Organometallic complex of fac-[Re(CO) 3 ] + moiety with a modified tetraamine macroheterocyclic molecule dodecahydropyrimido[2',1':3,4]pyrazino[1,2-a]pyrimidine chelate: Synthesis and X-ray crystallography characterization

Organometallic complex of fac-[Re(CO) 3 ] + moiety with a modified tetraamine macroheterocyclic molecule dodecahydropyrimido[2',1':3,4]pyrazino[1,2-a]pyrimidine chelate: Synthesis and X-ray crystallography characterization | 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 Organometallic complex of fac-[Re(CO) 3 ] + moiety with a modified tetraamine macroheterocyclic molecule dodecahydropyrimido[2',1':3,4]pyrazino[1,2-a]pyrimidine chelate: Synthesis and X-ray crystallography characterization Gratien Habarurema, Eric Hosten, Janvier Mukiza, Richard Betz, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7489965/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Mar, 2026 Read the published version in Journal of Chemical Crystallography → Version 1 posted 4 You are reading this latest preprint version Abstract The demand for the design of novel anticancer drugs for chemotherapy and radiotherapy purposes is pressing due to cancer spreading worldwide, which is affecting a great number of people across the world. Among other existing compounds in the cancer chemotherapy, rhenium and technetium complexes are particularly emerging in the pipeline, and they are being investigated because of their promising biological applications and minimal in vivo toxicity. The coordination behaviour of various macromolecules around the fac -[Re(CO) 3 ] + moiety has significantly contributed to the preparation of various radiopharmaceuticals and other compounds with a variety of specific applications. Herein, we report the synthesis and characterization of an unusual non-radioactive rhenium complex fac -[Re(CO) 3 (H 2 dpp)Cl] ( 1 ) that was isolated from the reaction of Re(CO) 5 Cl with a crown macrocyclic tetraamine compound, (8 E ,10 E )-1,4,8,11-tetraazacyclotetradeca-8,10-diene (H 2 tazd) in toluene. This compound fac -[Re(CO) 3 (H 2 dpp)Cl] ( 1 ) was then crystallographically analysed using single X-ray diffraction techniques. The produced compound is a monomeric rhenium complex with H 2 dpp coordinating neutrally as a bidentate N , N′ -donor chelate. The unusual behavior observed in the crystal structure of ( 1 ) is dominated by the ring rearrangement of the used H 2 tazd ligand into the coordinated macromolecule chelate; dodecahydropyrimido[2',1':3,4]pyrazino[1,2-a]pyrimidine (H 2 dpp) molecule. The coordinated amine ligand, H 2 dpp is also a result of the intramolecular conversion process via the reduction of imine bonds in H 2 tazd, leadingd to a chelate with three fused rings in the structure of compound 1 . These findings revealed that both H 2 tazd and H 2 dpp macromolecules could be a source of macrocyclic chelating agents suitable for the preparation of a wide range of rhenium(I)-based complexes with the fac -[Re(CO) 3 ] + moiety. The refinement of compound 1 predicts the ring formation in the macrocyclic ligand, and this phenomenon is rare in the coordination chemistry of rhenium and was probably catalysed by rhenium(I) in the complex. Macromolecule rhenium(I) bidentate pharmaceutical X-Ray crystallography Figures Figure 1 Figure 2 1. Introduction The emergence of pharmaceuticals development for therapeutic and diagnosis application has become a great concern for researchers, as the commonly available drugs are increasingly becoming ineffective for the treatment of tumours and other related diseases [ 1 , 2 , 3 ]. In medicine,the diagnostic procedure of various affected tissues and organs (liver, kidney, heart) has been generally performed under the use of a number of medical imaging methods (fluorescent and ultrasound machines) [ 4 , 5 ] in conjunction with molecular techniques (Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT)) [ 6 , 7 ]. In addition, the latter molecular techniques are used while being coupled with some contrast agents of the metal complexes or radiotracers to investigate the interactions between the used pharmaceutical product and the target tissues such as vascular organs [ 7 ]. Alternatively, a major strategy consisting of developing new radiopharmaceuticals for anticancer therapy and diagnosis compounds involving the combination of an organic ligand with metal ions has been established [ 6 , 7 , 8 , 9 ]. Various transition metal complexes with macromolecule ligands such as those that bind to the DNA biomacromolecule have been extensively explored [ 8 , 9 , 10 ], and both rhenium and technetium have shown a great potential for coordinating to large biological active molecules, sometimes with pendant functional groups that can enhance the activity of the resulting complexes [ 10 , 11 , 12 ]. Studies have revealed that among different macromolecule chelates, lipids can be functionalized with rhenium complexes, creating molecules with interesting properties for biological studies [ 13 , 14 , 15 ]. These complexes were investigated for their unique biological applications and various physicochemical properties that can be be extended in materials science, biomedicine and industrial catalysis [ 16 ]. Moreover, the reactivity of group 7 transition metals including technetium and rhenium exhibits various oxidation states ranging from − 1 to + 7, thereby leading to various geometries depending on the ligand systems. This variability in oxidation states in various coordinating ligands was also reported to enhance their biological activities [ 17 , 18 ]. Macromolecular rhenium complexes may also incorporate their centers in potential synergistic effects in catalysis and/or other applications [ 18 , 19 ]. In addition, the compounds of its radioisotopes, 186/188 Re, as well as those of 99m Tc radionuclides with macromolecule chelates, are a prominent result in the development of radiopharmaceuticals for the bioimaging of cancer and antitumour therapy and diagnosis, respectively [ 20 – 23 ]. The oxidation state of the metal center and the system of the chelating group for complexation must be optmized to enhance the imaging and radiotherapy activities of both 99m Tc and 186/188 Re-based radiopharmaceuticals [ 24 , 25 ]. Consequently, technetium ( 99m Tc) [ 26 ], analogues of 186/188 Re can be synthesized for several specific applications [ 27 ], and the literature highlights several rhenium and technetium complexes in various oxidation states with specific pharmacokinetic applications were developed [ 26 , 27 , 28 ]. The examples of rhenium complex as intermediates for liposome labelling, such as 186 Re-BMEDA and 186 Re-BMEDA + BT were developed (benzene thiol (BT) and N , N -bis(2-mercaptoethyl)- N ', N '-diethylethylenediamine (BMEDA) [ 29 , 30 ]. On the other hand, 188-rhenium-diethylenetriaminepentaacetic acid ( 188 Re-DTPA) found its biological applications use in coronary angioplasty, and the compound was noticed to be a useful radiopharmaceutical for intravascular radiation therapy [ 29 , 31 ]. Some technetium-based radiopharmaceuticals were also reported in various studies [ 29 , 30 ]. A typical radiopharmaceutical example used in renography therapy consists of 99m Technetium-DTPA complex (DTPA = diethylene triamine penta-acetic acid (DTPA) chelate) commonly used to monitor renal function [ 29 ]. Interestingly, many other 99m Tc-based radiopharmaceuticals for clinical purposes in nuclear medicine, specifically as perfusion drugs for heart, were reported. This cardiolite complex; 99m Tc V -MIBI; methoxyisobutylisonitrile(MIBI)) [ 28 , 29 , 32 ], neurolite; 99m Tc V -ECD for brain, ceretec; 99m Tc V -meso-HMPAO and TechneScan MAG3; 99m Tc V -MAG3 were developed and have found specific applications as radiopharmaceuticals in diagnostic nuclear medicine [ 29 , 33 , 34 ]. It has been noted that various parameters of every pharmaceutical of rhenium or technetium, including the molecular size, oxidation state of the metal center, excellent stability, quick excretion, and adaptability, are of high importance in medicine [ 35 , 36 ]. Apart from the aforementioned rhenium and technetium complexes, the organometallic compounds of the fac -[M(CO) 3 ] + moiety (M = Re or Tc) with macromolecule chelating agents have also strongly attracted much attention in radiopharmaceutical chemistry, due to the interesting small size of their corresponding cores and high affinity towards a variety of ligands with various donor atoms [ 14 , 37 , 38 ]. Moreover, organometallic compounds with carbonyl groups of technetium and rhenium showed significant biological applications in nuclear medicine as previously reported [ 38 , 39 ]. These molecules provide extra benefits such as a unique mechanism of action, interaction with multiple targets, generation of reactive oxygen species, the inhibition of various pathogens, and lower toxicity [ 37 , 39 ]. Various investigations have proved that challenging cases may interfere while exploring the pharmacokinetics studies with only organic compounds without incorporating the distinctive characteristics of organometallic complexes (M = Re/Tc) [ 40 , 41 ]. In addition, these complexes might exhibit improved pharmacokinetics or lead to the development of new radiopharmaceuticals, owing to the unique radiochemical properties of the carbonyl core [ 40 , 41 , 42 ]. Various researchers have reported the main benefit of using the fac -[M(CO) 3 ] + (M = Re, TC) precursor during the synthesis of biomolecules, and their findings pointed out that a small quantity of the ligand is good enough to isolate the product, which displays a high and specific biological activity [ 43 – 46 ]. Various ligands have been studied to discover the most effective chelating systems for the carbonyl precursor for the synthesis of radiopharmaceuticals, and studies have demonstrated that macromolecules, including heterocyclic ligands with amine functional groups and sometimes with a carboxylic acid functional group, may form biomolecule complexes. The latter function groups with donor atoms show the ability to produce organometallic compounds with enhanced pharmacokinetics [46,47]. Various examples of Re-/Tc-carbonyl complexes with various macromolecule compounds have been previously reported, and among different investigated macrocyclic candidates, with a saturated tridentate amines and sulphur-containing compounds were explored [ 48 , 49 , 50 ]. All macrocyclic compounds, including 1,4,7-triazonane, 1,4,7-triazacyclononane and 1,5,9-triazacyclododecane (Scheme 1 ), displayed structural conditions suitable for acting as the tridentate chelates around the metal centers [ 50 ]. The present study reports the unusual synthesis route of a macrocycle ligand and its nonradioactive fac -[Re(CO) 3 ] +− based complex to predict the effectiveness of chelating ring structure on complexation behaviour. The title compound; fac -[Re(CO) 3 (H 2 dpp)Cl] was prepared from the reaction the reaction of Re(CO) 5 Cl and (8 E ,10 E )-1,4,8,11-tetraazacyclotetradeca-8,10-diene (H 2 tazd) under reflux in toluene. These results are in good agreement with the formation of fac -M(CO) 3 L where the derivative of H 2 tazd; dodecahydropyrimido[2',1':3,4]pyrazino[1,2-a]pyrimidine (H 2 dpp) is coordinated as a neutral bidentate chelate while only two among all four donor nitrogen atoms are coordinated. The crown ligand used during the reaction was dominated by an isomerization process leading to fused rings closure, and this might have been catalyzed by rhenium(I); fac -[Re(CO) 3 ] + moiety. 