A versatile strategy to develop sequence-defined conjugated macromolecules: a powerful tool towards tunable optoelectronic properties

A versatile strategy to develop sequence-defined conjugated macromolecules: a powerful tool towards tunable optoelectronic properties | 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 Article A versatile strategy to develop sequence-defined conjugated macromolecules: a powerful tool towards tunable optoelectronic properties Guy Koeckelberghs, Wout Milis, Janine Peeters, Robin Erkens, Pascal Gerbaux, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4610463/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Conjugated sequence-defined polymers represent a cutting-edge area of polymer science, merging the precision of biological macromolecules with the versatility of synthetic polymers and the unique properties of conjugated systems. While early reports focused on activation/deactivation strategies, this article presents the first orthogonal approach to developing sequence-defined conjugated macromolecules (CMs), incorporating a new monomer at each reaction step. In CMs, the primary monomer sequence meticulously determines the optoelectronic properties. Step-by-step, features such as structural defects, chain length, dispersity, functional groups, topology, and monomers used in the backbone, are carefully considered and controlled, with optical data provided to support the necessity of sequence-defined approaches in CMs. Additionally, a beyond state-of-the-art and repeatable modular approach is introduced, connecting different orthogonally developed sequences. This method enhances efficiency and accelerates the synthesis process, facilitating comprehensive structure-property analyses, paving the way for tunable materials with record-breaking properties. Physical sciences/Chemistry/Polymer chemistry/Conjugated polymers Physical sciences/Chemistry/Polymer chemistry/Polymer synthesis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Conjugated macromolecules (CMs) are incredibly interesting because of the processability and versatility of polymers combined with the electronic characteristics of inorganic semiconductors. 1 , 2 Their remarkable optoelectronic features make CMs highly attractive for various applications such as OFETs, 3 , 4 OLEDs, 3 , 5 photovoltaic cells, 6 , 7 thermoelectrics 8 , 9 and in nonlinear optics 10 . However, the properties of CMs are determined and severely hampered by a number of factors such as structural defects, dispersity, chain length, functional end-groups, topology and monomers used in the backbone. As a result, precision control of the monomer sequence is crucial in tuning the optoelectronic properties. 1 , 2 An impressive example of this precision synthesis is observed in biopolymers, such as DNA and peptides. Depending on the sequence of nucleobases or amino acids, the structure serves a totally different purpose. This observation in nature sparked scientists’ curiosity to mimic the absolute control of these biopolymers. For non-conjugated polymers, this journey began with Merrifield developing a method making peptides easily accessible and paving the way towards a new field of research i.e., sequence-defined macromolecules. 11 The last decades, the field of polymer science witnessed a surge of interest concerning the synthesis of polymers with precisely defined monomer sequences. Ever since, a plethora of synthetic strategies have been developed to obtain sequence-defined structures. One notable approach is based on single-unit monomer insertions (SUMI). 12 – 16 This strategy aims to reduce the reactivity of the growing chain ends commonly observed in classical reversible-deactivation radical polymerizations. While these methods focus on controlled radical polymerizations, alternative approaches involve one-by-one iterative syntheses typically following an activation/deactivation 17–20 pattern or an orthogonal approach 21 – 25 . Contrary to non-conjugated polymers, progress in conjugated systems is limited. Transition-metal-catalyzed transfer polycondensation has been widely studied, but is not the holy grail. 26 , 27 Inevitably associated with this controlled polymerization is the molar mass distribution, incorporation of defects, no absolute control of end-groups nor of precise monomer sequence which all exert a substantial impact on the properties. The last years, appealing examples of conjugated sequence-defined polymers have been published. However, these approaches use the activation/deactivation method either by converting a functional end-group to another functionality, 28 – 30 by implementing protection/deprotection strategies 31 – 35 or by temperature controlling. 36 , 37 Compared to non-conjugated systems, there is a lack of orthogonal alternatives. In this study, a novel and unique procedure is revealed based on orthogonal reactions incorporating a different monomer in each reaction step. Alongside the utilization of diverse building blocks to synthesize different sequences, also end-groups and topology are varied and their importance is demonstrated. Moreover, a beyond state-of-the-art and repeatable modular approach is proposed employing the frequently observed method of activation/deactivation to connect different orthogonally developed oligomer segments. As a consequence, a material can be improved by resynthesizing only one specific segment rather than the entire macromolecule and thus facilitating the overall synthesis. Step-by-step all features influencing the optoelectronic properties will be considered and controlled. First, a proof of principle is provided to verify the suggested approach which confirms the uniformity of the sequence, the absence of defects, and control of functional groups. Then, chiral monomers are applied to investigate the chiroptical properties and aggregation behavior depending on the monomer position within the sequence. Next, a multifunctional monomer is incorporated into the backbone, establishing topological changes influencing the conjugation length. In addition, a new monomer building block is introduced modifying the topology and conjugation length without disrupting the latter. Finally, the novel modular approach is revealed showing its power to boost proper structure-property analyses Results and Discussion To establish an orthogonal approach, two distinct non-interfering coupling reactions are essential. Consequently, it is imperative to employ AB and CD functionalized monomers whereby the A functionality exclusively reacts with function D, while functionality B solely reacts with function C. Frequently used reactions to link aromatic molecules are cross-coupling reactions. These reactions are metal catalyzed and typically involve an aryl halide and an organometallic compound. Because of the nature of the required reagents, such as aryl halides, only one cross-coupling reaction can be applied. Considering the wide applicability of the Suzuki-Miyaura cross coupling (SMCC) and the inexpensive and non-toxic nature of its reagents, this reaction was selected. 38 , 39 For the second coupling reaction, three different reactions were evaluated as potential candidates (SI S6) among which the Horner-Wadsworth-Emmons (HWE) emerged as the most reliable. 