Water oxidation is an important reaction studied as a way to generate electrons from water, to promote water splitting and the formation of green hydrogen. When using electrodes to drive homogeneous water oxidation catalysis, cyclic voltammograms are analyzed to provide catalytic rate constants. There are two main methods, foot-of-the-wave analysis (FOWA) and limiting current analysis. FOWA relies on approximations inherent to analyzing water oxidation catalysis, such as determining the formal potential of the catalytic intermediate, . Limiting current methods are the optimal way to analyze catalyst performance but rely on observable limiting current, which is virtually never seen in water oxidation. To avoid those issues, a method is proposed for analyzing nonideal cyclic voltammetry waveshapes in water oxidation: by analyzing rate data across a large range of potentials, an optimal potential, , can be obtained, where catalytic current, , is nearly independent of scan rate and has a linear dependency on buffer concentration. The method is applied to four homogeneous water oxidation catalysts with prior extensive electrochemical elucidation, all of which lack an ideal, purely kinetic waveshape in cyclic voltammetry. Application of the method avoids the biases of the other methods cited for the kinetic analyses of water oxidation catalysts.

Four ruthenium water oxidation catalysts that bear carboxylate and sulfonate groups in the active site have been synthesized and analyzed for their catalytic activity. The developed catalysts are modified from highly active species that traditionally have two carboxylate groups in the active site and are used to probe the effects of sulfonate substitution as well as the effects of other structural changes of the catalyst. The sulfonate-containing catalysts show higher electrochemical activity in pH 7 phosphate buffer with 3-5 times larger catalytic current, improved durability with sacrificial oxidant, and increased solubility compared to their dicarboxylate counterparts. Density functional theory calculations suggest that the sulfonate group provides more favorable geometry for water nucleophilic attack, of which is both the most energetically favorable mechanism calculated and experimentally predicted mechanism under electrochemical conditions. Further experimental studies have been performed to show that under certain conditions catalysts can perform well electrochemically under pH conditions as low as 1.6 and that various structural components can greatly change solubility and catalytic operation.

Carboxylate complexes have risen to prominence in the field of water oxidation catalysis. Here for the first time we use the higher valence of phosphinates [P(V)] relative to that of carboxylates [C(IV)] to increase ligand denticity. We describe the synthesis and characterization of a new dianionic pentadentate ligand, bcpq2- that contains a tridentate 2,2'-bipyridine-6-carboxylato moiety, in addition to a 6'-phosphinato substituent that acts as fourth ligand and bears a side arm containing a quinoline, the fifth ligand. The new bcpq ligand allows formation of [Ru(II)(bcpq)(L)] (2 a-b, L=picoline or isoquinoline) and in preliminary results, of a Co(II) complex. NMR spectroscopy, X-ray diffraction, cyclic voltammetry, differential pulse and square wave voltammetry were used to characterize 2 a-b, with 2 b being characterized more extensively as a catalyst. Bulk electrolysis over 15 h at pH 7 was also used, showing that 2 b gave 100 +/- 5 % faradaic efficiency and remained completely homogeneous, whereas 1 b was no longer homogeneous; this comparison conclusively shows the advantage of the added denticity in the electrocatalytic context. Replacing carboxylate with P(V) phosphinate with an added arm may be used in other ligand systems to enhance the durability of homogeneous catalysts. In this work, we use a higher valence of phosphinates [P(V)] relative to that of carboxylates [C(IV)] to increase ligand denticity to modify a ruthenium water oxidation catalyst. Interestingly, the increased ligand denticity greatly enhanced the durability of the ruthenium-based water oxidation catalyst, thus maintaining its homogeneous nature.+# image

We report a practical, light-mediated perfluoroalkylation using Langlois' reagent (sodium trifluoromethylsulfinate) that proceeds in the absence of any photocatalyst or additives. This method has allowed for the facile functionalization of pyridones and related N-heteroarenes such as azaindole. This protocol is operationally simple, uses readily available materials, and is tolerable for electron-neutral and -rich functional pyridones. Cyclic voltammetry was utilized as a mechanistic probe, and preliminary data suggest the reaction may involve an electrophilic radical mechanism.