2.1 Experimental Details General Methods All the starting materials: Re(CO) 5 Cl, N 1 , N 1' -(ethane-1,2-diyl) bis (propane-1,3-diamine) and oxalaldehyde were obtained from Sigma-Aldrich, Japan Co.Ltd (Tokyo, Japan). The used chemicals and all solvents were of high grade and were used without any further purification after being dried following the reported procedure in the literature [ 51 ]. Various equipment were used for sample analysis. These include The Vario EL (Elementar Analysen system GmbH) instrument for elemental analysis of hydrogen, carbon and nitrogen. The crystals of the title compound, fac -[Re(CO) 3 (H 2 dpp)Cl] ( 1 ) was crystallographically analysed using single X-Ray diffraction techniques at 200 K using a Bruker Kappa Apex II diffractometer with graphite monochromated MoKa radiation (k = 0.71073Å). The data collection was carried out using APEX-II, whereas the cell refinement as well as data reduction was performed using SAINT [ 52 ]. The direct methods were used to solve the crystal structure by using SHELXS-2014 [ 53 ], and later, SHELXL-2014 was used to refine the crystal structure by least-squares procedures [ 50 ], and with SHELXLE as graphical interface [ 54 ]. The numerical methods or corrections implemented in SADABS was used for the correction of data for absorption effects [ 52 ]. The selected crystallographic data and all the detailed information and data of the crystal structure refinement are summarised in Table 1selected bond distances and bond angles are given in Table 2 . Various non-hydrogen atoms in the structure of compound 1 were anisotropically refined. All carbon-hydrogen bonds (C-H) atoms were placed in calculated positions, and their bond (C-H) distances were involved in the refinement in the riding model approximation, with Uiso(H) set to 1.2Ueq(C). All hydrogen atoms (H atoms) were allowed to undergo the rotation on a fixed angle along the C-C bond to correlate the experimental electron density map (HFIX 137 in SHELXL) [ 53 ], with Uiso(H) set to 1.5 Ueq(C). The PLATON graphical software was used to design both the molecular and crystal structure packing diagrams [ 55 ]. The CCDC 2237761 number containing the supplementary crystallographic data for fac -[Re(CO) 3 (H 2 dpp)Cl] ( 1 ), can be accessed free of charge from the Cambridge Crystallographic Data Centre via https://info.ccdc.cam.ac.uk/email-subscribe . 2. Synthesis of f-[Re(CO)(Hdpp)Cl] (1) To the solution of the organometallic precursor Re(CO) 5 Cl (150 mg, 131 µmol) in toluene (15 cm 3 ) was added solution of (8 E ,10 E )-1,4,8,11-tetraazacyclotetradeca-8,10-diene (H 2 tazd, 21.92 mg, 262 µmol) in 15 cm 3 of the same solvent. The resulting mixture was refluxed for 4 hours under a nitrogen atmosphere.. Thereafter, the reaction mixture was allowed to cool down to room temperature and then filtered to give an orange precipitate, which was dried under vacuum. After 2 weeks, quality orange crystals suitable for X-ray crystallography were grown upon slow evaporation of the mother liquor at room temperature. These crystals were washed using diethyl ether and then dried under vacuum To reach a yield of 77%, m.p. = 321°C. Anal. Calcd. (%) for C 18 H 6 N 2 O 10 Re 2 S 2 , 2(C 6 H 16 N) ( 1 ): C, 33.47; H, 4.32; N, 12.01; O, 10.27. Found: C, 31.02; H, 4.09; N, 11.7; O, 10.08. Conductivity (10 − 3 M, DMF): 12 Ω −1 cm 2 mol − 1 . 3. Results and Discussion 3.1 Preparation and characterization of fac -[Re(CO) 3 (H 2 dpp)Cl] (1 ) The complexation reaction was carried by reacting Re(CO) 5 Cl starting material and (8 E ,10 E )-1,4,8,11-tetraazacyclotetradeca-8,10-diene (H 2 tazd) in toluene solvent leading to a good yield (77%) of the product. The reaction was performed under higher temperature and a longer reaction time of 4 hours. The analysis indicated that a monomeric compound was produced. The isolated compound was purified and filtered and it was found to be stable in the air. However, this compound was soluble in many organic solvents such as dichloromethane (DCM), dimethyl sulfoxide (DMSO) and dimethylformamide (DMF). Very good quality orange crystals of ( 1 ), suitable for x-ray analysis were obtained two weeks following a slow evaporation of the mother liquor, thus contributing to an approximate good yield of 77% ( Scheme 1 and Figure 1 ). Interestingly, the crystal structure of compound 1 revealed that the coordinated H 2 dpp chelate acted as a bidentate neutral N , N -donor chelate . The proposed reaction scheme for the synthesis of fac -[Re(CO) 3 (H 2 dpp)Cl] (1 ) is dominated bythe inter-conversion of the used crown ligand (H 2 tazd) into the neutrally coordinated ligand, H 2 dpp characterized by the three fused rings and this ligand modification may be mediated by an intra-catalytic process by the coordinated rhenium(I) center. In addition, the mother ligand, H 2 tazd also underwent a reduction reaction upon ring formation thereby losing its two imine bonds. The synthesis route for compound 1 is shown by the reaction Scheme 1 : The ORTEP description of the molecular structure of compound 1 isshownin Figure 1 . Single crystals of compound 1 were crystallized as a monomeric molecule in the monoclinic system, space group I2/a., and the X-ray structure determination was crystallographically performed using x-ray diffraction method. The crystallographic data for the crystal structure of compound 1 as well as the refinement data are tabulated in Table 2. On the other hand, the selected important bond distances and bond angles of 1 shown in Table 3 , and a summary of all interactions are reported in Table 1 . A representation diagram of of the compound 1 , along with the atom numbering in its structure backbone is also presented in Figure 1 . The rhenium(I) metal center in the fac -[Re(CO) 3 ] + core lies in a distorted octahedral geometry with the three carbonyl groups distributed in a facial arrangement. The crystal structure of the molecule revealed that the coordination mode around rhenium(I) centers; Re(1) was accompanied by two Lewis base dissociation/association reactions described as a regular octahedron with a bidentate N , N ’-amine nitrogens, one chloride and three carbonyl groups in facial positions. The coordinated macrocyclic ligand displayed bidentate coordination fashion forming a five-metallacycle ring with rhenium metal center of the fac -[Re(CO) 3 ] + , resulting in the formation of a bite angle N(1)-Re(1)-N(1_a) with the average value of 77.61(6)°. This bite angle slightly deviates from the ideal angle of 90° for an octahedron in the metallacyclic part system. All the three Re-C bond lenghts, Re(1)-Cl(1) [1.887(6)Å ], Re(1)-C(2) [1.909(2)Å] and Re(1)-C(2_a) [1.909(2)Å] fall within the normal range expected for similar fac -tricarbonyl complexes [55,56], and these bonds are in line with the bond distances reported for many rhenium complexes [55,57]. Surprisingly, both Re-N bond lengths; Re(1)-N(1) and Re(1)-N(1_a) are equal with the bond distance of 2.2238(17) Å. The two bonds fall within the range reported for similar rhenium-nitrogen bond distances in comparison to other rhenium(I) complexes in the literature whereby nitrogen coordinates as a saturated donor atom [44,50,57,58]. The bond length; Re(1)-Cl(1) [2.4715(16)Å] confirms that the bond length between rhenium and chloride in similar reported complexes [60]. In addition, the distances and angles of the rhenium- amine and CO groups confirm that compound 1 is in a good agreement with the reported organometallic compounds, tricarbonyl-rhenium chloride of group 7 [60,61]. The three carbonyl ligands in a facial arrangement are a result of the formation of two equal non-linear trans bond angles N(1)-Re(1)-C(2) and N(1_a) -Re(1)-C(2_a) with a bond angle of 175.16(8)°, and a third nonlinear angle Cl(1)-Re(1)-C(1) [175.25(17)°] which is close to the first two angles. The overall observation shows that all these trans angle deviate from linearity. The coordinated H 2 dpp ligand had the possibility to coordinate as a N 4 -donor ligand. Surprisingly, it acted as a bidentate N 2 -donor chelate leaving behind two uncoordinated nitrogen atoms. The C-N bond lenghts N(1)-C(3) [1.482(2)Å], N(1)-C(6) [1.494(3)Å], N(2)-C(3) [1.449(2)Å], N(2)-C(4) [1.474(3)Å] and N(2)-C(7) [1.467(3)Å] are all single bonds which confirm that all nitrogen atoms in the coordinated H 2 dpp chelate are saturated, and bond around the rhenium(I) metal center as neutral atoms [44,57]. The C-N-C bond angles C(3)-N(1)-C(6), C(3)-N(2)-C(4), C(3)-N(2)-C(7) and C(4)-N(2)-C(7) of 109.50(15), 110.38(15), 109.01(17), 109.95(16), and 110.36(16) respectively are approximately equal, and also confirm that the corresponding bond distances in the fused rings of the H 2 dpp ligand are single bonds. Interestingly, the dihedral angle determined by the least square plane as described by ligand backbone between carbon and nitrogen atoms of the ring in 1 ;is C(4)-N(2)-C(7)-C(7_a) [180.00(18)°]. Additionally, the torsion angles observed, Cl(1)-Re(1)-N(1)-C(6) [57.74(14)°], C(1)-Re(1)-N(1)-C(3) [107.6(2)°] and C(2_a)-Re(1)-N(1)-C(3) [-163.13(12)°] contributed to the classical geometry of the molecule. In addition to the coordination behaviour of the ligand, the