40 Due to the combination of the SMCC and HWE reactions, monomers featuring a bromide function and a phosphonate group on one hand, and a boronic ester and an aldehyde function on the other hand, have been devised. Both monomeric units follow a synthetic procedure based on well-known reactions with a shared intermediate (SI S11). The applied reaction sequence consists of a Williamson ether synthesis of hydroquinone followed by dibromination using bromine (Br 2 ). Subsequently, one bromide function is converted to an aldehyde with n -BuLi, DMF, and H + in a Bouveault reaction to obtain the intermediate of which both desired structures are generated. On one hand, the bromide function can be substituted to a boronic ester via a Miyaura borylation ( O // ). On the other hand, the aldehyde can be reduced to an alcohol, that can be converted into a chlorine function. The so-obtained benzylic chloride is subjected to the Arbuzov reaction affording the requisite phosphonate ( O ). In addition to the monomers required to enlarge the oligomer, a premeditated chosen starting molecule ( S ) has been designed from which the oligomers are synthesized. This starting molecule possesses a bromide functionality to ensure the unidirectional growth, but also a (protected) alcohol function providing a versatile end-group with numerous post-polymerization possibilities. The design of this compound is the result of a brief study aimed to identify the optimal starting molecule (SI S9). To enhance the solubility, and thus the kinetics of the first SMCC reaction, the hydroxyl group is temporarily protected as an acetate. In order to prevent any side reaction during the subsequent HWE chain elongation, the hydroxyl group is deprotected after the first coupling reaction (Fig. 1 ). After the optimization of both the monomer synthesis and coupling reactions, the first conjugated oligomer developed in an orthogonal approach is synthesized ( SO // OO // ). We are not only able to develop a tetramer in 79.4% overall yield, but also the purification proves to be fairly easy using crystallizations or precipitations only. Besides the starting molecule, which does not possess any side chains, the used monomers all possess octyl side chains because of the easier monomer synthesis owing to the linear character. However, to extend the potential of the new orthogonal approach, monomers with racemic 2-methylbutyl side chains are synthesized resulting in two sets of two monomers ( O // , O , M // ( rac ) , M( rac ) ). To show the versatility of the method, three additional oligomers with different sequences but identical compositions are synthesized ( SM // OO // ( rac ) , SO // OM // ( rac ) and SO // MO // ( rac ) ). As a result, four different aspects that determine the properties of conjugated polymers are controlled. Perfect end-group fidelity is realized with the hydroxyl group and the bromide function or aldehyde at the extremities of the macromolecule. In addition, classic characterization techniques such as SEC, 1 H-NMR and MALDI-HRMS unambiguously confirms the obtention of perfectly defined monomer sequences and defect-free structures with defined chain lengths. Next, the chain length of the oligomers is increased from tetramer to hexamer and a monomer with chiral (S)- 2-methylbutyl side chain is used ( M // ( S ) ). This chiral monomer is combined with the regular octyl side chain monomers to develop two chiral hexamers with a linear backbone ( SO // OM // OM // (S) and SM // OO // OM // (S) ), affording two optical isomers differing in sequence. With previous six different oligomers (racemic and chiral sequences), the first optical observations can be drawn regarding the influence of monomers used, chain length and end-groups via UV-vis and fluorescence spectroscopies. As expected, diversification of monomers by using different side chains does not affect the optical properties significantly. Therefore, the spectroscopic results of these phenyl-only oligomers are consistent and remains unchanged independent of the sequence. As the oligomer progresses from dimer to hexamer, the conjugation length increases stepwise because of the enhanced delocalization and increasing number of π-electrons, facilitated by the additional aromatic ring. The redshift induced by this extra monomer depends on two factors, namely the planarity of the backbone and the functional end-groups. Following a HWE reaction (odd sequences), a vinylene bond between two phenyl rings is incorporated leading to a planar conformation. In contrast to the HWE reaction, the direct biaryl bond after an SMCC reaction (even sequences) provokes a moderate rotation between the consecutive aromatic rings due to steric hinderance. Based on these two aspects, a more significant redshift is expected after a HWE reaction versus after an SMCC reaction. However, the push-pull system established within the oligomer following an SMCC reaction causes a strong redshift, highlighting the importance of functional end-groups on the properties of conjugated macromolecules (Fig. 2 ). In the fluorescence measurements, the parameters of interest are the Stokes shift and the full width at half maximum (FWHM) which provide information about the rigidity of the conjugated backbone. When both values are relatively high, it implies that the structures are rather flexible, and vice versa. After a HWE reaction (odd sequences), both numbers tend to be relatively small, while after an SMCC reaction (even sequences) the opposite is observed. This makes sense because an SMCC introduces a biphenyl structure, reducing the overall rigidity, while after a HWE reaction a more planar vinylene structure is incorporated enhancing the rigidity. However, compared to literature data where FWHM of circa 1200 cm − 1 are observed, our oligomers appear to be fairly flexible. 41 , 42 Besides these intriguing results in UV-vis and fluorescence spectroscopies, implementing chiral monomers permits to study the chiroptical properties. Circular dichroism (CD) is a widely applied technique in conjugated systems and offers the possibility to analyze the accompanying aggregation process. This aggregation can be induced in several ways of which the most frequently used method is a stepwise addition of a non-solvent to an oligomer solution. Experiments are performed in 1x10 mm quartz cuvettes with 70% of non-solvent composed of different ratios of methanol and water while isopropanol is used as good solvent. Unfortunately, both hexamers did not show any CD signal although the scattering observed in the UV-vis spectra clearly indicates aggregate formation (SI S162). Note that the hexamers do not appear as clear solids in their pure form, but rather in a glassy amorphous state. Therefore, the corresponding enantiomeric tetramers ( SM // OO // ( S ) and SO // OM // ( S ) ) are investigated as they do appear as clear powders (Fig. 3 ). Interestingly, the CD intensities are different and the signs of both signals are opposite which unambiguously proves the importance of the monomer sequence on the properties in conjugated macromolecules. Topology A next step in justifying the versatility of the newly revealed approach consists of introducing a multifunctional monomer into the sequence. This will vary the topology and is realized by the development of V 2 which contains two bromide functions to prolong the oligomer (Fig. 4 ). This trifunctional monomer is combined with the linear octyl monomers as well as the chiral monomer used earlier. As a result, three different structures are synthesized of which two isomeric hexamers with the trifunctional monomer at the fifth position ( SM // OO // V 2 M // (S) and SO // OM // V 2 M // (S) ) and one pentamer with the branching molecule at the third position ( SO // V 2 M // O (S) ). Again, the optical properties of both branched hexamers are in agreement, making the discussion applicable for both. In the hexamer structures, the UV-vis results are in line with the results of the linear equivalents up to the level of the pentamer. However, a blue shift of λ max is observed for the hexamers owing to the meta orientation of V 2 , which disrupts the conjugation of the oligomer backbone. Because of the branching molecule, the structure should not be seen as one single