;=\u0026thinsp;Cl, Br) to catalyse esterification reaction of carboxylic acid by alcohol was previously reported in the literature [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and it is supported by the Lewis acidity character of these complexes [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The reaction of 5-(5-aminopyrimidine-2,4(1H,3H)-dioxamido)-1,2,3,6-tetrahedro-2,6-dioxopyrimidine-4-carboxylic acid (H\u003csub\u003e2\u003c/sub\u003eamp) with [Re(CO)\u003csub\u003e5\u003c/sub\u003eCl] in ethanol which led to the rhenium(I) complex [Re(CO)\u003csub\u003e3\u003c/sub\u003e(H\u003csub\u003e2\u003c/sub\u003eO)(amef)] where amef is 5-(5-ammoniumpyrimidine-2,4(1H,3H)-dioxamido)-1,2,3,6-tetrahedro-2,6-dioxopyrimidine-4-ethylformate, and was formed by [Re(CO)\u003csub\u003e5\u003c/sub\u003eCl]-catalysed esterification of H\u003csub\u003e2\u003c/sub\u003eamp by ethanol, and coordinated to the fac-[Re(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e core as a bidentate N,N-donor chelate [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Complexes \u003cb\u003e3\u003c/b\u003e is orange and it is soluble in polar solvents like water, ethanol and methanol but not soluble in non-polar solvents. Attempt to synthesize \u003csup\u003e99m\u003c/sup\u003eTc complex homologous of \u003cb\u003e3\u003c/b\u003e in the same synthetic route as one used for the synthesis of [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(Hpmdc)] \u003cb\u003e(2)\u003c/b\u003e with addition of ethanol was not successful but the reaction also led to complex \u003cb\u003e2\u003c/b\u003e.\u003c/p\u003e\u003cp\u003eA variety of metal complexes of pyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) such as lanthanide(III) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], scandium (III) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and manganese(II) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] have been reported, and H\u003csub\u003e2\u003c/sub\u003epmdc ligand coordinated to the above-mentioned metal ions as in complexes \u003cb\u003e1\u003c/b\u003e and \u003cb\u003e2\u003c/b\u003e. To the best of our knowledge, the complexes [Re(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(Hpmdc)] (\u003cb\u003e1\u003c/b\u003e) and [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(Hpmdc)] \u003cb\u003e(2)\u003c/b\u003e are the first reported rhenium and technetium complexes with pyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) ligand. Due to the lability of aqua-ligand, complexes \u003cb\u003e1\u003c/b\u003e, \u003cb\u003e2\u003c/b\u003e and \u003cb\u003e3\u003c/b\u003e are biologically important as aqua-ligand have been identified to exchange with a variety of biological molecules in biological system [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Such exchange shall not affect the rest part of complexes \u003cb\u003e1\u003c/b\u003e, \u003cb\u003e2\u003c/b\u003e and \u003cb\u003e3\u003c/b\u003e as result of high kinetic and thermodynamic stability of complexes based on the organometallic \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e (M\u0026thinsp;=\u0026thinsp;Re and Tc) unit, granting the potential application of these complexes as radiopharmaceutical probes.\u003c/p\u003e \u003cp\u003eBy eluting complex \u003cb\u003e1\u003c/b\u003e in the ultraperformance liquid chromatography (UPLC) system, it was detected at the retention time of 1.80 min (Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). The vibrational peaks at 2042, 1908 and 1932 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e in the infrared spectrum of 1 (Fig. S2) are ascribed to the \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e, and they are at 1873, 1883, 2015 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e in 3 (Fig. S6). The peaks at 3225 and 3110 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e in 1 are ascribed to the ѵ(O\u0026thinsp;\u0026minus;\u0026thinsp;H) for the free OH in the coordinated ligand and water respectively whereas the ѵ(O\u0026thinsp;\u0026minus;\u0026thinsp;H) for the OH of the coordinated water in 3 occur at 3364 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (Figure S6). The \u003csup\u003e1\u003c/sup\u003eHNMR spectrum of \u003cb\u003e1\u003c/b\u003e in D\u003csub\u003e2\u003c/sub\u003eO (Fig. S3) displayed two protons H(3) and H(6) at 8.56 and 9.66 ppm respectively. Homologous protons in \u003cb\u003e3\u003c/b\u003e occur at 8.61 and 9.64 ppm respectively in the \u003csup\u003e1\u003c/sup\u003eHNMR of \u003cb\u003e3\u003c/b\u003e measured in CD\u003csub\u003e3\u003c/sub\u003eOD (Fig. S7). The triplet and quartet signals at 1.45 ppm and at 4.52 ppm in the \u003csup\u003e1\u003c/sup\u003eHNMR of \u003cb\u003e3\u003c/b\u003e are assigned to the -CH\u003csub\u003e3\u003c/sub\u003e and -CH\u003csub\u003e2\u003c/sub\u003e respectively, while the protons of the coordinated water are displayed as singlet signal at 4.07 ppm. The \u003csup\u003e13\u003c/sup\u003eCNMR in CD\u003csub\u003e3\u003c/sub\u003eOD gave the promised signals at 122.76, 159.52, 162.97, 167.41, 171.40, 175.89 ppm for \u003cb\u003e1\u003c/b\u003e (Fig. S4); and 123.13, 160.72, 160.76, 162.34, 164.30, 173.79 for \u003cb\u003e3\u003c/b\u003e (Fig. S8). The signals at 194.96 and 198.01 ppm are due to CO ligands in \u003cb\u003e1\u003c/b\u003e and they are at 197.37, 197.05, 193.94 ppm in \u003cb\u003e3\u003c/b\u003e. The signals at 14.85 and 64.88 ppm in the \u003csup\u003e13\u003c/sup\u003eC NMR of \u003cb\u003e3\u003c/b\u003e are ascribed to -CH\u003csub\u003e3\u003c/sub\u003e and -CH\u003csub\u003e2\u003c/sub\u003e respectively. Liquid chromatography-mass spectrometry (ESI-MS) analysis of complex \u003cb\u003e1\u003c/b\u003e (Fig. S5) displayed m/z