H-bonds can exert a substantial impact on the course of organic electrode reactions due to their ability to stabilize charged intermediates and products formed during these reactions, as well as facilitate proton-coupled electron transfer (PCET) reactions. This has fundamental implications for the mechanism of organic electrode reactions, but also practical impact in supramolecular chemistry and potentially synthetic electrochemistry. My group's main focus has been on the supramolecular applications, using electron transfer to alter the strength of H-bonds to create highly redox-responsive H-bond dimers. Initially we sought to avoid proton transfer because we feared that would lead to irreversible electrochemistry. However, inevitably proton transfer did show up, but, to our surprise, did not lead to irreversible electrochemistry. To explain this, we developed a new mechanism, the "wedge scheme", that shows how H-bonding can facilitate reversible electron and proton transfer. This insight recently led us to a new PCET-based design strategy for the creation of our most highly redox-responsive H-bond dimers yet.

Unlike conventional polymers, in which monomers are reacted to form strong covalent connections, supramolecular polymers are formed by linking together monomers via weaker, non-covalent interactions such as H-bonds, ion-dipole interactions and so on. One very well-studied class of supramolecular polymers are based on the ureidopyrimidones, UPy’s, which dimerize via 4 strong, linear H-bonds in non-competitive solvents. Monomers for supramolecular polymerization can be made by linking together 2 or more UPy units with short covalent chains. Under dimerization conditions, the UPy’s link up to form longer polymeric chains. One of the useful attributes of such polymers is their self-healing ability. Application of heat or mechanical stress will readily break the monomers apart at the H-bonds, but, upon cooling or relief of stress, the bonds reform. The goal of this research is to see if electron transfer can be used as an alternative, more selective stimulus to break apart the UPy chains. As a first step in this direction, the use of our previously studied electroactive UPy’s, 1a and 1b, are being investigated as redox-active chain terminators. For these studies the known UPy monomer, 2, was synthesized. Viscosity measurements of solutions of 2 in 0.1 M NBu4PF6/CH2Cl2 give a critical polymerization concentration of 20 mM. Based on this, 60 mM 2 was chosen as the working concentration for initial experiments giving a solution with a specific viscosity of 3.0 mPa∙s. Upon addition of 2 mM of the ferrocene containing UPy 1a, the viscosity dropped to 1.1 mPa∙s, indicating that 1a is an effective chain terminator, decreasing the lengths of the chains which results in a decrease in the viscosity of the solution The ferrocenes were then completely oxidized to the ferrocenium form in a two compartment electrochemical cell. This caused the viscosity of the solution to increase from 1.0 to 1.7 mPa∙s, suggesting decreased effectiveness of the ferrocenium form as a chain terminator. This is consistent with poorer binding of the ferrocenium form to the bis-UPy. Importantly, reduction back to the ferrocene led to a decrease in the viscosity back to close to where it was initially. In this presentation, the results of further studies on the ability of both 1a and 1b to act as redox-responsive chain terminators for UPy-based supramolecular polymers will be reported. Figure 1

Recently we have reported a new strategy to create highly redox-responsive H-bond dimers based on proton-coupled electron transfer.1 The strategy capitalizes on the importance of secondary H-bonds in determining overall binding strength in H-bond dimers. Specifically, this study shows that electron-transfer induced proton transfer across a H-bond can be used to significantly strengthen the overall binding by both creating strong ionic H-bonds and by changing the secondary H-bonds from unfavorable to favorable. The power of this approach is demonstrated with the electroactive DAD (A = H-acceptor, D = H-donor) array 1 paired with the electroinactive ADA array 2. NMR titration in 0.1 M NBu4PF6/CD2Cl2 gives a Kassoc of 500 M− 1 in the starting oxidized state, a value typical of DAD-ADA dimers. However, upon two electron reduction in 0.1 M NBu4PF6/CH2Cl2, CV studies indicate a 1.8×105 increase in binding strength, corresponding to a very large Kassoc of 9×107 M− 1. The latter value is typical of DDD-AAA H-bond dimers, consistent with proton transfer across the central H-bond upon reduction. In this presentation, the results of a full investigation of this system will be reported, including UV-vis spectroelectrochemical studies that support proton transfer and NMR studies of possible 1-1 and 2-2 homodimerization. Furthermore, theoretical CV’s that include, if needed, homodimerization will be fit to the experimental CV’s to provide a more exact measure of the binding enhancement in this system. 1H. Choi, K. Baek, S. Toenjes, J. L. Gustafson, and D. K. Smith, J. Am. Chem. Soc. 2020, 142, 17271-17276. DOI: 10.1021/jacs.0c07841 Figure 1