oligomer, but rather as a set of one pentamer and two dimers, reducing the overall conjugation length. The same story holds for the pentamer SO // V 2 M // O( S ) . Up to the trimer the results are analogous, the tetramer has no improved conjugation length and for the pentamer, only a slight increase can be noticed. The trend in the fluorescence results is also comparable with the data acquired for the linear counterparts. In the branched hexamer structures, however, the shift towards lower wavelength has the same origin as in the UV-vis results, the structure should not be perceived as one single oligomer, but rather as a set of one pentamer and two dimers. The same story holds for SO // V 2 M // O( S ) , where a clear shoulder is observed which closely resembles a combination of the corresponding dimer and trimer fluorescence. Note that the SO // V 2 M // ( S ) signal is, due to normalization, out of proportion as this sequence did not appear to be fluorescent. Likewise the linear hexamers, solvatochromism experiments are conducted on the branched sequences to study the CD signal and accompanying aggregation process. Again, both branched hexamers did not show any CD signal although scattering was observed in UV-vis. The reason might be the same as with the linear hexamers, as also the branched hexamers occur as viscous oils. Therefore, the same experiment was not performed on the branched pentamer SO // V 2 M // O ( S ) as this was even more oil-like. Bandgap modification To achieve a considerable impact on the optical properties, the bandgap of the oligomer backbone must be adjusted more significantly. While varying the alkoxy-side chain has a negligible effect on the bandgap, substantial modification can be achieved with a new monomer building block. Phenanthrene is an intriguing alternative not only due to its different aromaticity, but also because the position of the functional groups can be deliberately chosen. Instead of functionalized phenanthrene on the 2- and 7-position resulting in a linear backbone, functionalized phenanthrene on the 3- and 6-position introduces a bend of 120° along the backbone. Consequently, this modifies the topology more subtly without disrupting the conjugation within the oligomer. A new pair of phenanthrene monomers is synthesized with an identical combination of functional groups as the phenylene duplicates ( P and P // ), to develop three new oligomers differing in monomer sequences ( SP // OO // , SO // PO // and SO // OP // ) (Fig. 5 ). When observing the optical results in-depth, not only the shape but also the position of the spectra are different. The wavelength of maximum absorbance for the dimer and trimers are comparable to the phenyl oligomers, while the tetramers show a more diverse range of λ max . Also the fluorescence data is different with remarkable characteristics. First of all, the SP // dimer emission band is at significantly lower energy than the phenylene equivalents. The emission band of the successive SP // O trimer shifts to lower wavelength, indicating a less conjugated structure than the dimer. However, both trimers SP // O and SO // P are emitting at higher wavelengths in comparison to the phenyl analogues. This might demonstrate that phenanthrene enhances the conjugation more significantly in the excited state. A noteworthy result is the apparent mirror image between the absorbance and emission of the tetramers (Fig. 5 , bottom right). The sequence absorbing at the lowest wavelength tends to emit at the highest wavelength. Contrary, the sequence absorbing at the highest wavelength seems to emit at the lowest wavelength. Modular approach Previous results already show the importance of a sequence-defined synthesis for conducting accurate structure-property analyses. Resynthesizing entire oligomers to adjust the monomer sequence at only a few positions requires a tremendous amount of additional work. To tackle this drawback, a modular approach allows to rapidly perform a structure-property analysis. To achieve this theory, the activation/deactivation (protection/deprotection) method mentioned in the introduction is applied in combination with the orthogonal oligomer synthesis. As discussed earlier, the presence of the hydroxyl group at the start of the oligomer allows the possibility to conduct post-polymerization reactions. Considering this, a novel type of monomer is designed to serve as endcap molecule. This molecule will endfunctionalize the oligomer with a different functional group than the usual bromide or aldehyde function which is required for the orthogonal approach. More precisely, the hydroxyl group can be converted into a pseudohalide, such as a triflate group, and a phosphonate-boronic ester molecule ( E ) is developed as endcapper (Fig. 6 ). This enables the linkage of two distinct oligomers, one with the endcap molecule and one with a pseudohalide, via an SMCC reaction. As a result, different oligomer segments can be synthesized simultaneously, accelerating the synthesis of the predetermined sequence. Note that this is not limited to the coupling of only two oligomers but can be repeatedly performed. The resulting coupled oligomer again possesses a hydroxyl group and an aldehyde able to be converted or endcapped, respectively. To demonstrate this modular approach, two different structures are designed ( SO // OO // ESO // OO // and SO // V 2 E // OO // OS ). Again, both sequences are characterized with classic characterization techniques showing perfectly defined sequences and defect-free structures with precisely known chain lengths. In addition, the optical spectra undoubtedly show how connecting different segments influences the properties and thus showing the importance of this modular approach. Conclusion In this study, an orthogonal approach to synthesizing sequence-defined conjugated macromolecules based on the SMCC and HWE reactions is established. The combination of these reactions enables the synthesis of defect-free and precisely defined sequences of conjugated macromolecules. The proof of principle is demonstrated by synthesizing oligomers with different sequences and compositions, utilizing monomers with linear, racemic and chiral side chains. Optical properties of these oligomers are analyzed using UV-vis and fluorescence spectroscopies, revealing insights into the effects of chain lengths and end-groups on the conjugation and rigidity. The chiroptical properties are studied with circular dichroism, showing the different results of sequences with equal monomer composition. Additionally, the study explored the use of a multifunctional monomer to vary topology, showing consistent optical properties and demonstrating the robustness of the approach. Further, a new aromatic monomer is incorporated to modify the bandgap more significantly and subtly varying the topology without disrupting the conjugation. Again, the spectroscopic results emphasize the importance of defined monomer sequences as different results are obtained with same monomer compositions. Finally, a modular synthesis strategy is introduced, allowing for the rapid assembly of oligomers by linking distinct segments. This approach significantly expedited the synthesis process and provides a pathway for detailed structure-property analyses. The successful implementation of this orthogonal approach and modular strategy highlights its potential for creating well-defined conjugated macromolecules with tailored properties for advanced optical material applications. References Müllen, K. & Scherf, U. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4610463","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":320338119,"identity":"1b97bd27-7b65-4efd-8e5f-3c8a1d1cccee","order_by":0,"name":"Guy Koeckelberghs","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0003-1412-8454","institution":"KU Leuven","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Guy","middleName":"","lastName":"Koeckelberghs","suffix":""},{"id":320338120,"identity":"73db445c-e5c2-4c40-b890-6c0f3de3b56c","order_by":1,"name":"Wout Milis","email":"","orcid":"","institution":"KU Leuven","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wout","middleName":"","lastName":"Milis","suffix":""},{"id":320338121,"identity":"26d9a236-6c9f-45fb-ba9c-befc14ada500","order_by":2,"name":"Janine Peeters","email":"","orcid":"","institution":"KU Leuven","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Janine","middleName":"","lastName":"Peeters","suffix":""},{"id":320338122,"identity":"d01023ca-33ca-4200-bc91-6f14b6e301c5","order_by":3,"name":"Robin Erkens","email":"","orcid":"https://orcid.org/0000-0002-7960-1276","institution":"KU Leuven","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Robin","middleName":"","lastName":"Erkens","suffix":""},{"id":320338123,"identity":"48d104dc-cfcd-4058-8e35-be3ec8e5e894","order_by":4,"name":"Pascal Gerbaux","email":"","orcid":"","institution":"University of Mons","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Pascal","middleName":"","lastName":"Gerbaux","suffix":""},{"id":320338124,"identity":"04f83c5e-ef4d-40f8-8a9a-1cb28a761b15","order_by":5,"name":"Julien De Winter","email":"","orcid":"","institution":"University of Mons","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Julien","middleName":"","lastName":"De Winter","suffix":""}],"badges":[],"createdAt":"2024-06-20 08:51:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4610463/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4610463/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":61311860,"identity":"212844b3-9fdc-440f-b456-2baef8744ced","added_by":"auto","created_at":"2024-07-29 11:12:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":383472,"visible":true,"origin":"","legend":"\u003cp\u003eA) Illustration of the orthogonal reaction scheme with monomers used. The // denotes where the aldehyde monomer/double bond is incorporated in the backbone. B) Illustration of the starting molecule with a deprotection after the first coupling. C) Backbone of the different tetramers developed and a SEC and MALDI-HRMS graph of the SO\u003csub\u003e//\u003c/sub\u003eOO\u003csub\u003e//\u003c/sub\u003e sequence.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4610463/v1/471e5a2f05abbdca347f2535.png"},{"id":61312455,"identity":"dec69faf-75a0-43f1-8e8a-7e45e2611e8c","added_by":"auto","created_at":"2024-07-29 11:20:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":412730,"visible":true,"origin":"","legend":"\u003cp\u003eIllustration of the monomers used to develop linear chiral hexamers with the backbone shown in the middle. At the bottom a UV-vis spectrum of one hexamer on the left and the corresponding fluorescence spectrum on the right. In the table the λ\u003csub\u003emax\u003c/sub\u003e, Stokes shift and FWHM of a hexamer series is shown.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4610463/v1/8912ebfd432442b768eb4ab4.png"},{"id":61311873,"identity":"7f571d4a-911d-48d1-8278-1d9a91801345","added_by":"auto","created_at":"2024-07-29 11:12:45","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":335840,"visible":true,"origin":"","legend":"\u003cp\u003eUV-vis (top) and CD (bottom) spectra of two chiral tetramers (\u003cstrong\u003eSM\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e//\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003eOO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e//\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003e(S)\u003c/strong\u003e (left) and \u003cstrong\u003eSO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e//\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003eOM\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e//\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003e(S)\u003c/strong\u003e \u0026nbsp;(right)). The good solvent is IPA and the non-solvent is MeOH/H\u003csub\u003e2\u003c/sub\u003eO in a 7/3 ratio added to a percentage of 70 %.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4610463/v1/f74d5fd19f6be3ff6e23ce31.png"},{"id":61311877,"identity":"c91b63f1-7945-4759-97d0-37959b1bd2e3","added_by":"auto","created_at":"2024-07-29 11:12:47","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":589152,"visible":true,"origin":"","legend":"\u003cp\u003eOn top the chemical structures of the branching molecule \u003cstrong\u003eV\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sub\u003e and the backbone of the pentamer with the branching molecule on the 3\u003csup\u003eth\u003c/sup\u003e position and the backbone of the hexamer with the branching molecule on the 5\u003csup\u003eth\u003c/sup\u003e position. At the bottom, UV-vis (top) and fluorescence (bottom) spectra of a hexamer with \u003cstrong\u003eV\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sub\u003e at the 5\u003csup\u003eth\u003c/sup\u003e position (left) and pentamer wit \u003cstrong\u003eV\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sub\u003e at the 3\u003csup\u003eth\u003c/sup\u003e position (right).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4610463/v1/413cc4e80e0e34eebbdfc866.png"},{"id":61311876,"identity":"00d1818a-27f1-4a10-92b4-7328b056c394","added_by":"auto","created_at":"2024-07-29 11:12:46","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":707555,"visible":true,"origin":"","legend":"\u003cp\u003eSynthesized phenanthrene monomers on top with the three different oligomers containing a phenanthrene. At the bottom UV-vis (solid line) and fluorescence (dashed line) of the oligomers. In the right bottom corner comparison of the UV-vis and fluorescence data of the three tetramers.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-4610463/v1/a7a1763770d27273bd13da46.png"},{"id":61311861,"identity":"6e0e9eea-7ee3-484e-aec1-8dd500aab4bb","added_by":"auto","created_at":"2024-07-29 11:12:45","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":558387,"visible":true,"origin":"","legend":"\u003cp\u003eA) Synthesis of the different oligomer blocks based on the \u003cstrong\u003eSO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e//\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003eOO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e//\u003c/strong\u003e\u003c/sub\u003e sequence with the modular developed \u003cstrong\u003eSO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e//\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003eOO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e//\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003eESO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e//\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003eOO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e//\u003c/strong\u003e\u003c/sub\u003e as result. B) The modular approach applied on \u003cstrong\u003eSOV\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sub\u003e. C) SEC data (top) and UV-vis (bottom, solid line) and fluorescence data (bottom, dashed line) of the regarding modular sequences.