peaks at 457.03 ascribed to [C\u003csub\u003e9\u003c/sub\u003eH\u003csub\u003e6\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e8\u003c/sub\u003eRe]\u003csup\u003e+\u003c/sup\u003e or [\u003cb\u003e1\u003c/b\u003e\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e and 438.06 in accordance with [C\u003csub\u003e9\u003c/sub\u003eH\u003csub\u003e4\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e7\u003c/sub\u003eRe]\u003csup\u003e+\u003c/sup\u003e or [\u003cb\u003e1\u003c/b\u003e-H\u003csub\u003e2\u003c/sub\u003eO\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e as well as 479.99 reflecting [C\u003csub\u003e11\u003c/sub\u003eH\u003csub\u003e7\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e7\u003c/sub\u003eRe]\u003csup\u003e+\u003c/sup\u003e or [\u003cb\u003e1\u003c/b\u003e\u0026thinsp;+\u0026thinsp;MeCN\u0026thinsp;+\u0026thinsp;H-H\u003csub\u003e2\u003c/sub\u003eO]\u003csup\u003e+\u003c/sup\u003e. Similarly, ESI-MS spectrum of \u003cb\u003e3\u003c/b\u003e (Fig. S9) showed m/z peaks typically 467.21 for [C\u003csub\u003e11\u003c/sub\u003eH\u003csub\u003e8\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e7\u003c/sub\u003eRe]\u003csup\u003e+\u003c/sup\u003e or [\u003cb\u003e3\u003c/b\u003e-H\u003csub\u003e2\u003c/sub\u003eO\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e, and 508.15 for [C\u003csub\u003e13\u003c/sub\u003eH\u003csub\u003e11\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e7\u003c/sub\u003eRe]\u003csup\u003e+\u003c/sup\u003e or [\u003cb\u003e3\u003c/b\u003e\u0026thinsp;+\u0026thinsp;MeCN\u0026thinsp;+\u0026thinsp;H-H\u003csub\u003e2\u003c/sub\u003eO]\u003csup\u003e+\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows ORTEP drawing of complex \u003cb\u003e3\u003c/b\u003e and its crystal details and structure refinement data are described in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The CCDC 2260652 contains the supplementary crystallographic data for \u003cb\u003e3\u003c/b\u003e, and can be obtained free of charge from the Cambridge Crystallographic Data Centre \u003cem\u003evia\u003c/em\u003e \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003ca href=\"http://www.ccdc.cam.ac.uk/data_request/cif\" target=\"_blank\"\u003ewww.ccdc.cam.ac.uk/data_request/cif\u003c/a\u003e\u003c/span\u003e\u003cspan address=\"http://www.ccdc.cam.ac.uk/data_request/cif\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. As generally observed to rhenium(I) complexes based on the \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e unit, the geometry around the rhenium metal center is a distorted octahedral [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], with oxygen atom of the coordinated water O(4) and two donor atoms N(1) and O(5) of etpmdc\u003csup\u003e\u0026minus;\u003c/sup\u003e anion in a facial arrangement as imposed by the \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e core.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStructure refinement parameters data and selected bond lengths (\u0026Aring;) and angles (˚) for [Re(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(etpmdc)] (\u003cb\u003e3\u003c/b\u003e)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStructure refinement Parameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStructure refinement Parameters data\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSelected bond lengths (\u0026Aring;) and angles (˚)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemical formula\u003c/p\u003e \u003cp\u003eFormula weight\u003c/p\u003e \u003cp\u003eTemperature (K)\u003c/p\u003e \u003cp\u003eCrystal system\u003c/p\u003e \u003cp\u003eSpace group\u003c/p\u003e \u003cp\u003eUnit cell dimensions (\u0026Aring;˚)\u003c/p\u003e \u003cp\u003eCrystal size/mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eVolume\u003c/em\u003e (\u0026Aring; \u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e\u003c/p\u003e \u003cp\u003eDensity (calc.) (g/cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003cp\u003eAbsorption coefficient (mm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e)\u003c/p\u003e \u003cp\u003e\u003cem\u003eF\u003c/em\u003e (000)\u003c/p\u003e \u003cp\u003e\u003cem\u003eRadiation\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eθ\u003c/em\u003e range for data collection (deg)\u003c/p\u003e \u003cp\u003eIndex ranges h,k,l max\u003c/p\u003e \u003cp\u003eReflections collected Independent reflections\u003c/p\u003e \u003cp\u003eData/restraints/parameters\u003c/p\u003e \u003cp\u003eGoodness-of-fit on \u003cem\u003eF\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eFinal R indexes [I\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;2σ (I)]\u003c/p\u003e \u003cp\u003eFinal R indexes [all data]\u003c/p\u003e \u003cp\u003eLargest diff. peak and hole(e/\u0026Aring;\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC\u003csub\u003e11\u003c/sub\u003eH\u003csub\u003e9\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e8\u003c/sub\u003eRe\u003c/p\u003e \u003cp\u003e483.40\u003c/p\u003e \u003cp\u003e160 K\u003c/p\u003e \u003cp\u003eMonoclinic\u003c/p\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e 2\u003csub\u003e1\u003c/sub\u003e\u003cem\u003e/c\u003c/em\u003e\u003c/p\u003e \u003cp\u003ea\u0026thinsp;=\u0026thinsp;7.05850(12) \u003cem\u003eα\u003c/em\u003e\u0026thinsp;=\u0026thinsp;90\u003c/p\u003e \u003cp\u003eb\u0026thinsp;=\u0026thinsp;7.82584(13) \u003cem\u003eβ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;93.1000(16)\u003c/p\u003e \u003cp\u003ec\u0026thinsp;=\u0026thinsp;24.5852(5) \u003cem\u003eγ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;90\u003c/p\u003e \u003cp\u003e0.14 \u0026times; 0.08 \u0026times; 0.01\u003c/p\u003e \u003cp\u003e1356.07(4)\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e2.368\u003c/p\u003e \u003cp\u003e9.006\u003c/p\u003e \u003cp\u003e912.0\u003c/p\u003e \u003cp\u003eMoKα (λ\u0026thinsp;=\u0026thinsp;0.71073)\u003c/p\u003e \u003cp\u003e5.464 to 61.016\u003c/p\u003e \u003cp\u003e-10\u0026thinsp;\u0026le;\u0026thinsp;h\u0026thinsp;\u0026le;\u0026thinsp;10,-10\u0026thinsp;\u0026le;\u0026thinsp;k\u0026thinsp;\u0026le;\u0026thinsp;11,-35\u0026thinsp;\u0026le;\u0026thinsp;l\u0026thinsp;\u0026le;\u0026thinsp;35\u003c/p\u003e \u003cp\u003e41731\u003c/p\u003e \u003cp\u003e4123 [R\u003csub\u003eint\u003c/sub\u003e =0.0320, R\u003csub\u003esigma\u003c/sub\u003e = 0.0157]\u003c/p\u003e \u003cp\u003e4123/0/208\u003c/p\u003e \u003cp\u003e1.148\u003c/p\u003e \u003cp\u003eR\u003csub\u003e1\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.0200, wR\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.0395\u003c/p\u003e \u003cp\u003eR\u003csub\u003e1\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.0227, wR\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.0402\u003c/p\u003e \u003cp\u003e1.53/-1.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRe(1)-C(1) 1.922(3)\u003c/p\u003e \u003cp\u003eRe(1)-C(2) 1.900(3)\u003c/p\u003e \u003cp\u003eRe(1)-C(3) 1.900(3)\u003c/p\u003e \u003cp\u003eRe(1)-O(4) 2.211(2)\u003c/p\u003e \u003cp\u003eRe(1)-O(5) 2.1489(19)\u003c/p\u003e \u003cp\u003eRe(1)-N(1) 2.179(2)\u003c/p\u003e \u003cp\u003eC(4)-O(5) 1.272(3)\u003c/p\u003e \u003cp\u003eC(4)-O(6) 1.235(3)\u003c/p\u003e \u003cp\u003eC(9)-O(7) 1.213(3)\u003c/p\u003e \u003cp\u003eC(9)-O(8) 1.309(3)\u003c/p\u003e \u003cp\u003eC(10)-O(8) 1.474(3)\u003c/p\u003e \u003cp\u003eC(5)-N(1) 1.349(3)\u003c/p\u003e \u003cp\u003eC(8)-N(1) 1.348(3)\u003c/p\u003e \u003cp\u003eC(8)-N(2) 1.327(3)\u003c/p\u003e \u003cp\u003eC(7)-N(2) 1.339(3)\u003c/p\u003e \u003cp\u003eC(2)-Re(1)-O(5) 175.09(11)\u003c/p\u003e \u003cp\u003eC(3)-Re(1)-O(4) 176.93(11)\u003c/p\u003e \u003cp\u003eC(1)-Re(1)-N(1) 170.68(11)\u003c/p\u003e \u003cp\u003eO(5)-Re(1)-N(1) 75.19(7)\u003c/p\u003e \u003cp\u003eRe(1)-C(1)-O(1) 176.9(3)\u003c/p\u003e \u003cp\u003eC(2)-Re(1)-C(1) 88.41(13)\u003c/p\u003e \u003cp\u003eO(5)-Re(1)-O(4) 83.39(7)\u003c/p\u003e \u003cp\u003eN(1)-Re(1)-O(4) 81.99(8)\u003c/p\u003e \u003cp\u003eC(3)-Re(1)-C(1) 86.41(14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe rhenium-centered bond angles C(2)-Re(1)-O(5)\u0026thinsp;=\u0026thinsp;175.09(11)\u003csup\u003eo\u003c/sup\u003e, C(3)-Re(1)-O(4)\u0026thinsp;=\u0026thinsp;176.93(6)\u003csup\u003eo\u003c/sup\u003e and C(1)-Re(1)-N(1)\u0026thinsp;=\u0026thinsp;170.68(11)\u003csup\u003eo\u003c/sup\u003e deviated from the linearity supporting the distortion in \u003cb\u003e3\u003c/b\u003e. Such distortion is furtherly supported by rhenium-centered bond angles C(2)-Re(1)-C(1)\u0026thinsp;=\u0026thinsp;88.41(13)\u003csup\u003eo\u003c/sup\u003e, (5)-Re(1)-O(4)\u0026thinsp;=\u0026thinsp;83.39(7) \u003csup\u003eo\u003c/sup\u003e, N(1)-Re(1)-O(4)\u0026thinsp;=\u0026thinsp;81.99(8)\u003csup\u003eo\u003c/sup\u003e and C(3)-Re(1)-C(1)\u0026thinsp;=\u0026thinsp;86.41(14) \u003csup\u003eo\u003c/sup\u003e which deviated from the orthogonality.\u003c/p\u003e \u003cp\u003eThe etpmdc\u003csup\u003e\u0026minus;\u003c/sup\u003e chelate coordinated to rhenium(I) center \u003cem\u003evia\u003c/em\u003e one of the pyrimidinic nitrogen N(1) and carboxylate oxygen O(5) forming a bite angle of O(5)-Re(1)-N(1)\u0026thinsp;=\u0026thinsp;75.19(7)\u003csup\u003eo\u003c/sup\u003e. For the reported similar pyrimidine derivatives complexes of rhenium(I), this angle was found 75.54(6)\u003csup\u003eo\u003c/sup\u003e and 75.14(5)\u003csup\u003e◦\u003c/sup\u003e [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. The bond distance Re(1)-O(5)\u0026thinsp;=\u0026thinsp;2.1489(19) \u0026Aring; in \u003cb\u003e3\u003c/b\u003e agrees well with the reported R\u003csup\u003eI\u003c/sup\u003e-O distances in pyrimidine derivatives complexes of rhenium(I) based on the \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e unit [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. The Re\u0026thinsp;\u0026minus;\u0026thinsp;N(1) bond distance of 2.179(2) \u0026Aring; is compatible with the range 2.15\u0026thinsp;\u0026minus;\u0026thinsp;2.22 \u0026Aring; previously reported for rhenium(I)\u0026thinsp;\u0026minus;\u0026thinsp;N(imines) distances [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. The average Re-C bond distances is 1.907(3) \u0026Aring;, and falls in the range 1.900(2)-1.928(2) \u0026Aring; reported for Re\u003csup\u003eI\u003c/sup\u003e-C distances [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The crystal packing diagram of \u003cb\u003e3\u003c/b\u003e (Fig. S16) displays two asymmetric units in the unit cell and four intramolecular hydrogen bonds (blue dashed) which are typically C(8)-H(8)..O(6), C(10)-H(10A)..O(3), O(4)-H(4A)..O(3) and O(4)-H(4B)..O(6).\u003c/p\u003e \u003cp\u003eDue to very low concentration of \u003csup\u003e99m\u003c/sup\u003eTc in solution which exists in nano-scale and similarity in the coordination chemistry of Re and Tc, the structural identity of \u003csup\u003e99m\u003c/sup\u003eTc-complexes is routinely confirmed by comparing their HPLC profiles with HPLC profiles of the homologous rhenium complexes, fully characterized by routine chemistry analytical techniques [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. This consists of coinjecting \u003csup\u003e99m\u003c/sup\u003eTc complex with its homologous rhenium complex in the HPLC with UV/vis detection coupled with a γ-detector followed by comparison of retention times of the displayed γ-peaks of \u003csup\u003e99m\u003c/sup\u003eTc complex and UV peak of Re complex [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Therefore, the chemical similarity of \u003cb\u003e1\u003c/b\u003e and \u003cb\u003e2\u003c/b\u003e was assessed by coinjection of 10 \u0026micro;l of these complexes in the HPLC with UV/vis detection coupled with a γ-detector, and complex \u003cb\u003e1\u003c/b\u003e was detected at R\u003csub\u003et\u003c/sub\u003e = 11.7 min in UV (Fig.