molecular system and dimensions around the metal center in compound ( 1 ) are of high interest in the coordination behaviour of rhenium(I) of the fac -[Re(CO) 3 )] + . In addition to all interactions in the molecule, the full spatial distribution of the ligands around the central rhenium(I) atom contributing to its facial isomer configuration is occasionally used to describe the solid state of the crystal structure of this compound. The molecular packing in the unit cell analysis showed significant insights dominated by the intra-molecular and non-covalent interactions displayed among the asymmetric units in the molecular crystal system. Following the hydrogen bond data analysis of the crystal structure of compound 1 , the observed substantial contributions to the stability of crystal structure in the packing of 1 are N1-H1•••Cl1 [3.170(2)Å] and N1-H1…O2 [3.201(2)Å] interactions. The data from the crystal refinement revealed that C-H•••O and N-H•••O and N-H•••Cl contacts also were involved in the stabilization of the geometry of the molecule as shown in the crystal packing (Table 1 and Figure 2). Table 1: Hydrogen-bonds and molecular interactions (Å,º) for fac -[Re(CO) 3 (H 2 dpp)Cl] ( 1 ) D − H … A D − H H … A D … A D − H … A N1-H1…Cl1 N1-H1…O2 C7-H7B...O1 0.82(2) 0.82(2) 0.9900 2.78(2) 2.49(2) 2.5200 3.170(2) 3.201(2) 3.441(5) 111.2(18) 145(2) 155.00 Table 2 : Crystallographic data and structure refinement data for fac -[Re(CO) 3 (H 2 dpp)Cl] (1 ) . Parameters Compound 1 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/m 3 ) Absorption coefficient (mm -1 ) F (000) Radiation θ range for data collection (deg) Index ranges h,k,l max Reflections Measured Reflections collected Independent reflections Data/parameters Goodness-of-fit on F 2 Final R indexes [I>=2σ (I)] Largest diff. peak and hole(e/Å 3 ) C 13 H 20 Cl N 4 O 3 Re 501.99 200 K Monoclinic I2/a a=11.7704(6) α = 90 b=10.8578(6) β =111.412(3) c=13.5622(5) γ = 90 0.13 x 0.18 x 0.25 1613.63(14) 4 2.066 7.713 968 MoKα (λ = 0.71073 ) 2.5 to 28.3 -15≤h≤15,-14≤ k14,-18≤ l≤18 1951 13705 2002 2002/118 1.23 R 1 =0.0112, wR 2 = 0.0247 0.44/-0.79 Table 3: Selected bond lengths ( Å ) and bond angles (°) for 1. Bond lengths Re(1)-Cl(1) Re(1)-N(1) Re(1)-C(1) Re(1)-C(2) Re(1)-Cl(1_a) Re(1)-N(1_a) Re(1)-C(1_a) Re(1)-C(2_a) C(5)-C(6) 2.4715(16) 2.2238(17) 1.887(6) 1.909(2) 2.4715(16) 2.2238(17) 1.887(6) 1.909(2) 1.516(3) N(1)-C(3) N(1)-C(6) N(2)-C(3) N(2)-C(4) N(2)-C(7) O(1)-C(1) O(2)-C(2) C(3)-C(3_a) C(4)-C(5) 1.482(2) 1.494(3) 1.449(2) 1.474(3) 1.467(3) 1.154(8) 1.157(3) 1.526(3) 1.514(3) Bond Angles Cl(1)-Re(1)-N(1) Cl(1)-Re(1)-C(1) Cl(1)-Re(1)-C(2) Cl(1)-Re(1)-Cl(1_a) Cl(1)-Re(1)-N(1_a) Cl(1)-Re(1)-C(2_a) N(1)-Re(1)-C(1) N(1)-Re(1)-C(2) N(1)-Re(1)-N(1_a) N(1)-Re(1)-C(1_a) N(1)-Re(1)-C(2_a) C(1)-Re(1)-C(2) N(1_a)-Re(1)-C(1) C(1)-Re(1)-C(1_a) C(1)-Re(1)-C(2_a) 86.33(6) 175.25(17) 94.03(7) 168.57(5) 84.76(6) 94.24(7) 90.00(18) 175.16(8) 77.61(6) 91.50(18) 97.61(8) 89.37(19) 91.50(18) 178.1(2) 89.23(19) N(1_a)-Re(1)-C(2) C(1_a)-Re(1)-C(2) C(2)-Re(1)-C(2_a) Cl(1_a)-Re(1)-N(1_a) Cl(1_a)-Re(1)-C(1_a) Cl(1_a)-Re(1)-C(2_a) N(1_a)-Re(1)-C(1_a) N(1_a)-Re(1)-C(2_a) C(1_a)-Re(1)-C(2_a) C(3)-N(1)-C(6) C(3)-N(2)-C(4) C(3)-N(2)-C(7) C(4)-N(2)-C(7) N(1)-C(3)-N(2) Cl(1_a)-Re(1)-C(2) 97.61(8) 89.23(19) 87.18(9) 86.33(6) 175.25(17) 94.03(7) 90.00(18) 175.16(8) 89.37(19) 109.50(15) 110.38(15) 109.01(17) 109.95(16) 110.36(16) 94.24(7) Conclusion The synthesis of bioorganometallic compounds brings a strong motivation for the investigation of the potential application of the simple fac -[Re(CO) 3 ] + moiety core in the pharmaceutical industry, biochemical applications and coordination chemistry of rhenium.. In this study, we have successfully synthesized, purified through crystalisation the novel Re-based tricarbonyl complex bearing a macromolecule-tetraamine chelate. The X-ray crystallography results of the obtained compound, fac -[Re(CO) 3 (H 2 dpp)Cl] (1) , showed that the metal fragment is coordinated to the ligand via N,N′-donor atoms. To the best of our knowledge, the reported complex herein is the first example of an organometallic compound whereby the used crown chelate underwent ligand modification leading to a coordinated chelate with fused rings. In addition, the imine bonds were reduced to saturated amine nitrogens, and this is a crucial observation in the coordination chemistry of rhenium(I). Our future research study will be extended to the investigation of various biological applications of the compound 1 , in addition to the characterization of the used ligand in this report as well as its coordination behaviour to other various rhenium and technetium cores. Declarations Declaration of competing interest The authors affirm that the work described in this paper has not been influenced by any competing interests. Funding The implementation of this research work was supported via the collaboration between the University of Rwanda-College of Science and Technology, other various colleges of University of Rwanda, Nelson Mandela University, Word academy of Science via the project; Research Grant Agreement (RGA) No. 20–145 RG/CHE/AF/AC_I – FR3240314142, as well as Uppsala University through the project research Grant application for 2019–2021, Research Groups and Scientific Networks under ISP, Uppsala University. Author Contribution According to the CRedit contribution taxonomy, G.H. performed the role of conceptualization, conducted laboratory work and wrote the main manuscript text. J.M. data curation, formal analysis and writing original draft. T.U played a role of validating the methodology prepared and reviewed all figures and schemes. TM. drafted and validated the experimental protocol. D.U. performed a role of conceptualization and reviewed the first draft. F.H. reviewed the systematic literature search. E.H and R.B. run the X-Ray crystallographic analysis of the compound. A.S.I. helped in data extraction. J.B.N. and J.B.H. helped in compilation of the manuscript, visualization, review and editing. T.G. supervised the research project, conceptualization, methodology, resources and writing-review and editing. In addition, all authors reviewed the Manuscript. Acknowledgments All forms of support from the Department of Chemistry of the University of Rwanda-College of Science and Technology, and the Government of Rwanda towards this research study are highly acknowledged. We are also grateful to the Chemistry Department of the Nelson Mandela University for providing laboratory equipment used for X-ray crystallographic data analysis. We express our gratitude to past and present co-workers and collaborators: Prof. Roger Alberto, Prof. Ignace Gatare, Mr. Vedaste Nyandwi, Prof. Théoneste Muhizi, Prof. Denis Ndanguza, Dr. Jean Bernard Ndayambaje, Prof. Zenixole Richman Tshentu, Dr. Adeniyi S. Ogunlaja for their contribution, motivation, enthusiasm and valuable experimental efforts provided during the implementation of this research study. Data Availability This article and all the supplementary materials containing all the information and data required to investigate the conclusions in the article are available and can be accessed *via* the CCDC 2237761. The dataset of our present research study is available in a structured database that is openly accessible. The Cambridge Crystallographic Data Centre has received crystallographic data for the chemical described here as Supporting Information. The dataset can be found at following link: https://info.ccdc.cam.ac.uk/email-subscribe. 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EJNMMI Res 10:79. https://doi.org/10.1186/s13550-020-00663-9 Murphy BL, Marker SC, Lambert VJ, Woods JJ, MacMillan SN, Wilson JJ (2020) Synthesis, characterization, and biological properties of rhenium (I) tricarbonyl complexes bearing nitrogen-donor ligands. J Organomet Chem 907:121064 Baumeister JE, Reinig KM, Barnes CL, Kelley SP, Jurisson SS (2018) Technetium and rhenium Schiff base compounds for nuclear medicine: syntheses of rhenium analogues to 99mTc-furifosmin. Inorg Chem 57(20):12920–12933 Binkley SL, Barone NV, Underwood AC, Milsted A, Franklin BR, Herrick RS, Ziegler CJ (2010) The synthesis and toxicity of tripodal tricarbonyl rhenium complexes as radiopharmaceutical models. J Inorg Biochem 104(6):632–638 Kianfar E, Monkowius U, Portenkirchner E, Knör G (2014) Synthesis and Characterization of Novel Re(BIAN)(CO) 3 Cl Derivatives Including the First Example of a Water-soluble Tricarbonyl Rhenium(I) Complex with Bis(imino)acenaphthene Ligands. Z für Naturforschung B 69(6):691–698. https://doi.org/10.5560/znb.2014-4016 Habarurema G, Mukiza J, Gerber TI, Mukabagorora T, Hosten EC, Betz R (2020) Imidazolidine ligands and their coordination behaviour towards the fac -[Re (CO) 3 ] + core: Unusual synthetic route, spectroscopic and X-Ray crystallographic characterization. J Organomet Chem 906:121033 Schemes Schemes 1 to 2 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files GraphicalAbstract.doc scheme1.jpg Scheme 1: Previously reported macromolecule line structures (a,b and c) [50], and (d,e,f and g) [44] used for the synthesis of organometallic complex of the fac -[M(CO) 3 ] + moiety (M= Re/Tc). scheme2.jpg Scheme 2: Synthetic route of complex f ac -[Re(CO) 3 (H 2 dpp)Cl] (1). Cite Share Download PDF Status: Published Journal Publication published 04 Mar, 2026 Read the published version in Journal of Chemical Crystallography → Version 1 posted Editorial decision: Revision requested 24 Sep, 2025 Editor assigned by journal 01 Sep, 2025 Submission checks completed at journal 01 Sep, 2025 First submitted to journal 29 Aug, 2025 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7489965","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":520161652,"identity":"890f0f37-731c-4620-8054-e8f21d2f1def","order_by":0,"name":"Gratien 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15:38:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7489965/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7489965/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10870-026-01085-6","type":"published","date":"2026-03-04T15:59:53+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":95719629,"identity":"9a91344e-387b-44b8-adff-dcb4aca5ca71","added_by":"auto","created_at":"2025-11-12 09:23:11","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":133139,"visible":true,"origin":"","legend":"\u003cp\u003eORTEP views of f\u003cem\u003eac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e(H\u003csub\u003e2\u003c/sub\u003edpp)Cl]\u003cstrong\u003e\u0026nbsp; (1)\u003c/strong\u003e showing the molecular geometry of the compound. Ellipsoids are drawn at 40% probability level. The labelling scheme used for the carbon atoms is omitted for clarity. The disordered groups in the crystal structure of \u003cstrong\u003e1\u003c/strong\u003e were truncated for clarity. Colour codes: Carbon = bluish, Hydrogen = white, Nitrogen = pulple, Chlorine = green and oxygen = red, rhenium = grey.