Supramolecular polymers are constructed along weaker, non-covalent interactions such as hydrogen-bonding. Compared to conventional polymers where monomer units react to form covalent bonds, non-covalent interactions of monomer units grant these supramolecular polymers dynamic behavior. One example of these systems that utilizes non-covalent interactions to construct supramolecular polymers are the well-investigated ureidopyrimidinones, UPy. UPy’s dimerize along their 4 strong directional hydrogen bonds in non-polar organic solvents. UPy’s have been covalently linked at the ends of smaller monomer chains so as to function as chain-linkers in the construction of larger polymer structures under favorable dimerization conditions. One interest in the use of these systems in supramolecular applications is their inherent ability of self-healing. Applying heat or mechanical stress to these systems will prevent polymerization at the H-bonds. However, upon relief of these external stimuli, H-bonding resumes. In this study, the use of electron transfer as an external stimulus to perturb dimerization and affect UPy chain polymerization will be explored. In order to exemplify the aims of this study, previously studied electroactive UPy’s will be investigated as redox-responsive chain terminators with regards to linear polymer chains that are functionalized with UPy units at their terminal ends, allowing for long-chain polymerization indicated by an increase in solution viscosity. In this study, a decrease in solution viscosity should be observed once these long chain bi-functionalized UPy polymers are in the presence of redox-responsive mono-functional UPy. Upon electrochemical oxidation / reduction of the mono-functional electroactive UPy units, an increase in viscosity is expected. The weakened H-bonding of the mono-functional UPy units will prevent chain termination and long-chain polymerization between bi-functional long chain UPy’s is expected to resume.

Giardiasis and other protozoan infections are major worldwide causes of morbidity and mortality, yet development of new antimicrobial agents with improved efficacy and ability to override increasingly common drug resistance remains a major challenge. Antimicrobial drug development typically proceeds by broad functional screens of large chemical libraries or hypothesis-driven exploration of single microbial targets, but both strategies have challenges that have limited the introduction of new antimicrobials. Here, we describe an alternative drug development strategy that identifies a sufficient but manageable number of promising targets, while reducing the risk of pursuing targets of unproven value. The strategy is based on defining and exploiting the incompletely understood adduction targets of 5-nitroimidazoles, which are proven antimicrobials against a wide range of anaerobic protozoan and bacterial pathogens. Comprehensive adductome analysis by modified click chemistry and multi-dimensional proteomics were applied to the model pathogen Giardia lamblia to identify dozens of adducted protein targets common to both 5'-nitroimidazole-sensitive and -resistant cells. The list was highly enriched for known targets in G. lamblia, including arginine deiminase, α-tubulin, carbamate kinase, and heat shock protein 90, demonstrating the utility of the approach. Importantly, over twenty potential novel drug targets were identified. Inhibitors of two representative new targets, NADP-specific glutamate dehydrogenase and peroxiredoxin, were found to have significant antigiardial activity. Furthermore, all the identified targets remained available in resistant cells, since giardicidal activity of the respective inhibitors was not impacted by resistance to 5'-nitroimidazoles. These results demonstrate that the combined use of click chemistry and proteomics has the potential to reveal alternative drug targets for overcoming antimicrobial drug resistance in protozoan parasites.