\u0026nbsp;3b) which coincides with the radiochemical peak of \u003cb\u003e2\u003c/b\u003e detected at R\u003csub\u003et\u003c/sub\u003e = 12.8 min in γ (Fig.\u0026nbsp;3a) confirming their structural similarity. The difference of 1.1 min for \u003cb\u003e1\u003c/b\u003e and \u003cb\u003e2\u003c/b\u003e is due to the UV/vis and γ-detectors separation and HPLC settings [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Synthesis of (Et\u003csub\u003e3\u003c/sub\u003eNH)\u003csub\u003e2\u003c/sub\u003e[(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e (4) and [(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)(\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e)]\u003csup\u003e2\u0026minus;\u003c/sup\u003e (5)\u003c/h2\u003e \u003cp\u003eDimeric complex (Et\u003csub\u003e3\u003c/sub\u003eNH)\u003csub\u003e2\u003c/sub\u003e[(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e] (\u003cb\u003e4\u003c/b\u003e) was obtained from the reaction of H\u003csub\u003e2\u003c/sub\u003epmdc with [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr] in distilled water with addition of triethylamine (Et\u003csub\u003e3\u003c/sub\u003eN) as supporting base (Scheme \u003cspan refid=\"Sch2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Complexes \u003cb\u003e4\u003c/b\u003e is orange and it is soluble in polar solvents like water, ethanol and methanol, and exhibit a very low solubility in non-polar organic solvents. In the dimer \u003cb\u003e4\u003c/b\u003e, pmdc\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003e coordinated to the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e core as bidentate N,O-donor chelate, coordinating to the metal center \u003cem\u003evia\u003c/em\u003e on of the pyrimidinic nitrogen and carboxylate-oxygen atoms, and the other carboxylate oxygen atom is coordinated to the other \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e core. The reaction of [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e and [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr] with H\u003csub\u003e2\u003c/sub\u003epmdc led to the heterodinuclear \u003csup\u003e99m\u003c/sup\u003eTc/Re complex [(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)(\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e)]\u003csup\u003e2\u0026minus;\u003c/sup\u003e (\u003cb\u003e5\u003c/b\u003e) (Scheme \u003cspan refid=\"Sch2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), and it is parallelly formed with complexes \u003cb\u003e1\u003c/b\u003e and \u003cb\u003e2\u003c/b\u003e.\u003c/p\u003e\u003cp\u003eSimilar dimers of scandium(III) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] and manganese(II) [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] with H\u003csub\u003e2\u003c/sub\u003epmdc have been reported and pmdc\u003csup\u003e2\u0026minus;\u003c/sup\u003e coordinated to the metal center as in complexes \u003cb\u003e4\u003c/b\u003e and \u003cb\u003e5\u003c/b\u003e. Complex \u003cb\u003e4\u003c/b\u003e and \u003cb\u003e5\u003c/b\u003e have shown good stability in aqueous solution. The previous studies revealed that the pKa value of organic acid ligands reflects its relative coordination ability to the metal ions, and determine the strength of the resulting metal-ligand bonds, and therefore the stability of metal-organic framework [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. High value of pKa for organic acid ligands indicates its deprotonation weakness, and such ligand will mostly necessitate the supporting base to promote its deprotonation for coordinating to the metal ions [\u003cspan additionalcitationids=\"CR40\" citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. The deprotonated organic acid ligand with high value of pKa strongly coordinates to the metal ions resulting in metal-organic framework with high stability [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. The H\u003csub\u003e2\u003c/sub\u003epmdc ligand is a weak acid with pKa value of 2.035, and therefore, its full deprotonation for forming dinuclear rhenium complex \u003cb\u003e4\u003c/b\u003e necessitated triethyl amine (Et\u003csub\u003e3\u003c/sub\u003eN) as supporting base, and this complex has shown a significant stability. Similarly for forming heterodinuclear \u003csup\u003e99m\u003c/sup\u003eTc/Re complex \u003cb\u003e5\u003c/b\u003e, the full deprotonation of H\u003csub\u003e2\u003c/sub\u003epmdc has been supported by unidentified anionic base which is in place as a counterion of the cationic precursor complex [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn the infrared spectrum of \u003cb\u003e4\u003c/b\u003e (Fig. S11), sharp bands at 2016 and 1875 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e are associated with \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e units. In the \u003csup\u003e1\u003c/sup\u003eHNMR spectrum of \u003cb\u003e4\u003c/b\u003e in D\u003csub\u003e2\u003c/sub\u003eO (Fig. S12), the CH\u003csub\u003e3\u003c/sub\u003e and CH\u003csub\u003e2\u003c/sub\u003e protons of Et\u003csub\u003e3\u003c/sub\u003eNH\u003csup\u003e+\u003c/sup\u003e counterions occur as triplet at 1.28 ppm and quartet at 3.20 ppm respectively. The singlet signals at 8.44 and 9.59 ppm are ascribed to H(3) and H(6) respectively. The \u003csup\u003e13\u003c/sup\u003eCNMR of \u003cb\u003e4\u003c/b\u003e in D\u003csub\u003e2\u003c/sub\u003eO (Fig. S13) displayed signals at 8.04 and 46.64 ppm for CH\u003csub\u003e3\u003c/sub\u003e