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7489965/v1/a4f2fc9ca98b7278017fc516.jpg"},{"id":95719635,"identity":"f7770741-245f-4c27-98cc-dfb087624e60","added_by":"auto","created_at":"2025-11-12 09:23:12","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":160645,"visible":true,"origin":"","legend":"\u003cp\u003eParking diagram and perspective view in the unit cell of 1 displaying hydrogen-bond, molecular interactions and π-π stacking.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7489965/v1/917dd2676dfb13731b762576.jpg"},{"id":104251093,"identity":"3fd9035d-0adb-4fca-8f2b-129df0330607","added_by":"auto","created_at":"2026-03-09 16:11:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1182508,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7489965/v1/36baee6c-ec7e-42df-a763-045e0cd23a9d.pdf"},{"id":95719676,"identity":"76316014-9f72-4a97-95f3-841c5e54671d","added_by":"auto","created_at":"2025-11-12 09:23:17","extension":"doc","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":19456,"visible":true,"origin":"","legend":"","description":"","filename":"GraphicalAbstract.doc","url":"https://assets-eu.researchsquare.com/files/rs-7489965/v1/f87a83eb9080f9a29a627258.doc"},{"id":95719649,"identity":"6a3b89d6-7a93-43e2-a56e-4b771a6b1db2","added_by":"auto","created_at":"2025-11-12 09:23:13","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":83874,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 1\u003c/strong\u003e: Previously reported\u0026nbsp; macromolecule line structures (\u003cstrong\u003ea\u003c/strong\u003e,\u003cstrong\u003eb\u003c/strong\u003e and \u003cstrong\u003ec\u003c/strong\u003e) [50], and (\u003cstrong\u003ed\u003c/strong\u003e,\u003cstrong\u003ee\u003c/strong\u003e,\u003cstrong\u003ef\u003c/strong\u003e and \u003cstrong\u003eg\u003c/strong\u003e) [44] used for the synthesis of organometallic complex of the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e\u0026nbsp; moiety (M= Re/Tc).\u003c/p\u003e","description":"","filename":"scheme1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7489965/v1/eb3bbcc7fa1e1d759da05b45.jpg"},{"id":95719643,"identity":"91ce8d7e-3c2b-4ce3-b2ce-7490c8c517eb","added_by":"auto","created_at":"2025-11-12 09:23:12","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":60949,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 2\u003c/strong\u003e: Synthetic route of complex f\u003cem\u003eac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e(H\u003csub\u003e2\u003c/sub\u003edpp)Cl]\u003cstrong\u003e\u0026nbsp; (1)\u003c/strong\u003e.\u003c/p\u003e","description":"","filename":"scheme2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7489965/v1/4119c3e2ee5b73f1d31bbff1.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Organometallic complex of fac-[Re(CO) 3 ] + moiety with a modified tetraamine macroheterocyclic molecule dodecahydropyrimido[2',1':3,4]pyrazino[1,2-a]pyrimidine chelate: Synthesis and X-ray crystallography characterization","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe emergence of pharmaceuticals development for therapeutic and diagnosis application has become a great concern for researchers, as the commonly available drugs are increasingly becoming ineffective for the treatment of tumours and other related diseases [\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]. In medicine,the diagnostic procedure of various affected tissues and organs (liver, kidney, heart) has been generally performed under the use of a number of medical imaging methods (fluorescent and ultrasound machines) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] in conjunction with molecular techniques (Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT)) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In addition, the latter molecular techniques are used while being coupled with some contrast agents of the metal complexes or radiotracers to investigate the interactions between the used pharmaceutical product and the target tissues such as vascular organs [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Alternatively, a major strategy consisting of developing new radiopharmaceuticals for anticancer therapy and diagnosis compounds involving the combination of an organic ligand with metal ions has been established [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Various transition metal complexes with macromolecule ligands such as those that bind to the DNA biomacromolecule have been extensively explored [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], and both rhenium and technetium have shown a great potential for coordinating to large biological active molecules, sometimes with pendant functional groups that can enhance the activity of the resulting complexes [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Studies have revealed that among different macromolecule chelates, lipids can be functionalized with rhenium complexes, creating molecules with interesting properties for biological studies [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. These complexes were investigated for their unique biological applications and various physicochemical properties that can be be extended in materials science, biomedicine and industrial catalysis [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Moreover, the reactivity of group 7 transition metals including technetium and rhenium exhibits various oxidation states ranging from − 1 to + 7, thereby leading to various geometries depending on the ligand systems. This variability in oxidation states in various coordinating ligands was also reported to enhance their biological activities [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Macromolecular rhenium complexes may also incorporate their centers in potential synergistic effects in catalysis and/or other applications [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In addition, the compounds of its radioisotopes, \u003csup\u003e186/188\u003c/sup\u003eRe, as well as those of \u003csup\u003e99m\u003c/sup\u003eTc radionuclides with macromolecule chelates, are a prominent result in the development of radiopharmaceuticals for the bioimaging of cancer and antitumour therapy and diagnosis, respectively [\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e–\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The oxidation state of the metal center and the system of the chelating group for complexation must be optmized to enhance the imaging and radiotherapy activities of both \u003csup\u003e99m\u003c/sup\u003eTc and \u003csup\u003e186/188\u003c/sup\u003eRe-based radiopharmaceuticals [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Consequently, technetium (\u003csup\u003e99m\u003c/sup\u003eTc) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], analogues of \u003csup\u003e186/188\u003c/sup\u003eRe can be synthesized for several specific applications [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], and the literature highlights several rhenium and technetium complexes in various oxidation states with specific pharmacokinetic applications were developed [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The examples of rhenium complex as intermediates for liposome labelling, such as \u003csup\u003e186\u003c/sup\u003eRe-BMEDA and \u003csup\u003e186\u003c/sup\u003eRe-BMEDA + BT were developed (benzene thiol (BT) and \u003cem\u003eN\u003c/em\u003e, \u003cem\u003eN\u003c/em\u003e-bis(2-mercaptoethyl)-\u003cem\u003eN\u003c/em\u003e', \u003cem\u003eN\u003c/em\u003e'-diethylethylenediamine (BMEDA) [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOn the other hand, 188-rhenium-diethylenetriaminepentaacetic acid (\u003csup\u003e188\u003c/sup\u003eRe-DTPA) found its biological applications use in coronary angioplasty, and the compound was noticed to be a useful radiopharmaceutical for intravascular radiation therapy [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Some technetium-based radiopharmaceuticals were also reported in various studies [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. A typical radiopharmaceutical example used in renography therapy consists of \u003csup\u003e99m\u003c/sup\u003eTechnetium-DTPA complex (DTPA = diethylene triamine penta-acetic acid (DTPA) chelate) commonly used to monitor renal function [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Interestingly, many other \u003csup\u003e99m\u003c/sup\u003eTc-based radiopharmaceuticals for clinical purposes in nuclear medicine, specifically as perfusion drugs for heart, were reported. This cardiolite complex; \u003csup\u003e99m\u003c/sup\u003eTc\u003csup\u003eV\u003c/sup\u003e-MIBI; methoxyisobutylisonitrile(MIBI)) [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], neurolite; \u003csup\u003e99m\u003c/sup\u003eTc\u003csup\u003eV\u003c/sup\u003e-ECD for brain, ceretec; \u003csup\u003e99m\u003c/sup\u003eTc\u003csup\u003eV\u003c/sup\u003e-meso-HMPAO and TechneScan MAG3; \u003csup\u003e99m\u003c/sup\u003eTc\u003csup\u003eV\u003c/sup\u003e-MAG3 were developed and have found specific applications as radiopharmaceuticals in diagnostic nuclear medicine [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIt has been noted that various parameters of every pharmaceutical of rhenium or technetium, including the molecular size, oxidation state of the metal center, excellent stability, quick excretion, and adaptability, are of high importance in medicine [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Apart from the aforementioned rhenium and technetium complexes, the organometallic compounds of the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e moiety (M = Re or Tc) with macromolecule chelating agents have also strongly attracted much attention in radiopharmaceutical