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-4610463/v1/4555dc8b0bae49f0edc403b6.png"},{"id":61312460,"identity":"a067511e-b7e3-4d69-81ac-c61b3637df32","added_by":"auto","created_at":"2024-07-29 11:20:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3429172,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4610463/v1/a028fc62-48e9-4184-9154-2dc4470085be.pdf"},{"id":61312456,"identity":"e4ddd5a1-b267-496f-8e01-3d0342212710","added_by":"auto","created_at":"2024-07-29 11:20:46","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":19054586,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"SI.docx","url":"https://assets-eu.researchsquare.com/files/rs-4610463/v1/38927813d84959c916338459.docx"},{"id":61311871,"identity":"5eb06263-e01f-420f-8f00-c9e2c7b0db57","added_by":"auto","created_at":"2024-07-29 11:12:45","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":56879,"visible":true,"origin":"","legend":"\u003cp\u003eGraphical abstract\u003c/p\u003e","description":"","filename":"Graphicalabstract.png","url":"https://assets-eu.researchsquare.com/files/rs-4610463/v1/599065dbe1b8d75973317469.png"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"A versatile strategy to develop sequence-defined conjugated macromolecules: a powerful tool towards tunable optoelectronic properties","fulltext":[{"header":"Introduction","content":"\u003cp\u003eConjugated macromolecules (CMs) are incredibly interesting because of the processability and versatility of polymers combined with the electronic characteristics of inorganic semiconductors.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Their remarkable optoelectronic features make CMs highly attractive for various applications such as OFETs,\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e OLEDs,\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e photovoltaic cells,\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e thermoelectrics\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e and in nonlinear optics\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. However, the properties of CMs are determined and severely hampered by a number of factors such as structural defects, dispersity, chain length, functional end-groups, topology and monomers used in the backbone. As a result, precision control of the monomer sequence is crucial in tuning the optoelectronic properties.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e An impressive example of this precision synthesis is observed in biopolymers, such as DNA and peptides. Depending on the sequence of nucleobases or amino acids, the structure serves a totally different purpose. This observation in nature sparked scientists\u0026rsquo; curiosity to mimic the absolute control of these biopolymers.\u003c/p\u003e \u003cp\u003eFor non-conjugated polymers, this journey began with Merrifield developing a method making peptides easily accessible and paving the way towards a new field of research i.e., sequence-defined macromolecules.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e The last decades, the field of polymer science witnessed a surge of interest concerning the synthesis of polymers with precisely defined monomer sequences. Ever since, a plethora of synthetic strategies have been developed to obtain sequence-defined structures. One notable approach is based on single-unit monomer insertions (SUMI).\u003csup\u003e\u003cspan additionalcitationids=\"CR13 CR14 CR15\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e This strategy aims to reduce the reactivity of the growing chain ends commonly observed in classical reversible-deactivation radical polymerizations. While these methods focus on controlled radical polymerizations, alternative approaches involve one-by-one iterative syntheses typically following an activation/deactivation\u003csup\u003e17\u0026ndash;20\u003c/sup\u003e pattern or an orthogonal approach\u003csup\u003e\u003cspan additionalcitationids=\"CR22 CR23 CR24\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eContrary to non-conjugated polymers, progress in conjugated systems is limited. Transition-metal-catalyzed transfer polycondensation has been widely studied, but is not the holy grail.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Inevitably associated with this controlled polymerization is the molar mass distribution, incorporation of defects, no absolute control of end-groups nor of precise monomer sequence which all exert a substantial impact on the properties. The last years, appealing examples of conjugated sequence-defined polymers have been published. However, these approaches use the activation/deactivation method either by converting a functional end-group to another functionality,\u003csup\u003e\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e by implementing protection/deprotection strategies\u003csup\u003e\u003cspan additionalcitationids=\"CR32 CR33 CR34\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e or by temperature controlling.\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e Compared to non-conjugated systems, there is a lack of orthogonal alternatives.\u003c/p\u003e \u003cp\u003eIn this study, a novel and unique procedure is revealed based on orthogonal reactions incorporating a different monomer in each reaction step. Alongside the utilization of diverse building blocks to synthesize different sequences, also end-groups and topology are varied and their importance is demonstrated. Moreover, a beyond state-of-the-art and repeatable modular approach is proposed employing the frequently observed method of activation/deactivation to connect different orthogonally developed oligomer segments. As a consequence, a material can be improved by resynthesizing only one specific segment rather than the entire macromolecule and thus facilitating the overall synthesis.\u003c/p\u003e \u003cp\u003eStep-by-step all features influencing the optoelectronic properties will be considered and controlled. First, a proof of principle is provided to verify the suggested approach which confirms the uniformity of the sequence, the absence of defects, and control of functional groups. Then, chiral monomers are applied to investigate the chiroptical properties and aggregation behavior depending on the monomer position within the sequence. Next, a multifunctional monomer is incorporated into the backbone, establishing topological changes influencing the conjugation length. In addition, a new monomer building block is introduced modifying the topology and conjugation length without disrupting the latter. Finally, the novel modular approach is revealed showing its power to boost proper structure-property analyses\u003c/p\u003e"},{"header":"Results and Discussion","content":"\u003cp\u003eTo establish an orthogonal approach, two distinct non-interfering coupling reactions are essential. Consequently, it is imperative to employ AB and CD functionalized monomers whereby the A functionality exclusively reacts with function D, while functionality B solely reacts with function C. Frequently used reactions to link aromatic molecules are cross-coupling reactions. These reactions are metal catalyzed and typically involve an aryl halide and an organometallic compound. Because of the nature of the required reagents, such as aryl halides, only one cross-coupling reaction can be applied. Considering the wide applicability of the Suzuki-Miyaura cross coupling (SMCC) and the inexpensive and non-toxic nature of its reagents, this reaction was selected.\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e For the second coupling reaction, three different reactions were evaluated as potential candidates (SI S6) among which the Horner-Wadsworth-Emmons (HWE) emerged as the most reliable.