and CH\u003csub\u003e2\u003c/sub\u003e respectively for Et\u003csub\u003e3\u003c/sub\u003eNH\u003csup\u003e+\u003c/sup\u003e counterions. The carbon atoms of the coordinated pmdc\u003csup\u003e2\u0026minus;\u003c/sup\u003e ligands occur at 120.33, 156.80, 160.48, 164.89, 168.80 and 173.41 ppm; while the carbona toms of the CO ligands are displayed at 193.00 and 195.59 ppm. Complex \u003cb\u003e4\u003c/b\u003e was eluted in the UPLC and it was detected at 2.06 min (Fig. S10). The m/z peaks principally 872.91 [C\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e5\u003c/sub\u003eN\u003csub\u003e4\u003c/sub\u003eO\u003csub\u003e14\u003c/sub\u003eRe\u003csub\u003e2\u003c/sub\u003e]\u003csup\u003e\u0026minus;\u003c/sup\u003e or [\u003cb\u003e4\u003c/b\u003e\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e\u0026minus;\u003c/sup\u003e, 916.10 [C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e10\u003c/sub\u003eN\u003csub\u003e5\u003c/sub\u003eO\u003csub\u003e14\u003c/sub\u003eRe\u003csub\u003e2\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e or [\u003cb\u003e4\u003c/b\u003e\u0026thinsp;+\u0026thinsp;3H\u0026thinsp;+\u0026thinsp;MeCN]\u003csup\u003e+\u003c/sup\u003e were detected in liquid chromatography-mass spectrometry (ESI-MS) analysis of \u003cb\u003e4\u003c/b\u003e (Fig. S14 and Fig. S15) and furtherly confirmed its structure.\u003c/p\u003e \u003cp\u003eThe starting reagent used to synthesize compounds \u003cb\u003e1\u003c/b\u003e, \u003cb\u003e3\u003c/b\u003e and \u003cb\u003e4\u003c/b\u003e is [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr]. As the ligand H\u003csub\u003e2\u003c/sub\u003epmdc was deprotonated and release H\u003csup\u003e+\u003c/sup\u003e ions in solution, the bromide ions (Br\u003csup\u003e\u0026minus;\u003c/sup\u003e) reacted with H\u003csup\u003e+\u003c/sup\u003e ions from the deprotonated H\u003csub\u003e2\u003c/sub\u003epmdc to form hydrobromic acid (HBr) as reaction byproduct. The HBr is inorganic acid and due to its high solubility in organic solvents, it was eliminated by several time washing of compounds \u003cb\u003e1\u003c/b\u003e, \u003cb\u003e3\u003c/b\u003e and \u003cb\u003e4\u003c/b\u003e using organic solvents. In addition, the HBr has some degree of volatility and a particular quantity of it was eliminated by being volatilized in the air. Therefore, there is no Br maintained in the isolated materials of \u003cb\u003e1\u003c/b\u003e, \u003cb\u003e3\u003c/b\u003e and \u003cb\u003e4\u003c/b\u003e [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The formation of rhenium(I) complexes from [Re(CO)\u003csub\u003e5\u003c/sub\u003eX] (X\u0026thinsp;=\u0026thinsp;Cl, Br) without the ligand deprotonation only leads to rhenium(I) complexes with Br\u003csup\u003e\u0026minus;\u003c/sup\u003e or Cl\u003csup\u003e\u0026minus;\u003c/sup\u003e ligand maintained in the isolated products [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eInjection of 10 \u0026micro;l of the product from the reaction of [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e with H\u003csub\u003e2\u003c/sub\u003epmdc and [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr] in the HPLC with UV/vis detection coupled with a γ-detector displayed signals at retention times of 12.1 and 18.7 min in gamma with signal corresponding to the unreacted [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e and low intensity signal due to [\u003csup\u003e99m\u003c/sup\u003eTcO\u003csub\u003e4\u003c/sub\u003e]\u003csup\u003e\u0026minus;\u003c/sup\u003e from the oxidation of \u003csup\u003e99m\u003c/sup\u003eTc\u003csup\u003eI\u003c/sup\u003e to \u003csup\u003e99m\u003c/sup\u003eTc\u003csup\u003eVII\u003c/sup\u003e (Fig.\u0026nbsp;4a). It has also shown two signals in UV at 11.2 and 18.4 min (Fig.\u0026nbsp;3b). The signal at R\u003csub\u003et\u003c/sub\u003e = 11.2 min in UV (Fig.\u0026nbsp;4b) is due to the formation of [Re(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(Hpmdc)] (\u003cb\u003e1\u003c/b\u003e) which coincides with the radiochemical signal at R\u003csub\u003et\u003c/sub\u003e = 12.1 min in γ (Fig.\u0026nbsp;3a) suggesting the formation of [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(Hpmdc)] (\u003cb\u003e2\u003c/b\u003e) as observed in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The difference of 0.9 min for \u003cb\u003e1\u003c/b\u003e and \u003cb\u003e2\u003c/b\u003e is due to the detector separation and HPLC settings. The signal at R\u003csub\u003et\u003c/sub\u003e = 18.4 min in UV (Fig.\u0026nbsp;4b) is due to the formation of heterodinuclear \u003csup\u003e99m\u003c/sup\u003eTc/Re complex [(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)(\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e)]\u003csup\u003e2\u0026minus;\u003c/sup\u003e (\u003cb\u003e5\u003c/b\u003e) which coincides with its radiochemical signal at R\u003csub\u003et\u003c/sub\u003e = 18.7 min in γ (Fig.\u0026nbsp;4a), and the difference of 0.3 min is also due to the UV and γ-detectors separation and HPLC settings, and it was formed at yield of approximatively 35%. The obtained low yield of complex \u003cb\u003e5\u003c/b\u003e (35%) is due to the fact that it was parallelly formed with complex \u003cb\u003e1\u003c/b\u003e and \u003cb\u003e2\u003c/b\u003e. In addition, unreacted quantity of [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e and its small quantity which has been oxidized to [\u003csup\u003e99m\u003c/sup\u003eTcO\u003csub\u003e4\u003c/sub\u003e]\u003csup\u003e\u0026minus;\u003c/sup\u003e also partially contributed to such low yield of complex \u003cb\u003e5.