chemistry, due to the interesting small size of their corresponding cores and high affinity towards a variety of ligands with various donor atoms [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Moreover, organometallic compounds with carbonyl groups of technetium and rhenium showed significant biological applications in nuclear medicine as previously reported [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. These molecules provide extra benefits such as a unique mechanism of action, interaction with multiple targets, generation of reactive oxygen species, the inhibition of various pathogens, and lower toxicity [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Various investigations have proved that challenging cases may interfere while exploring the pharmacokinetics studies with only organic compounds without incorporating the distinctive characteristics of organometallic complexes (M = Re/Tc) [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. In addition, these complexes might exhibit improved pharmacokinetics or lead to the development of new radiopharmaceuticals, owing to the unique radiochemical properties of the carbonyl core [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eVarious researchers have reported the main benefit of using the \u003cem\u003efac\u003c/em\u003e-[M(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e (M = Re, TC) precursor during the synthesis of biomolecules, and their findings pointed out that a small quantity of the ligand is good enough to isolate the product, which displays a high and specific biological activity [\u003cspan additionalcitationids=\"CR44 CR45\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e–\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Various ligands have been studied to discover the most effective chelating systems for the carbonyl precursor for the synthesis of radiopharmaceuticals, and studies have demonstrated that macromolecules, including heterocyclic ligands with amine functional groups and sometimes with a carboxylic acid functional group, may form biomolecule complexes. The latter function groups with donor atoms show the ability to produce organometallic compounds with enhanced pharmacokinetics [46,47]. Various examples of Re-/Tc-carbonyl complexes with various macromolecule compounds have been previously reported, and among different investigated macrocyclic candidates, with a saturated tridentate amines and sulphur-containing compounds were explored [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e48\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. All macrocyclic compounds, including 1,4,7-triazonane, 1,4,7-triazacyclononane and 1,5,9-triazacyclododecane (Scheme \u003cspan refid=\"Sch1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), displayed structural conditions suitable for acting as the tridentate chelates around the metal centers [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e50\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe present study reports the unusual synthesis route of a macrocycle ligand and its nonradioactive \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+−\u003c/sup\u003ebased complex to predict the effectiveness of chelating ring structure on complexation behaviour. The title compound; \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e(H\u003csub\u003e2\u003c/sub\u003edpp)Cl] was prepared from the reaction the reaction of Re(CO)\u003csub\u003e5\u003c/sub\u003eCl and (8\u003cem\u003eE\u003c/em\u003e,10\u003cem\u003eE\u003c/em\u003e)-1,4,8,11-tetraazacyclotetradeca-8,10-diene (H\u003csub\u003e2\u003c/sub\u003etazd) under reflux in toluene. These results are in good agreement with the formation of \u003cem\u003efac\u003c/em\u003e-M(CO)\u003csub\u003e3\u003c/sub\u003eL where the derivative of H\u003csub\u003e2\u003c/sub\u003etazd; dodecahydropyrimido[2',1':3,4]pyrazino[1,2-a]pyrimidine (H\u003csub\u003e2\u003c/sub\u003edpp) is coordinated as a neutral bidentate chelate while only two among all four donor nitrogen atoms are coordinated. The crown ligand used during the reaction was dominated by an isomerization process leading to fused rings closure, and this might have been catalyzed by rhenium(I); \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e moiety.\u003c/p\u003e"},{"header":"2.1 Experimental Details","content":"\u003cp\u003e\u003cb\u003eGeneral Methods\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAll the starting materials: Re(CO)\u003csub\u003e5\u003c/sub\u003eCl, \u003cem\u003eN\u003c/em\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e,\u003cem\u003eN\u003c/em\u003e\u003csup\u003e\u003cem\u003e1'\u003c/em\u003e\u003c/sup\u003e-(ethane-1,2-diyl)\u003cem\u003ebis\u003c/em\u003e(propane-1,3-diamine) and oxalaldehyde were obtained from Sigma-Aldrich, Japan Co.Ltd (Tokyo, Japan). The used chemicals and all solvents were of high grade and were used without any further purification after being dried following the reported procedure in the literature [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. Various equipment were used for sample analysis. These include The Vario EL (Elementar Analysen system GmbH) instrument for elemental analysis of hydrogen, carbon and nitrogen. The crystals of the title compound, \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e(H\u003csub\u003e2\u003c/sub\u003edpp)Cl] (\u003cb\u003e1\u003c/b\u003e) was crystallographically analysed using single X-Ray diffraction techniques at 200 K using a Bruker Kappa Apex II diffractometer with graphite monochromated MoKa radiation (k = 0.71073Å). The data collection was carried out using APEX-II, whereas the cell refinement as well as data reduction was performed using SAINT [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. The direct methods were used to solve the crystal structure by using SHELXS-2014 [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e53\u003c/span\u003e], and later, SHELXL-2014 was used to refine the crystal structure by least-squares procedures [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e50\u003c/span\u003e], and with SHELXLE as graphical interface [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. The numerical methods or corrections implemented in SADABS was used for the correction of data for absorption effects [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. The selected crystallographic data and all the detailed information and data of the crystal structure refinement are summarised in Table\u0026nbsp;1selected bond distances and bond angles are given in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Various non-hydrogen atoms in the structure of compound \u003cb\u003e1\u003c/b\u003e were anisotropically refined. All carbon-hydrogen bonds (C-H) atoms were placed in calculated positions, and their bond (C-H) distances were involved in the refinement in the riding model approximation, with Uiso(H) set to 1.2Ueq(C). All hydrogen atoms (H atoms) were allowed to undergo the rotation on a fixed angle along the C-C bond to correlate the experimental electron density map (HFIX 137 in SHELXL) [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e53\u003c/span\u003e], with Uiso(H) set to 1.5 Ueq(C). The PLATON graphical software was used to design both the molecular and crystal structure packing diagrams [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. The CCDC 2237761 number containing the supplementary crystallographic data for \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e(H\u003csub\u003e2\u003c/sub\u003edpp)Cl] (\u003cb\u003e1\u003c/b\u003e), can be accessed free of charge from the Cambridge Crystallographic Data Centre \u003cem\u003evia\u003c/em\u003e \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://info.ccdc.cam.ac.uk/email-subscribe\u003c/span\u003e\u003cspan address=\"https://info.ccdc.cam.ac.uk/email-subscribe\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/p\u003e\u003ch3\u003e2. Synthesis of f-[Re(CO)(Hdpp)Cl] (1)\u003c/h3\u003e\u003cp\u003eTo the solution of the organometallic precursor Re(CO)\u003csub\u003e5\u003c/sub\u003eCl (150 mg, 131 µmol) in toluene (15 cm\u003csup\u003e3\u003c/sup\u003e) was added solution of (8\u003cem\u003eE\u003c/em\u003e,10\u003cem\u003eE\u003c/em\u003e)-1,4,8,11-tetraazacyclotetradeca-8,10-diene (H\u003csub\u003e2\u003c/sub\u003etazd, 21.92 mg, 262 µmol) in 15 cm\u003csup\u003e3\u003c/sup\u003e of the same solvent. The resulting mixture was refluxed for 4 hours under a nitrogen atmosphere.. Thereafter, the reaction mixture was allowed to cool down to room temperature and then filtered to give an orange precipitate, which was dried under vacuum. After 2 weeks, quality orange crystals suitable for X-ray crystallography were grown upon slow evaporation of the mother liquor at room temperature. These crystals were washed using diethyl ether and then dried under vacuum To reach a yield of 77%, m.p. = 321°C. Anal. Calcd. (%) for C\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e6\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e10\u003c/sub\u003eRe\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e, 2(C\u003csub\u003e6\u003c/sub\u003e H\u003csub\u003e16\u003c/sub\u003e N) (\u003cb\u003e1\u003c/b\u003e): C, 33.47; H, 4.32; N, 12.01; O, 10.27. Found: C, 31.02; H, 4.09; N, 11.7; O, 10.08. Conductivity (10\u003csup\u003e− 3\u003c/sup\u003e M, DMF): 12 Ω\u003csup\u003e−1\u003c/sup\u003ecm\u003csup\u003e2\u003c/sup\u003emol\u003csup\u003e− 1\u003c/sup\u003e.