\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eDue to the combination of the SMCC and HWE reactions, monomers featuring a bromide function and a phosphonate group on one hand, and a boronic ester and an aldehyde function on the other hand, have been devised. Both monomeric units follow a synthetic procedure based on well-known reactions with a shared intermediate (SI S11). The applied reaction sequence consists of a Williamson ether synthesis of hydroquinone followed by dibromination using bromine (Br\u003csub\u003e2\u003c/sub\u003e). Subsequently, one bromide function is converted to an aldehyde with \u003cem\u003en\u003c/em\u003e-BuLi, DMF, and H\u003csup\u003e+\u003c/sup\u003e in a Bouveault reaction to obtain the intermediate of which both desired structures are generated. On one hand, the bromide function can be substituted to a boronic ester via a Miyaura borylation (\u003cb\u003eO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e). On the other hand, the aldehyde can be reduced to an alcohol, that can be converted into a chlorine function. The so-obtained benzylic chloride is subjected to the Arbuzov reaction affording the requisite phosphonate (\u003cb\u003eO\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eIn addition to the monomers required to enlarge the oligomer, a premeditated chosen starting molecule (\u003cb\u003eS\u003c/b\u003e) has been designed from which the oligomers are synthesized. This starting molecule possesses a bromide functionality to ensure the unidirectional growth, but also a (protected) alcohol function providing a versatile end-group with numerous post-polymerization possibilities. The design of this compound is the result of a brief study aimed to identify the optimal starting molecule (SI S9). To enhance the solubility, and thus the kinetics of the first SMCC reaction, the hydroxyl group is temporarily protected as an acetate. In order to prevent any side reaction during the subsequent HWE chain elongation, the hydroxyl group is deprotected after the first coupling reaction (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAfter the optimization of both the monomer synthesis and coupling reactions, the first conjugated oligomer developed in an orthogonal approach is synthesized (\u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e). We are not only able to develop a tetramer in 79.4% overall yield, but also the purification proves to be fairly easy using crystallizations or precipitations only. Besides the starting molecule, which does not possess any side chains, the used monomers all possess octyl side chains because of the easier monomer synthesis owing to the linear character. However, to extend the potential of the new orthogonal approach, monomers with racemic 2-methylbutyl side chains are synthesized resulting in two sets of two monomers (\u003cb\u003eO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e, \u003cb\u003eO\u003c/b\u003e, \u003cb\u003eM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e(\u003c/b\u003e\u003cb\u003erac\u003c/b\u003e\u003cb\u003e)\u003c/b\u003e, \u003cb\u003eM(\u003c/b\u003e\u003cb\u003erac\u003c/b\u003e\u003cb\u003e)\u003c/b\u003e). To show the versatility of the method, three additional oligomers with different sequences but identical compositions are synthesized (\u003cb\u003eSM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e(\u003c/b\u003e\u003cb\u003erac\u003c/b\u003e\u003cb\u003e)\u003c/b\u003e, \u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e(\u003c/b\u003e\u003cb\u003erac\u003c/b\u003e\u003cb\u003e)\u003c/b\u003e and \u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eMO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e(\u003c/b\u003e\u003cb\u003erac\u003c/b\u003e\u003cb\u003e)\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eAs a result, four different aspects that determine the properties of conjugated polymers are controlled. Perfect end-group fidelity is realized with the hydroxyl group and the bromide function or aldehyde at the extremities of the macromolecule. In addition, classic characterization techniques such as SEC, \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003eH-NMR and MALDI-HRMS unambiguously confirms the obtention of perfectly defined monomer sequences and defect-free structures with defined chain lengths.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eNext, the chain length of the oligomers is increased from tetramer to hexamer and a monomer with chiral \u003cem\u003e(S)-\u003c/em\u003e2-methylbutyl side chain is used (\u003cb\u003eM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e(\u003c/b\u003e\u003cb\u003eS\u003c/b\u003e\u003cb\u003e)\u003c/b\u003e). This chiral monomer is combined with the regular octyl side chain monomers to develop two chiral hexamers with a linear backbone (\u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e(S)\u003c/b\u003e and \u003cb\u003eSM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e(S)\u003c/b\u003e), affording two optical isomers differing in sequence.\u003c/p\u003e \u003cp\u003eWith previous six different oligomers (racemic and chiral sequences), the first optical observations can be drawn regarding the influence of monomers used, chain length and end-groups via UV-vis and fluorescence spectroscopies. As expected, diversification of monomers by using different side chains does not affect the optical properties significantly. Therefore, the spectroscopic results of these phenyl-only oligomers are consistent and remains unchanged independent of the sequence.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAs the oligomer progresses from dimer to hexamer, the conjugation length increases stepwise because of the enhanced delocalization and increasing number of π-electrons, facilitated by the additional aromatic ring. The redshift induced by this extra monomer depends on two factors, namely the planarity of the backbone and the functional end-groups. Following a HWE reaction (odd sequences), a vinylene bond between two phenyl rings is incorporated leading to a planar conformation. In contrast to the HWE reaction, the direct biaryl bond after an SMCC reaction (even sequences) provokes a moderate rotation between the consecutive aromatic rings due to steric hinderance. Based on these two aspects, a more significant redshift is expected after a HWE reaction versus after an SMCC reaction. However, the push-pull system established within the oligomer following an SMCC reaction causes a strong redshift, highlighting the importance of functional end-groups on the properties of conjugated macromolecules (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn the fluorescence measurements, the parameters of interest are the Stokes shift and the full width at half maximum (FWHM) which provide information about the rigidity of the conjugated backbone. When both values are relatively high, it implies that the structures are rather flexible, and vice versa. After a HWE reaction (odd sequences), both numbers tend to be relatively small, while after an SMCC reaction (even sequences) the opposite is observed. This makes sense because an SMCC introduces a biphenyl structure, reducing the overall rigidity, while after a HWE reaction a more planar vinylene structure is incorporated enhancing the rigidity. However, compared to literature data where FWHM of circa 1200 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e are observed, our oligomers appear to be fairly flexible.\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e,\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eBesides these intriguing results in UV-vis and fluorescence spectroscopies, implementing chiral monomers permits to study the chiroptical properties. Circular dichroism (CD) is a widely applied technique in conjugated systems and offers the possibility to analyze the accompanying aggregation process. This aggregation can be induced in several ways of which the most frequently used method is a stepwise addition of a non-solvent to an oligomer solution.