\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe product at R\u003csub\u003et\u003c/sub\u003e = 18.7 min in γ is [(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)(\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e)]\u003csup\u003e2\u0026minus;\u003c/sup\u003e (\u003cb\u003e5\u003c/b\u003e) rather than the dimer [(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e]\u003csup\u003e2\u0026minus;\u003c/sup\u003e due to the fact that the low concentrations of \u003csup\u003e99m\u003c/sup\u003eTc makes the formation of dimeric \u003csup\u003e99m\u003c/sup\u003eTc species kinetically unlikely [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and even if it is formed, it should not be detected in the UV as observed for [(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)(\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e)]\u003csup\u003e2\u0026minus;\u003c/sup\u003e (\u003cb\u003e5\u003c/b\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e5\u003c/span\u003eb) due to its extremely low concentration. The formation of [(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)(\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e)]\u003csup\u003e2\u0026minus;\u003c/sup\u003e (\u003cb\u003e5\u003c/b\u003e) was furtherly confirmed by injecting its homologous non-radioactive dimer complex [(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e]\u003csup\u003e2\u0026minus;\u003c/sup\u003e (\u003cb\u003e4\u003c/b\u003e) in the same HPLC which also displayed the UV signal at 18.4 min equivalent to that of [(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)(\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e)]\u003csup\u003e2\u0026minus;\u003c/sup\u003e (\u003cb\u003e5\u003c/b\u003e) (Fig.\u0026nbsp;4b). The observed similar retention times in UV for \u003cb\u003e4\u003c/b\u003e and \u003cb\u003e5\u003c/b\u003e confirms their structural identity. This is furtherly supported by the fact that the metals technetium and rhenium are located in the same position in the Periodic Table of elements, and have comparable atomic radii, and their homologous complexes should consequently display the same electronic properties and coordination parameters [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Further characterizations of heterometallic radiocomplex \u003cb\u003e5\u003c/b\u003e are not applicable due to the above-mentioned reason of its low concentration in solution.\u003c/p\u003e \u003cp\u003eA few numbers of heterodinuclear complexes containing Re and \u003csup\u003e99m\u003c/sup\u003eTc were previously reported in the literature. Recently, the highly stable complex [\u003csup\u003e99m\u003c/sup\u003eTcRe\u003csub\u003e3\u003c/sub\u003e (\u0026micro;\u003csub\u003e3\u003c/sub\u003e-OH)\u003csub\u003e4\u003c/sub\u003e(CO)\u003csub\u003e12\u003c/sub\u003e] has been reported, and it was obtained at 94% yield from the reaction of aqueous [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e with [Re\u003csub\u003e3\u003c/sub\u003e (\u0026micro;\u003csub\u003e2\u003c/sub\u003e-OH)\u003csub\u003e3\u003c/sub\u003e(\u0026micro;\u003csub\u003e3\u003c/sub\u003e-OH)(CO)\u003csub\u003e9\u003c/sub\u003e]\u003csup\u003e\u0026minus;\u003c/sup\u003e [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The formation of \u003csup\u003e99m\u003c/sup\u003eTcRe\u003csub\u003e3\u003c/sub\u003e (\u0026micro;\u003csub\u003e3\u003c/sub\u003e-OH)\u003csub\u003e4\u003c/sub\u003e(CO)\u003csub\u003e12\u003c/sub\u003e] was also achieved at 90% yield from the reaction of aqueous [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e with (NEt\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e[ReBr\u003csub\u003e3\u003c/sub\u003e(CO)\u003csub\u003e3\u003c/sub\u003e] [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The reaction of (E)-2-((m-tolylimino)methyl)phenol ligand with [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003eand (NEt\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e[ReBr\u003csub\u003e3\u003c/sub\u003e(CO)\u003csub\u003e3\u003c/sub\u003e] in acetonitrile has been also studied, and led to the heterodinuclear \u003csup\u003e99m\u003c/sup\u003eTc/Re complex with exception stability [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Heterodinuclear \u003csup\u003e99m\u003c/sup\u003eTc/Re complex namely [Re(CO)\u003csub\u003e3\u003c/sub\u003e(bipy){(4-PyrIDA)\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e}] where 4-PyrIDA is N-carboxylato-N-(pyridin-4-ylmethyl)glycinate has been reported as the first example of \u003csup\u003e99m\u003c/sup\u003eTc/Re-based heterometallic assembly which could act as a potential bimodal optical/SPECT probe [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Such complex displayed similar retention time in the HPLC with its homologous dinuclear Re complex [Re(CO)\u003csub\u003e3\u003c/sub\u003e(bipy){(4-PyrIDA)Re(CO)\u003csub\u003e3\u003c/sub\u003e}] fully characterized by routine analytical techniques [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e] confirming their structural identity as observed for complexes \u003cb\u003e4\u003c/b\u003e and \u003cb\u003e5\u003c/b\u003e reported in this study. Dinuclear Re and its homologous heterodinuclear \u003csup\u003e99m\u003c/sup\u003eTc/Re complexes based on the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e core typically [Re(CO)\u003csub\u003e3\u003c/sub\u003e(pyta-COOMe){(4-pyrIDA)Re(CO)\u003csub\u003e3\u003c/sub\u003e}] and [Re(CO)\u003csub\u003e3\u003c/sub\u003e(pyta-COOMe){(4-pyrIDA)\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e}] where pyta-COOMe and PyrIDA are methyl 2-(4-(2-pyridyl)-[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]triazol-1-yl)acetate and 2,2'-((pyridin-4-ylmethyl)azanediyl)diacetate) respectively have been also reported [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Heterodinuclear \u003csup\u003e99m\u003c/sup\u003eTc/Re complex [Re(CO)\u003csub\u003e3\u003c/sub\u003e(pyta-COOMe){(4-pyrIDA)\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e}] was the first reported example of a functionalized dual fluorescent/radiolabeled imaging agent, and it was characterized by comparing its HPLC profile with the HPLC profile of its homologous and fully characterized dinuclear Re complex Re(CO)\u003csub\u003e3\u003c/sub\u003e(pyta-COOMe){(4-pyrIDA)Re(CO)\u003csub\u003e3\u003c/sub\u003e}] [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Both complexes displayed similar retention times in the HPLC as observed for complexes \u003cb\u003e4\u003c/b\u003e and \u003cb\u003e5\u003c/b\u003e reported in this study confirming their structural identity [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMultinuclear complexes are advantageous in medicinal inorganic chemistry as they may target more than one unit in the body, and can be delivered by more than one bioactive moiety [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In addition, the possibility of combining radiometal agents with cytotoxicity and imaging properties gave rise to a new concept of molecule-based theranostic radiopharmaceuticals with a specific amount of therapeutic and imaging agents [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In this way, the existence of similar coordination chemistry between Re and Tc makes possible to afford stable heterodinuclear \u003csup\u003e99m\u003c/sup\u003eTc/\u003csup\u003e186/188\u003c/sup\u003eRe complexes with \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e186/188\u003c/sup\u003eRe showing similar electronic properties, and such complexes act as theranostic radiopharmaceuticals displaying imaging and therapeutic properties [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Therefore, heterodinuclear \u003csup\u003e99m\u003c/sup\u003eTc/Re complex [(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)(\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e)]\u003csup\u003e2\u0026minus;\u003c/sup\u003e (\u003cb\u003e5\u003c/b\u003e) reported in this study will be a model for future design of theranostic radiopharmaceuticals combining imaging and therapy.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eIn this work, monomeric and dimeric complexes of the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e (M\u0026thinsp;=\u0026thinsp;Re and \u003csup\u003e99m\u003c/sup\u003eTc) core with pyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) ligand have been synthesized and characterized. These complexes are the model for future design of radiopharmaceuticals. The structural identification of \u003csup\u003e99m\u003c/sup\u003eTc-complexes is challenge due to its very low concertation in solution. As previously reported in the literature, the structural identity of \u003csup\u003e99m\u003c/sup\u003eTc-complexes reported in this study was achieved by comparing their HPLC profiles with HPLC profiles of their homologous rhenium complexes, fully characterized by routine chemistry analytical techniques. The existence of very low concentrations of \u003csup\u003e99m\u003c/sup\u003eTc in solution also make the color of its complexes not detectable, and they are always colorless, and it is the reason why the solution of complexes \u003cb\u003e2\u003c/b\u003e and \u003cb\u003e5\u003c/b\u003e did not show any color. Although the coordination mode of H\u003csub\u003e2\u003c/sub\u003epmdc in \u003cb\u003e1\u0026ndash;4\u003c/b\u003e was previously reported for other transition metal ions, compounds \u003cb\u003e1\u0026ndash;4\u003c/b\u003e are the first reported complexes of H\u003csub\u003e2\u003c/sub\u003epmdc with rhenium and technetium metals. In future, the reported heterodinuclear \u003csup\u003e99m\u003c/sup\u003eTc/Re complex \u003cb\u003e5\u003c/b\u003e will extend the theranostic modalities beyond mononuclear complexes. For further studies, our research efforts will be extended by reacting H\u003csub\u003e2\u003c/sub\u003epmdc with [\u003csup\u003e99\u003c/sup\u003eTcCl\u003csub\u003e3\u003c/sub\u003e(CO)\u003csub\u003e3\u003c/sub\u003e)]\u003csup\u003e2\u0026minus;\u003c/sup\u003e for ensuring that \u003csup\u003e99\u003c/sup\u003eTc complexes homologous to \u003cb\u003e1\u0026ndash;4\u003c/b\u003e will be formed. Furthermore, a mixture of [\u003csup\u003e99\u003c/sup\u003eTcCl\u003csub\u003e3\u003c/sub\u003e(CO)\u003csub\u003e3\u003c/sub\u003e)]\u003csup\u003e2\u0026minus;\u003c/sup\u003e with [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e and [ReBr(CO)\u003csub\u003e5\u003c/sub\u003e] with [\u003csup\u003e99\u003c/sup\u003eTcCl\u003csub\u003e3\u003c/sub\u003e(CO)\u003csub\u003e3\u003c/sub\u003e)]\u003csup\u003e2\u0026minus;\u003c/sup\u003e will be reacted with H\u003csub\u003e2\u003c/sub\u003epmdac ligand for ensuring that the heterodinuclear \u003csup\u003e99m\u003c/sup\u003eTc/\u003csup\u003e99\u003c/sup\u003eTc and \u003csup\u003e99\u003c/sup\u003eTc/Re complexes respectively similar to \u003cb\u003e5\u003c/b\u003e will be obtained. In addition, aqueous [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e and [ReBr(CO)\u003csub\u003e5\u003c/sub\u003e] will be reacted with the ligands analogous to H\u003csub\u003e2\u003c/sub\u003epmdc typically pyrimidine-4,6-diyldimethanol, hexahydropyrimidine-4,6-dicarboxylic acid and 1,2,3,4-tetrahydropyrimidine-4,6-dicarboxylic acid for ensuring that they will behave as H\u003csub\u003e2\u003c/sub\u003epmdc.