\u003c/p\u003e"},{"header":"3. Results and Discussion","content":"\u003cp\u003e\u003cstrong\u003e3.1 Preparation and characterization of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003efac\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e(H\u003csub\u003e2\u003c/sub\u003edpp)Cl] (1\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe complexation reaction was carried by reacting Re(CO)\u003csub\u003e5\u003c/sub\u003eCl starting material and\u0026nbsp;(8\u003cem\u003eE\u003c/em\u003e,10\u003cem\u003eE\u003c/em\u003e)-1,4,8,11-tetraazacyclotetradeca-8,10-diene\u0026nbsp;(H\u003csub\u003e2\u003c/sub\u003etazd) in toluene solvent leading to a\u0026nbsp;good yield (77%) of the product. The reaction was performed under higher temperature and a longer reaction time of 4 hours. The analysis indicated that a monomeric compound was produced. The isolated compound was purified and filtered and it was found to be stable in the air. However, this compound was soluble in many organic solvents such as dichloromethane (DCM), dimethyl sulfoxide (DMSO) and dimethylformamide (DMF). Very good quality orange crystals of (\u003cstrong\u003e1\u003c/strong\u003e), suitable for x-ray analysis were obtained two weeks following a slow evaporation of the mother liquor, thus contributing to an approximate good yield of 77% (\u003cstrong\u003eScheme 1\u003c/strong\u003e and \u003cstrong\u003eFigure 1\u003c/strong\u003e). Interestingly, the crystal structure of compound \u003cstrong\u003e1\u0026nbsp;\u003c/strong\u003erevealed that the coordinated H\u003csub\u003e2\u003c/sub\u003edpp chelate acted as a bidentate neutral \u0026nbsp;\u003cem\u003eN\u003c/em\u003e,\u003cem\u003eN\u003c/em\u003e-donor chelate . The proposed reaction scheme for the synthesis of \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e(H\u003csub\u003e2\u003c/sub\u003edpp)Cl]\u003cstrong\u003e\u0026nbsp; (1\u003c/strong\u003e\u003cstrong\u003e)\u0026nbsp;\u003c/strong\u003eis dominated bythe inter-conversion of the used crown ligand (H\u003csub\u003e2\u003c/sub\u003etazd) into the neutrally coordinated ligand, H\u003csub\u003e2\u003c/sub\u003edpp characterized by the three fused rings and this ligand modification may be mediated by an intra-catalytic process by the coordinated rhenium(I) center. In addition, the mother ligand, H\u003csub\u003e2\u003c/sub\u003etazd also underwent a reduction reaction upon ring formation thereby losing its two imine bonds. The synthesis route for compound \u003cstrong\u003e1\u003c/strong\u003e is shown by the reaction \u003cstrong\u003eScheme 1\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe ORTEP description of the molecular structure of compound \u003cstrong\u003e1\u0026nbsp;\u003c/strong\u003eisshownin \u003cstrong\u003eFigure 1\u003c/strong\u003e. Single crystals of compound \u003cstrong\u003e1\u003c/strong\u003e were crystallized as a monomeric molecule in the monoclinic system, space group I2/a., and the X-ray structure determination was crystallographically performed \u0026nbsp;using x-ray diffraction method. The crystallographic data for the crystal structure of compound \u003cstrong\u003e1\u003c/strong\u003e as well as the refinement data are tabulated in Table 2. On the other hand, the selected important bond distances and bond angles of \u003cstrong\u003e1\u003c/strong\u003e shown in \u003cstrong\u003eTable 3\u003c/strong\u003e, and a summary of all interactions are reported in \u003cstrong\u003eTable 1\u003c/strong\u003e. A representation diagram of \u0026nbsp;of the compound \u003cstrong\u003e1\u003c/strong\u003e, along with the atom numbering in its structure backbone \u0026nbsp;is also presented in \u003cstrong\u003eFigure 1\u003c/strong\u003e. The rhenium(I) metal center in the \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e core lies in a distorted octahedral geometry with the three carbonyl groups distributed in a facial arrangement. The crystal structure of the molecule revealed that the coordination mode around rhenium(I) centers; Re(1) was accompanied by two Lewis base dissociation/association reactions described as a regular octahedron with a bidentate \u003cem\u003eN\u003c/em\u003e,\u003cem\u003eN\u003c/em\u003e\u0026rsquo;-amine nitrogens, one chloride and three carbonyl groups in facial positions. The coordinated macrocyclic ligand displayed bidentate coordination fashion forming a five-metallacycle ring with rhenium metal center of the \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e, resulting in the formation of a bite angle N(1)-Re(1)-N(1_a) with the average value of 77.61(6)\u0026deg;. This bite angle slightly deviates from the ideal angle of 90\u0026deg; for an octahedron in the metallacyclic part system. All the three Re-C bond lenghts, Re(1)-Cl(1) [1.887(6)\u0026Aring; ], Re(1)-C(2) [1.909(2)\u0026Aring;] and Re(1)-C(2_a) [1.909(2)\u0026Aring;] fall within the normal range expected for similar \u003cem\u003efac\u003c/em\u003e-tricarbonyl complexes [55,56], and these bonds are in line with the bond distances reported for many rhenium complexes [55,57]. Surprisingly, both Re-N bond lengths; Re(1)-N(1) and Re(1)-N(1_a) are equal with the bond distance of 2.2238(17) \u0026Aring;. The two bonds fall within the range reported for similar rhenium-nitrogen bond distances in comparison to other rhenium(I) complexes in the literature whereby nitrogen coordinates as a saturated donor atom [44,50,57,58].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe bond length; Re(1)-Cl(1) [2.4715(16)\u0026Aring;] confirms that the bond length between rhenium and chloride in similar reported complexes [60]. In addition, the distances and angles of the rhenium- amine and CO groups confirm that compound \u003cstrong\u003e1\u003c/strong\u003e is in a good agreement with the reported organometallic compounds, tricarbonyl-rhenium chloride \u0026nbsp;of group 7 [60,61]. The three carbonyl ligands in a facial arrangement are a result of the formation of two equal non-linear \u003cem\u003etrans\u003c/em\u003e bond angles N(1)-Re(1)-C(2) and N(1_a) -Re(1)-C(2_a) with a bond angle of 175.16(8)\u0026deg;, and a third nonlinear angle Cl(1)-Re(1)-C(1) [175.25(17)\u0026deg;] which is close to the first two angles. The overall observation shows that all these \u003cem\u003etrans\u003c/em\u003e angle deviate from linearity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe coordinated H\u003csub\u003e2\u003c/sub\u003edpp \u0026nbsp;ligand had the possibility to coordinate as a N\u003csub\u003e4\u003c/sub\u003e-donor ligand. Surprisingly, it acted as \u0026nbsp;a bidentate N\u003csub\u003e2\u003c/sub\u003e-donor chelate leaving behind two uncoordinated nitrogen atoms. The C-N bond lenghts N(1)-C(3) [1.482(2)\u0026Aring;], N(1)-C(6) [1.494(3)\u0026Aring;], N(2)-C(3) [1.449(2)\u0026Aring;], N(2)-C(4) [1.474(3)\u0026Aring;] and N(2)-C(7) [1.467(3)\u0026Aring;] are all single bonds which confirm that all nitrogen atoms in the coordinated H\u003csub\u003e2\u003c/sub\u003edpp chelate are saturated, and bond around the rhenium(I) metal center as neutral atoms [44,57]. The C-N-C bond angles C(3)-N(1)-C(6), C(3)-N(2)-C(4), C(3)-N(2)-C(7) and C(4)-N(2)-C(7) of \u0026nbsp;109.50(15), 110.38(15), 109.01(17), 109.95(16), and 110.36(16) respectively are approximately equal, and also confirm that the corresponding bond distances in the fused rings \u0026nbsp;of the H\u003csub\u003e2\u003c/sub\u003edpp ligand are single bonds. \u0026nbsp;Interestingly, the dihedral angle determined by the least square plane as described by ligand backbone between carbon and nitrogen atoms of the ring in \u003cstrong\u003e1\u003c/strong\u003e;is C(4)-N(2)-C(7)-C(7_a) \u0026nbsp;[180.00(18)\u0026deg;]. Additionally, the torsion angles observed, Cl(1)-Re(1)-N(1)-C(6) [57.74(14)\u0026deg;], C(1)-Re(1)-N(1)-C(3) [107.6(2)\u0026deg;] and C(2_a)-Re(1)-N(1)-C(3) [-163.13(12)\u0026deg;] contributed to \u0026nbsp;the classical geometry of the molecule. \u0026nbsp;In addition to the coordination behaviour of the ligand, the molecular system and dimensions around the metal center in compound (\u003cstrong\u003e1\u003c/strong\u003e) are of high interest in the coordination behaviour of rhenium(I) of the \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e)]\u003csup\u003e+\u003c/sup\u003e. In addition to all interactions in the molecule, the full spatial distribution of the ligands around the central rhenium(I) atom contributing to its facial isomer configuration is occasionally used to describe the solid state of the crystal structure of this compound.\u003c/p\u003e\n\u003cp\u003eThe molecular packing in the unit cell analysis showed significant insights dominated by the intra-molecular and non-covalent interactions displayed among the asymmetric units in the molecular crystal system. Following the hydrogen bond data analysis of the crystal structure of compound \u003cstrong\u003e1\u003c/strong\u003e, the observed substantial contributions to the stability of crystal structure in the \u0026nbsp;packing of \u003cstrong\u003e1\u0026nbsp;\u003c/strong\u003eare N1-H1\u0026bull;\u0026bull;\u0026bull;Cl1 [3.170(2)\u0026Aring;] and N1-H1\u0026hellip;O2 [3.201(2)\u0026Aring;] interactions. The data from the crystal refinement revealed that C-H\u0026bull;\u0026bull;\u0026bull;O and N-H\u0026bull;\u0026bull;\u0026bull;O and N-H\u0026bull;\u0026bull;\u0026bull;Cl contacts also were involved in the stabilization of the geometry of the molecule as shown in the crystal packing (Table 1 and Figure 2). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1:\u0026nbsp;\u003c/strong\u003eHydrogen-bonds and molecular interactions (\u0026Aring;,\u0026ordm;) for \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e(H\u003csub\u003e2\u003c/sub\u003edpp)Cl] (\u003cstrong\u003e1\u003c/strong\u003e)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eD\u0026thinsp;\u0026minus;\u0026thinsp;H\u003csup\u003e\u0026hellip;\u003c/sup\u003eA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eD\u0026thinsp;\u0026minus;\u0026thinsp;H\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eH\u003csup\u003e\u0026hellip;\u003c/sup\u003eA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eD\u003csup\u003e\u0026hellip;\u003c/sup\u003eA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eD\u0026thinsp;\u0026minus;\u0026thinsp;H\u003csup\u003e\u0026hellip;\u003c/sup\u003eA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003eN1-H1\u0026hellip;Cl1\u003c/p\u003e\n \u003cp\u003eN1-H1\u0026hellip;O2\u003c/p\u003e\n \u003cp\u003eC7-H7B...O1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.82(2)\u003c/p\u003e\n \u003cp\u003e0.82(2)\u003c/p\u003e\n \u003cp\u003e0.9900\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2.78(2)\u003c/p\u003e\n \u003cp\u003e2.49(2)\u003c/p\u003e\n \u003cp\u003e2.5200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e3.170(2)\u003c/p\u003e\n \u003cp\u003e3.201(2)\u003c/p\u003e\n \u003cp\u003e3.441(5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e111.2(18)\u003c/p\u003e\n \u003cp\u003e145(2)\u003c/p\u003e\n \u003cp\u003e155.