\u003c/p\u003e \u003cp\u003eExperiments are performed in 1x10 mm quartz cuvettes with 70% of non-solvent composed of different ratios of methanol and water while isopropanol is used as good solvent. Unfortunately, both hexamers did not show any CD signal although the scattering observed in the UV-vis spectra clearly indicates aggregate formation (SI S162). Note that the hexamers do not appear as clear solids in their pure form, but rather in a glassy amorphous state. Therefore, the corresponding enantiomeric tetramers (\u003cb\u003eSM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e(\u003c/b\u003e\u003cb\u003eS\u003c/b\u003e\u003cb\u003e)\u003c/b\u003e and \u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e(\u003c/b\u003e\u003cb\u003eS\u003c/b\u003e\u003cb\u003e)\u003c/b\u003e) are investigated as they do appear as clear powders (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Interestingly, the CD intensities are different and the signs of both signals are opposite which unambiguously proves the importance of the monomer sequence on the properties in conjugated macromolecules.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eTopology\u003c/h2\u003e \u003cp\u003eA next step in justifying the versatility of the newly revealed approach consists of introducing a multifunctional monomer into the sequence. This will vary the topology and is realized by the development of \u003cb\u003eV\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e which contains two bromide functions to prolong the oligomer (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). This trifunctional monomer is combined with the linear octyl monomers as well as the chiral monomer used earlier. As a result, three different structures are synthesized of which two isomeric hexamers with the trifunctional monomer at the fifth position (\u003cb\u003eSM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eV\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e(S)\u003c/b\u003e and \u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eV\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e(S)\u003c/b\u003e) and one pentamer with the branching molecule at the third position (\u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eV\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eO\u003c/b\u003e\u003cb\u003e(S)\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eAgain, the optical properties of both branched hexamers are in agreement, making the discussion applicable for both. In the hexamer structures, the UV-vis results are in line with the results of the linear equivalents up to the level of the pentamer. However, a blue shift of λ\u003csub\u003emax\u003c/sub\u003e is observed for the hexamers owing to the meta orientation of \u003cb\u003eV\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e, which disrupts the conjugation of the oligomer backbone. Because of the branching molecule, the structure should not be seen as one single oligomer, but rather as a set of one pentamer and two dimers, reducing the overall conjugation length. The same story holds for the pentamer \u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eV\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eO(\u003c/b\u003e\u003cb\u003eS\u003c/b\u003e\u003cb\u003e)\u003c/b\u003e. Up to the trimer the results are analogous, the tetramer has no improved conjugation length and for the pentamer, only a slight increase can be noticed.\u003c/p\u003e \u003cp\u003eThe trend in the fluorescence results is also comparable with the data acquired for the linear counterparts. In the branched hexamer structures, however, the shift towards lower wavelength has the same origin as in the UV-vis results, the structure should not be perceived as one single oligomer, but rather as a set of one pentamer and two dimers. The same story holds for \u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eV\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eO(\u003c/b\u003e\u003cb\u003eS\u003c/b\u003e\u003cb\u003e)\u003c/b\u003e, where a clear shoulder is observed which closely resembles a combination of the corresponding dimer and trimer fluorescence. Note that the \u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eV\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e(\u003c/b\u003e\u003cb\u003eS\u003c/b\u003e\u003cb\u003e)\u003c/b\u003e signal is, due to normalization, out of proportion as this sequence did not appear to be fluorescent.\u003c/p\u003e \u003cp\u003eLikewise the linear hexamers, solvatochromism experiments are conducted on the branched sequences to study the CD signal and accompanying aggregation process. Again, both branched hexamers did not show any CD signal although scattering was observed in UV-vis. The reason might be the same as with the linear hexamers, as also the branched hexamers occur as viscous oils. Therefore, the same experiment was not performed on the branched pentamer \u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eV\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eM\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eO (\u003c/b\u003e\u003cb\u003eS\u003c/b\u003e\u003cb\u003e)\u003c/b\u003e as this was even more oil-like.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eBandgap modification\u003c/h2\u003e \u003cp\u003eTo achieve a considerable impact on the optical properties, the bandgap of the oligomer backbone must be adjusted more significantly. While varying the alkoxy-side chain has a negligible effect on the bandgap, substantial modification can be achieved with a new monomer building block. Phenanthrene is an intriguing alternative not only due to its different aromaticity, but also because the position of the functional groups can be deliberately chosen. Instead of functionalized phenanthrene on the 2- and 7-position resulting in a linear backbone, functionalized phenanthrene on the 3- and 6-position introduces a bend of 120\u0026deg; along the backbone. Consequently, this modifies the topology more subtly without disrupting the conjugation within the oligomer. A new pair of phenanthrene monomers is synthesized with an identical combination of functional groups as the phenylene duplicates (\u003cb\u003eP\u003c/b\u003e and \u003cb\u003eP\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e), to develop three new oligomers differing in monomer sequences (\u003cb\u003eSP\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e, \u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003ePO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e and \u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOP\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhen observing the optical results in-depth, not only the shape but also the position of the spectra are different. The wavelength of maximum absorbance for the dimer and trimers are comparable to the phenyl oligomers, while the tetramers show a more diverse range of λ\u003csub\u003emax\u003c/sub\u003e. Also the fluorescence data is different with remarkable characteristics. First of all, the \u003cb\u003eSP\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e dimer emission band is at significantly lower energy than the phenylene equivalents. The emission band of the successive \u003cb\u003eSP\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eO\u003c/b\u003e trimer shifts to lower wavelength, indicating a less conjugated structure than the dimer. However, both trimers \u003cb\u003eSP\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eO\u003c/b\u003e and \u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eP\u003c/b\u003e are emitting at higher wavelengths in comparison to the phenyl analogues. This might demonstrate that phenanthrene enhances the conjugation more significantly in the excited state. A noteworthy result is the apparent mirror image between the absorbance and emission of the tetramers (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, bottom right). The sequence absorbing at the lowest wavelength tends to emit at the highest wavelength. Contrary, the sequence absorbing at the highest wavelength seems to emit at the lowest wavelength.