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eDeclaration of Competing Interest\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJM: design the manuscript and synthesis and analysis of complexesGH: Writing Introduction and contribute crystal data interpretation and records.JS: Contributes in the interpretation of 1HNMR and HPLC data.TM: Contributes in Interpretation of IR and ESI-MS data and review of entire manuscript.JN: Contributes Literature reported in this manuscript as well as 13CNMR data interpretationTU: Contributes in writing the manuscript.TM: Edit the entire manuscript and provide input in interpretation of NMR and ESI-MS data.OB: He is the one who measured and provide data of the crystal structure reported in this manuscript.GB: Provide ideas in purification of the reported complexes and reviewed the entire manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eProf. Alberto Roger, Henrik Braband, University of Zurich and Research Group under Prof. Alberto Roger are strongly acknowledged.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eC.R. 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Steinbach, Strategic Evaluation of the Traceless Staudinger Ligation for Radiolabeling with the Tricarbonyl Core, \u003cem\u003eMolecules\u003c/em\u003e\u003cstrong\u003e26\u003c/strong\u003e, 6629 (2021), https://doi.org/10.3390/molecules26216629.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Schemes","content":"\u003cp\u003eSchemes 1 and 2 are available in the Supplementary Files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Monomeric complex, Dimeric complex, Pyrimidine-4,6-dicarboxylic acid, Rhenium, Technetium","lastPublishedDoi":"10.21203/rs.3.rs-4381286/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4381286/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe current study describes the synthesis of monomeric and dimeric complexes of pyrimidine-4,6-dicarboxylic acid (H\u003csub\u003e2\u003c/sub\u003epmdc) ligand with the organometallic \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e (M\u0026thinsp;=\u0026thinsp;Re and \u003csup\u003e99m\u003c/sup\u003eTc) core which are the model for future design of imaging, therapeutic and theranostic radiopharmaceuticals. Monomeric complexes [M(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(Hpmdc)] (M\u0026thinsp;=\u0026thinsp;Re (\u003cb\u003e1\u003c/b\u003e) and \u003csup\u003e99m\u003c/sup\u003eTc (\u003cb\u003e2\u003c/b\u003e)) were formed from the reaction of H\u003csub\u003e2\u003c/sub\u003epmdc with [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr] and [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e in aqueous solution respectively. The reaction of [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr] with H\u003csub\u003e2\u003c/sub\u003epmdc in ethanol (EtOH) led to the monomeric complex [Re(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)(etpmdc)] (\u003cb\u003e3\u003c/b\u003e), where etpmdc\u003csup\u003e\u0026minus;\u003c/sup\u003e is 6-(ethoxycarbonyl)pyrimidine-4-carboxylate anion which was formed from the mono-esterification of H\u003csub\u003e2\u003c/sub\u003epmdc in parallel with its coordination to the \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e unit. Dimeric complex (Et\u003csub\u003e3\u003c/sub\u003eNH)\u003csub\u003e2\u003c/sub\u003e[(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e (\u003cb\u003e4\u003c/b\u003e) was obtained from the reaction of [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr] with H\u003csub\u003e2\u003c/sub\u003epmdc in water with addition of triethylamine (Et\u003csub\u003e3\u003c/sub\u003eN) as supporting base. The chemical identification of \u003cb\u003e1\u003c/b\u003e, \u003cb\u003e3\u003c/b\u003e an\u003cb\u003ed 4\u003c/b\u003e was achieved by using \u003csup\u003e1\u003c/sup\u003eHNMR, \u003csup\u003e13\u003c/sup\u003eCNMR, IR, ESI-MS and elemental analysis. Complex \u003cb\u003e3\u003c/b\u003e was furtherly identified by using single crystal X-ray crystallography. The structural similarities of \u003cb\u003e1\u003c/b\u003e and \u003cb\u003e2\u003c/b\u003e was assessed by coinjection in the HPLC with UV/Vis detection coupled with a γ-detector followed by comparison of retention times of the γ-peak of \u003cb\u003e2\u003c/b\u003e and the UV-peak of \u003cb\u003e1\u003c/b\u003e which allowed unambiguous identification of \u003cb\u003e2\u003c/b\u003e. Heterodinuclear \u003csup\u003e99m\u003c/sup\u003eTc/Re complex [(\u0026micro;-pmdc)\u003csub\u003e2\u003c/sub\u003e(Re(CO)\u003csub\u003e3\u003c/sub\u003e)(\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e)]\u003csup\u003e2\u0026minus;\u003c/sup\u003e (\u003cb\u003e5\u003c/b\u003e) was formed by reacting H\u003csub\u003e2\u003c/sub\u003epmdc with [\u003csup\u003e99m\u003c/sup\u003eTc(CO)\u003csub\u003e3\u003c/sub\u003e(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e and [Re(CO)\u003csub\u003e5\u003c/sub\u003eBr] in aqueous solution. In parallel, the reaction also yielded complexes \u003cb\u003e1\u003c/b\u003e and \u003cb\u003e2\u003c/b\u003e. The formation of \u003cb\u003e5\u003c/b\u003e was assessed by injection in the HPLC with UV/Vis detection coupled with a γ-detector which displayed the radiochemical peak with the corresponding UV peak equivalent to that of the homologous non-radioactive complex \u003cb\u003e4\u003c/b\u003e.\u003c/p\u003e","manuscriptTitle":"Monomeric and dimeric complexes of pyrimidine-4,6-dicarboxylic acid with organometallic fac-[M(CO)3]+ (M = Re and 99mTc) core as radiopharmaceutical probes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-15 22:42:23","doi":"10.21203/rs.3.rs-4381286/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e6b7de46-b81b-4d41-a37f-6ff72cd83361","owner":[],"postedDate":"May 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-01T12:40:25+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-15 22:42:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4381286","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4381286","identity":"rs-4381286","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}