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e: Crystallographic data and structure refinement data for \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e(H\u003csub\u003e2\u003c/sub\u003edpp)Cl]\u003cstrong\u003e\u0026nbsp;(1\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"492\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 229px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 263px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCompound 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 229px;\"\u003e\n \u003cp\u003eChemical Formula\u003c/p\u003e\n \u003cp\u003eFormula weight\u003c/p\u003e\n \u003cp\u003eTemperature (K)\u003c/p\u003e\n \u003cp\u003eCrystal system\u003c/p\u003e\n \u003cp\u003eSpace group\u003c/p\u003e\n \u003cp\u003eUnit cell dimensions (\u0026Aring;, ˚)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eCrystal size/mm\u003csup\u003e3\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eVolume\u003c/em\u003e (\u0026Aring;\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eDensity (calc.) (g/m\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n \u003cp\u003eAbsorption coefficient (mm\u003csup\u003e-1\u003c/sup\u003e)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eF\u003c/em\u003e (000)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eRadiation\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026theta;\u003c/em\u003e range for data collection (deg)\u003c/p\u003e\n \u003cp\u003eIndex ranges\u0026nbsp;h,k,l max\u003c/p\u003e\n \u003cp\u003eReflections Measured\u003c/p\u003e\n \u003cp\u003eReflections collected Independent reflections\u003c/p\u003e\n \u003cp\u003eData/parameters\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eGoodness-of-fit on \u003cem\u003eF\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFinal R indexes [I\u0026gt;=2\u0026sigma; (I)]\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eLargest diff. peak and hole(e/\u0026Aring;\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 263px;\"\u003e\n \u003cp\u003eC\u003csub\u003e13\u003c/sub\u003eH\u003csub\u003e20\u003c/sub\u003eCl N\u003csub\u003e4\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003eRe\u003c/p\u003e\n \u003cp\u003e501.99\u003c/p\u003e\n \u003cp\u003e200 K\u003c/p\u003e\n \u003cp\u003eMonoclinic\u003c/p\u003e\n \u003cp\u003eI2/a \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp\u003ea=11.7704(6) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003cem\u003e\u0026alpha;\u003c/em\u003e = 90\u003c/p\u003e\n \u003cp\u003eb=10.8578(6) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003cem\u003e\u0026beta;\u003c/em\u003e =111.412(3)\u003c/p\u003e\n \u003cp\u003ec=13.5622(5) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003cem\u003e\u0026gamma;\u003c/em\u003e = 90\u003c/p\u003e\n \u003cp\u003e0.13 x \u0026nbsp;0.18 x \u0026nbsp; \u0026nbsp; 0.25\u003c/p\u003e\n \u003cp\u003e1613.63(14)\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e2.066\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7.713\u003c/p\u003e\n \u003cp\u003e968\u003c/p\u003e\n \u003cp\u003eMoK\u0026alpha; (\u0026lambda; = 0.71073 )\u003c/p\u003e\n \u003cp\u003e2.5 to 28.3\u003c/p\u003e\n \u003cp\u003e-15\u0026le;h\u0026le;15,-14\u0026le; k14,-18\u0026le; l\u0026le;18\u003c/p\u003e\n \u003cp\u003e1951\u003c/p\u003e\n \u003cp\u003e13705\u003c/p\u003e\n \u003cp\u003e2002\u003c/p\u003e\n \u003cp\u003e2002/118\u003c/p\u003e\n \u003cp\u003e1.23\u003c/p\u003e\n \u003cp\u003eR\u003csub\u003e1\u003c/sub\u003e =0.0112, wR\u003csub\u003e2\u003c/sub\u003e = 0.0247\u003c/p\u003e\n \u003cp\u003e0.44/-0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Selected bond lengths (\u003c/strong\u003e\u003cstrong\u003e\u0026Aring;\u003c/strong\u003e\u003cstrong\u003e) and bond angles (\u0026deg;) for\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1.\u003c/strong\u003e\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 582px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003cstrong\u003eBond lengths\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003eRe(1)-Cl(1)\u003c/p\u003e\n \u003cp\u003eRe(1)-N(1)\u003c/p\u003e\n \u003cp\u003eRe(1)-C(1)\u003c/p\u003e\n \u003cp\u003eRe(1)-C(2)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRe(1)-Cl(1_a)\u003c/p\u003e\n \u003cp\u003eRe(1)-N(1_a)\u003c/p\u003e\n \u003cp\u003eRe(1)-C(1_a)\u003c/p\u003e\n \u003cp\u003eRe(1)-C(2_a)\u003c/p\u003e\n \u003cp\u003eC(5)-C(6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e2.4715(16)\u003c/p\u003e\n \u003cp\u003e2.2238(17)\u003c/p\u003e\n \u003cp\u003e1.887(6)\u003c/p\u003e\n \u003cp\u003e1.909(2)\u003c/p\u003e\n \u003cp\u003e2.4715(16)\u003c/p\u003e\n \u003cp\u003e2.2238(17)\u003c/p\u003e\n \u003cp\u003e1.887(6)\u003c/p\u003e\n \u003cp\u003e1.909(2)\u003c/p\u003e\n \u003cp\u003e1.516(3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003eN(1)-C(3)\u003c/p\u003e\n \u003cp\u003eN(1)-C(6)\u003c/p\u003e\n \u003cp\u003eN(2)-C(3)\u003c/p\u003e\n \u003cp\u003eN(2)-C(4)\u003c/p\u003e\n \u003cp\u003eN(2)-C(7)\u003c/p\u003e\n \u003cp\u003eO(1)-C(1)\u003c/p\u003e\n \u003cp\u003eO(2)-C(2)\u003c/p\u003e\n \u003cp\u003eC(3)-C(3_a)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eC(4)-C(5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e1.482(2)\u003c/p\u003e\n \u003cp\u003e1.494(3)\u003c/p\u003e\n \u003cp\u003e1.449(2)\u003c/p\u003e\n \u003cp\u003e1.474(3)\u003c/p\u003e\n \u003cp\u003e1.467(3)\u003c/p\u003e\n \u003cp\u003e1.154(8)\u003c/p\u003e\n \u003cp\u003e1.157(3)\u003c/p\u003e\n \u003cp\u003e1.526(3)\u003c/p\u003e\n \u003cp\u003e1.514(3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 582px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u003cstrong\u003eBond Angles\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003eCl(1)-Re(1)-N(1)\u003c/p\u003e\n \u003cp\u003eCl(1)-Re(1)-C(1)\u003c/p\u003e\n \u003cp\u003eCl(1)-Re(1)-C(2)\u003c/p\u003e\n \u003cp\u003eCl(1)-Re(1)-Cl(1_a)\u003c/p\u003e\n \u003cp\u003eCl(1)-Re(1)-N(1_a)\u003c/p\u003e\n \u003cp\u003eCl(1)-Re(1)-C(2_a)\u003c/p\u003e\n \u003cp\u003eN(1)-Re(1)-C(1)\u003c/p\u003e\n \u003cp\u003eN(1)-Re(1)-C(2)\u003c/p\u003e\n \u003cp\u003eN(1)-Re(1)-N(1_a)\u003c/p\u003e\n \u003cp\u003eN(1)-Re(1)-C(1_a)\u003c/p\u003e\n \u003cp\u003eN(1)-Re(1)-C(2_a)\u003c/p\u003e\n \u003cp\u003eC(1)-Re(1)-C(2)\u003c/p\u003e\n \u003cp\u003eN(1_a)-Re(1)-C(1)\u003c/p\u003e\n \u003cp\u003eC(1)-Re(1)-C(1_a)\u003c/p\u003e\n \u003cp\u003eC(1)-Re(1)-C(2_a)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e86.33(6)\u003c/p\u003e\n \u003cp\u003e175.25(17)\u003c/p\u003e\n \u003cp\u003e94.03(7)\u003c/p\u003e\n \u003cp\u003e168.57(5)\u003c/p\u003e\n \u003cp\u003e84.76(6)\u003c/p\u003e\n \u003cp\u003e94.24(7)\u003c/p\u003e\n \u003cp\u003e90.00(18)\u003c/p\u003e\n \u003cp\u003e175.16(8)\u003c/p\u003e\n \u003cp\u003e77.61(6)\u003c/p\u003e\n \u003cp\u003e91.50(18)\u003c/p\u003e\n \u003cp\u003e97.61(8)\u003c/p\u003e\n \u003cp\u003e89.37(19)\u003c/p\u003e\n \u003cp\u003e91.50(18)\u003c/p\u003e\n \u003cp\u003e178.1(2)\u003c/p\u003e\n \u003cp\u003e89.23(19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003eN(1_a)-Re(1)-C(2)\u003c/p\u003e\n \u003cp\u003eC(1_a)-Re(1)-C(2)\u003c/p\u003e\n \u003cp\u003eC(2)-Re(1)-C(2_a)\u003c/p\u003e\n \u003cp\u003eCl(1_a)-Re(1)-N(1_a)\u003c/p\u003e\n \u003cp\u003eCl(1_a)-Re(1)-C(1_a)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Cl(1_a)-Re(1)-C(2_a)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;N(1_a)-Re(1)-C(1_a)\u003c/p\u003e\n \u003cp\u003eN(1_a)-Re(1)-C(2_a)\u003c/p\u003e\n \u003cp\u003eC(1_a)-Re(1)-C(2_a)\u003c/p\u003e\n \u003cp\u003eC(3)-N(1)-C(6) \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eC(3)-N(2)-C(4)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eC(3)-N(2)-C(7)\u003c/p\u003e\n \u003cp\u003eC(4)-N(2)-C(7)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eN(1)-C(3)-N(2)\u003c/p\u003e\n \u003cp\u003eCl(1_a)-Re(1)-C(2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e97.61(8)\u003c/p\u003e\n \u003cp\u003e89.23(19)\u003c/p\u003e\n \u003cp\u003e87.18(9)\u003c/p\u003e\n \u003cp\u003e86.33(6)\u003c/p\u003e\n \u003cp\u003e175.25(17)\u003c/p\u003e\n \u003cp\u003e94.03(7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;90.00(18)\u003c/p\u003e\n \u003cp\u003e175.16(8)\u003c/p\u003e\n \u003cp\u003e89.37(19)\u003c/p\u003e\n \u003cp\u003e109.50(15)\u003c/p\u003e\n \u003cp\u003e110.38(15)\u003c/p\u003e\n \u003cp\u003e109.01(17)\u003c/p\u003e\n \u003cp\u003e109.95(16)\u003c/p\u003e\n \u003cp\u003e110.36(16)\u003c/p\u003e\n \u003cp\u003e94.24(7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe synthesis of bioorganometallic compounds brings a strong motivation for the investigation of the potential application of the simple \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e moiety core in the pharmaceutical industry, biochemical applications and coordination chemistry of rhenium.. In this study, we have successfully synthesized, purified through crystalisation the novel Re-based tricarbonyl complex bearing a macromolecule-tetraamine chelate. The X-ray crystallography results of the obtained compound, \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e(H\u003csub\u003e2\u003c/sub\u003edpp)Cl] \u003cb\u003e(1)\u003c/b\u003e, showed that the metal fragment is coordinated to the ligand \u003cem\u003evia\u003c/em\u003e N,N\u0026prime;-donor atoms. To the best of our knowledge, the reported complex herein is the first example of an organometallic compound whereby the used crown chelate underwent ligand modification leading to a coordinated chelate with fused rings. In addition, the imine bonds were reduced to saturated amine nitrogens, and this is a crucial observation in the coordination chemistry of rhenium(I). Our future research study will be extended to the investigation of various biological applications of the compound \u003cb\u003e1\u003c/b\u003e, in addition to the characterization of the used ligand in this report as well as its coordination behaviour to other various rhenium and technetium cores.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eDeclaration of competing interest\u003c/h2\u003e\u003cp\u003eThe authors affirm that the work described in this paper has not been influenced by any competing interests.\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThe implementation of this research work was supported \u003cem\u003evia\u003c/em\u003e the collaboration between the University of Rwanda-College of Science and Technology, other various colleges of University of Rwanda, Nelson Mandela University, Word academy of Science \u003cem\u003evia\u003c/em\u003e the project; Research Grant Agreement (RGA) No. 20\u0026ndash;145 RG/CHE/AF/AC_I \u0026ndash; FR3240314142, as well as Uppsala University through the project research Grant application for 2019\u0026ndash;2021, Research Groups and Scientific Networks under ISP, Uppsala University.