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eModular approach\u003c/h2\u003e \u003cp\u003ePrevious results already show the importance of a sequence-defined synthesis for conducting accurate structure-property analyses. Resynthesizing entire oligomers to adjust the monomer sequence at only a few positions requires a tremendous amount of additional work. To tackle this drawback, a modular approach allows to rapidly perform a structure-property analysis. To achieve this theory, the activation/deactivation (protection/deprotection) method mentioned in the introduction is applied in combination with the orthogonal oligomer synthesis. As discussed earlier, the presence of the hydroxyl group at the start of the oligomer allows the possibility to conduct post-polymerization reactions. Considering this, a novel type of monomer is designed to serve as endcap molecule. This molecule will endfunctionalize the oligomer with a different functional group than the usual bromide or aldehyde function which is required for the orthogonal approach. More precisely, the hydroxyl group can be converted into a pseudohalide, such as a triflate group, and a phosphonate-boronic ester molecule (\u003cb\u003eE\u003c/b\u003e) is developed as endcapper (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). This enables the linkage of two distinct oligomers, one with the endcap molecule and one with a pseudohalide, via an SMCC reaction. As a result, different oligomer segments can be synthesized simultaneously, accelerating the synthesis of the predetermined sequence. Note that this is not limited to the coupling of only two oligomers but can be repeatedly performed. The resulting coupled oligomer again possesses a hydroxyl group and an aldehyde able to be converted or endcapped, respectively. To demonstrate this modular approach, two different structures are designed (\u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eESO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e and \u003cb\u003eSO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eV\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eE\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOO\u003c/b\u003e\u003csub\u003e\u003cb\u003e//\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eOS\u003c/b\u003e). Again, both sequences are characterized with classic characterization techniques showing perfectly defined sequences and defect-free structures with precisely known chain lengths. In addition, the optical spectra undoubtedly show how connecting different segments influences the properties and thus showing the importance of this modular approach.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this study, an orthogonal approach to synthesizing sequence-defined conjugated macromolecules based on the SMCC and HWE reactions is established. The combination of these reactions enables the synthesis of defect-free and precisely defined sequences of conjugated macromolecules. The proof of principle is demonstrated by synthesizing oligomers with different sequences and compositions, utilizing monomers with linear, racemic and chiral side chains. Optical properties of these oligomers are analyzed using UV-vis and fluorescence spectroscopies, revealing insights into the effects of chain lengths and end-groups on the conjugation and rigidity. The chiroptical properties are studied with circular dichroism, showing the different results of sequences with equal monomer composition. Additionally, the study explored the use of a multifunctional monomer to vary topology, showing consistent optical properties and demonstrating the robustness of the approach. Further, a new aromatic monomer is incorporated to modify the bandgap more significantly and subtly varying the topology without disrupting the conjugation. Again, the spectroscopic results emphasize the importance of defined monomer sequences as different results are obtained with same monomer compositions. Finally, a modular synthesis strategy is introduced, allowing for the rapid assembly of oligomers by linking distinct segments. This approach significantly expedited the synthesis process and provides a pathway for detailed structure-property analyses. The successful implementation of this orthogonal approach and modular strategy highlights its potential for creating well-defined conjugated macromolecules with tailored properties for advanced optical material applications.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eM\u0026uuml;llen, K. \u0026amp; Scherf, U. Conjugated Polymers: Where We Come From, Where We Stand, and Where We Might Go. \u003cem\u003eMacromolecular Chemistry and Physics\u003c/em\u003e vol. 224 2200337 (2023).\u003c/li\u003e\n\u003cli\u003eSwager, T. M. 50th Anniversary Perspective: Conducting/Semiconducting Conjugated Polymers. 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N-functionalized poly(dithieno[3,2-b:2\u0026prime;,3\u0026prime;-d]pyrrole)s: Highly fluorescent materials with reduced band gaps. \u003cem\u003eMacromolecules\u003c/em\u003e \u003cstrong\u003e39\u003c/strong\u003e, 1771\u0026ndash;1778 (2006).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4610463/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4610463/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eConjugated sequence-defined polymers represent a cutting-edge area of polymer science, merging the precision of biological macromolecules with the versatility of synthetic polymers and the unique properties of conjugated systems. While early reports focused on activation/deactivation strategies, this article presents the first orthogonal approach to developing sequence-defined conjugated macromolecules (CMs), incorporating a new monomer at each reaction step. In CMs, the primary monomer sequence meticulously determines the optoelectronic properties. Step-by-step, features such as structural defects, chain length, dispersity, functional groups, topology, and monomers used in the backbone, are carefully considered and controlled, with optical data provided to support the necessity of sequence-defined approaches in CMs. Additionally, a beyond state-of-the-art and repeatable modular approach is introduced, connecting different orthogonally developed sequences. This method enhances efficiency and accelerates the synthesis process, facilitating comprehensive structure-property analyses, paving the way for tunable materials with record-breaking properties.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e","manuscriptTitle":"A versatile strategy to develop sequence-defined conjugated macromolecules: a powerful tool towards tunable optoelectronic properties","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-29 11:12:39","doi":"10.21203/rs.3.rs-4610463/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"communications-chemistry","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"commschem","sideBox":"Learn more about [Communications Chemistry](http://www.nature.com/commschem/)","snPcode":"","submissionUrl":"","title":"Communications Chemistry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Communications Series","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"83c2cccc-8788-4423-9c60-b0a92ea9506b","owner":[],"postedDate":"July 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":33874647,"name":"Physical sciences/Chemistry/Polymer chemistry/Conjugated polymers"},{"id":33874648,"name":"Physical sciences/Chemistry/Polymer chemistry/Polymer synthesis"}],"tags":[],"updatedAt":"2024-07-29T11:12:39+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-29 11:12:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4610463","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4610463","identity":"rs-4610463","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}