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAccording to the CRedit contribution taxonomy, G.H. performed the role of conceptualization, conducted laboratory work and wrote the main manuscript text. J.M. data curation, formal analysis and writing original draft. T.U played a role of validating the methodology prepared and reviewed all figures and schemes. TM. drafted and validated the experimental protocol. D.U. performed a role of conceptualization and reviewed the first draft. F.H. reviewed the systematic literature search. E.H and R.B. run the X-Ray crystallographic analysis of the compound. A.S.I. helped in data extraction. J.B.N. and J.B.H. helped in compilation of the manuscript, visualization, review and editing. T.G. supervised the research project, conceptualization, methodology, resources and writing-review and editing. In addition, all authors reviewed the Manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e\u003cp\u003eAll forms of support from the Department of Chemistry of the University of Rwanda-College of Science and Technology, and the Government of Rwanda towards this research study are highly acknowledged. We are also grateful to the Chemistry Department of the Nelson Mandela University for providing laboratory equipment used for X-ray crystallographic data analysis. We express our gratitude to past and present co-workers and collaborators: Prof. Roger Alberto, Prof. Ignace Gatare, Mr. Vedaste Nyandwi, Prof. Th\u0026eacute;oneste Muhizi, Prof. Denis Ndanguza, Dr. Jean Bernard Ndayambaje, Prof. Zenixole Richman Tshentu, Dr. Adeniyi S. Ogunlaja for their contribution, motivation, enthusiasm and valuable experimental efforts provided during the implementation of this research study.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThis article and all the supplementary materials containing all the information and data required to investigate the conclusions in the article are available and can be accessed *via* the CCDC 2237761. The dataset of our present research study is available in a structured database that is openly accessible. The Cambridge Crystallographic Data Centre has received crystallographic data for the chemical described here as Supporting Information. The dataset can be found at following link: https://info.ccdc.cam.ac.uk/email-subscribe.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eZhang JB, Wang XB, Jin C (2006) Synthesis of 99mTc(CO)\u003csub\u003e3\u003c/sub\u003e-NOET \u003cem\u003evia\u003c/em\u003e [99mTc(OH\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e precursor and comparative biological studies with 99mTcN-NOET. J Radioanal Nucl Chem 269(1):227\u0026ndash;230\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMindt T, Struthers H, Garcia-Garayoa E, Desbouis D, Schibli R (2007) Strategies for the development of novel tumor targeting technetium and rhenium radiopharmaceuticals. 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J Organomet Chem 907:121064\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBaumeister JE, Reinig KM, Barnes CL, Kelley SP, Jurisson SS (2018) Technetium and rhenium Schiff base compounds for nuclear medicine: syntheses of rhenium analogues to 99mTc-furifosmin. Inorg Chem 57(20):12920\u0026ndash;12933\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBinkley SL, Barone NV, Underwood AC, Milsted A, Franklin BR, Herrick RS, Ziegler CJ (2010) The synthesis and toxicity of tripodal tricarbonyl rhenium complexes as radiopharmaceutical models. J Inorg Biochem 104(6):632\u0026ndash;638\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKianfar E, Monkowius U, Portenkirchner E, Kn\u0026ouml;r G (2014) Synthesis and Characterization of Novel Re(BIAN)(CO)\u003csub\u003e3\u003c/sub\u003eCl Derivatives Including the First Example of a Water-soluble Tricarbonyl Rhenium(I) Complex with Bis(imino)acenaphthene Ligands. Z f\u0026uuml;r Naturforschung B 69(6):691\u0026ndash;698. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5560/znb.2014-4016\u003c/span\u003e\u003cspan address=\"10.5560/znb.2014-4016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHabarurema G, Mukiza J, Gerber TI, Mukabagorora T, Hosten EC, Betz R (2020) Imidazolidine ligands and their coordination behaviour towards the \u003cem\u003efac\u003c/em\u003e-[Re (CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e core: Unusual synthetic route, spectroscopic and X-Ray crystallographic characterization. J Organomet Chem 906:121033\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Schemes","content":"\u003cp\u003eSchemes 1 to 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-chemical-crystallography","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocc","sideBox":"Learn more about [Journal of Chemical Crystallography](http://link.springer.com/journal/10870)","snPcode":"10870","submissionUrl":"https://submission.nature.com/new-submission/10870/3","title":"Journal of Chemical Crystallography","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Macromolecule, rhenium(I), bidentate, pharmaceutical, X-Ray crystallography","lastPublishedDoi":"10.21203/rs.3.rs-7489965/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7489965/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe demand for the design of novel anticancer drugs for chemotherapy and radiotherapy purposes is pressing due to cancer spreading worldwide, which is affecting a great number of people across the world. Among other existing compounds in the cancer chemotherapy, rhenium and technetium complexes are particularly emerging in the pipeline, and they are being investigated because of their promising biological applications and minimal \u003cem\u003ein vivo\u003c/em\u003e toxicity. The coordination behaviour of various macromolecules around the \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e moiety has significantly contributed to the preparation of various radiopharmaceuticals and other compounds with a variety of specific applications. Herein, we report the synthesis and characterization of an unusual non-radioactive rhenium complex \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e(H\u003csub\u003e2\u003c/sub\u003edpp)Cl] (\u003cb\u003e1\u003c/b\u003e) that was isolated from the reaction of Re(CO)\u003csub\u003e5\u003c/sub\u003eCl with a crown macrocyclic tetraamine compound, (8\u003cem\u003eE\u003c/em\u003e,10\u003cem\u003eE\u003c/em\u003e)-1,4,8,11-tetraazacyclotetradeca-8,10-diene (H\u003csub\u003e2\u003c/sub\u003etazd) in toluene. This compound \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e(H\u003csub\u003e2\u003c/sub\u003edpp)Cl] (\u003cb\u003e1\u003c/b\u003e) was then crystallographically analysed using single X-ray diffraction techniques. The produced compound is a monomeric rhenium complex with H\u003csub\u003e2\u003c/sub\u003edpp coordinating neutrally as a bidentate \u003cem\u003eN\u003c/em\u003e,\u003cem\u003eN\u0026prime;\u003c/em\u003e-donor chelate. The unusual behavior observed in the crystal structure of (\u003cb\u003e1\u003c/b\u003e) is dominated by the ring rearrangement of the used H\u003csub\u003e2\u003c/sub\u003etazd ligand into the coordinated macromolecule chelate; dodecahydropyrimido[2',1':3,4]pyrazino[1,2-a]pyrimidine (H\u003csub\u003e2\u003c/sub\u003edpp) molecule. The coordinated amine ligand, H\u003csub\u003e2\u003c/sub\u003edpp is also a result of the intramolecular conversion process \u003cem\u003evia\u003c/em\u003e the reduction of imine bonds in H\u003csub\u003e2\u003c/sub\u003etazd, leadingd to a chelate with three fused rings in the structure of compound \u003cb\u003e1\u003c/b\u003e. These findings revealed that both H\u003csub\u003e2\u003c/sub\u003etazd and H\u003csub\u003e2\u003c/sub\u003edpp macromolecules could be a source of macrocyclic chelating agents suitable for the preparation of a wide range of rhenium(I)-based complexes with the \u003cem\u003efac\u003c/em\u003e-[Re(CO)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e+\u003c/sup\u003e moiety. The refinement of compound \u003cb\u003e1\u003c/b\u003e predicts the ring formation in the macrocyclic ligand, and this phenomenon is rare in the coordination chemistry of rhenium and was probably catalysed by rhenium(I) in the complex.\u003c/p\u003e","manuscriptTitle":"Organometallic complex of fac-[Re(CO) 3 ] + moiety with a modified tetraamine macroheterocyclic molecule dodecahydropyrimido[2',1':3,4]pyrazino[1,2-a]pyrimidine chelate: Synthesis and X-ray crystallography characterization","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-12 09:23:03","doi":"10.21203/rs.3.rs-7489965/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-24T19:35:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-01T05:18:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-01T05:18:16+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Chemical Crystallography","date":"2025-08-29T15:24:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-chemical-crystallography","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocc","sideBox":"Learn more about [Journal of Chemical Crystallography](http://link.springer.com/journal/10870)","snPcode":"10870","submissionUrl":"https://submission.nature.com/new-submission/10870/3","title":"Journal of Chemical Crystallography","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"5b28b06f-09db-4bf3-a73a-63227b7939a4","owner":[],"postedDate":"November 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-09T16:07:21+00:00","versionOfRecord":{"articleIdentity":"rs-7489965","link":"https://doi.org/10.1007/s10870-026-01085-6","journal":{"identity":"journal-of-chemical-crystallography","isVorOnly":false,"title":"Journal of Chemical Crystallography"},"publishedOn":"2026-03-04 15:59:53","publishedOnDateReadable":"March 4th, 2026"},"versionCreatedAt":"2025-11-12 09:23:03","video":"","vorDoi":"10.1007/s10870-026-01085-6","vorDoiUrl":"https://doi.org/10.1007/s10870-026-01085-6","workflowStages":[]},"version":"v1","identity":"rs-7489965","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7489965","identity":"rs-7489965","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}