The storage of solar energy in chemical bonds will depend on pH-universal catalysts that are not only impervious to acid, but actually thrive in it. Whereas other homogeneous water oxidation catalysts are less active in acid, we report a catalyst that maintained high electrocatalytic turnover frequency at pH values as low as 1.1 and 0.43 ( k cat =1501±608 s −1 and 831±254 s −1 , respectively). Moreover, current densities, related to catalytic reaction rates, ranged from 15 to 50 mA cm −2  mM −1 comparable to those reported for state-of-the-art heterogeneous catalysts and 30 to 100 times greater than those measured for two prominent literature homogeneous catalysts at pH 1.1 and 0.43. The catalyst also exhibited excellent durability when a chemical oxidant was used (Ce IV , 7400 turnovers, TOF 0.88 s −1 ). Preliminary computational studies suggest that the unusual active-site sulfonate group acts a proton relay even in strong acid, as intended.

We report studies on the photocatalytic formation of C–S bonds to form benzothiazoles via an intramolecular cyclization and sulfenylated indoles via an intermolecular reaction. Cyclic voltammetry (CV) and density functional theory studies suggest that benzothiazole formation proceeds via a mechanism that involves an electrophilic sulfur radical, while the indole sulfenylation likely proceeds via a nucleophilic sulfur radical adding into a radical cationic indole. These conditions were successfully extended to several thiobenzamides and indole substrates.

The kinetics of many proton-coupled electron transfer (PCET) reactions cannot be adequately described by step-wise proton and electron transfer. Concerted electron-proton transfer (CPET) is another possibility, but examples exist where step-wise mechanisms are not viable yet there is no compelling evidence for CPET. This study investigates such a reaction, the oxidation of an NH-containing phenylenediamine radical cation, H2PD+, in the presence of pyridines in acetonitrile. H2PD+ is formed by a net one electron oxidation of 2,3,5,6-tetramethylphenylenediamine in acetonitrile via a rather complicated mechanism that likely proceeds through a H-bonded dimer. Once formed, it can be further oxidized at more positive potentials to the quinoidal dication, H2PD2+, which will be considerably more acidic than the radical cation. Indeed, the E1/2 for the radical oxidation jumps to a considerably more negative potential upon addition of 1 equivalent of the weak base pyridine. The CV wave broadens but stays chemically reversible. Further addition of pyridine leads to smaller E1/2 shifts with continued reversibility. This behavior could possibly be explained by stabilization of H2PD2+ through H-bonding or proton transfer to pyridine, however, UV-vis spectroelectrochemical experiments provide definitive evidence for proton transfer. Furthermore, CV studies with 4-substituted pyridine derivatives of weaker basicity show that the observed E1/2 with 1 equivalent of the pyridine depends in a Nernstian fashion on the pKa of the conjugate acid of the pyridine, indicating that all the pyridines studied deprotonate H2PD2+ to give the quinoidal cation, HPD+. The continued E1/2 shift observed upon further addition of the pyridines can then be completely explained by application of the Nernst equation to the overall reaction H2PD+ + pyr → HPD+ + Hpyr+ + e−. However, while this explains the thermodynamics, the classic step-wise proton-electron transfer mechanism for this reaction cannot explain the observed reversibility at high base concentration. In contrast, the reversibility can be explained by a “wedge” scheme mechanism in which electron and proton transfer occur within the H-bond complex formed as an intermediate in proton transfer. In this case, the electron-proton transfer could be concerted, however, the kinetics for the second oxidation in the presence of pyridine show no significant isotope effect. Furthermore, a new reduction peak that appears at faster scan rates suggests the presence of an intermediate in the electron-proton transfer. Both results strongly suggest that the electron-proton transfer is step-wise, not concerted, within the H-bond complex. This result points to the important role H-bonding may play in PCET even without CPET.

Ureidopyrimidones (UPy’s) are well-known to dimerize in weakly polar solvents such as CH2Cl2, via the formation of four strong, linear H-bonds. This, coupled with their relative ease of synthesis, has led to their use as a linker in supramolecular polymers and gels. The attraction of such materials is their inherent self-healing properties, whereby a defect can be repaired by using heat or mechanical stress to reversibly break the polymer at the H-bond sites. This increases the fluidity of the material, allowing the defect to fill in. Upon cooling or relief of stress, the H-bonds reform and the defect is repaired. However, while the use of heat or mechanical stress as stimuli are clearly useful, neither is inherently very selective. On-going research in our lab is focused on increasing the versatility of the UPy system by creating electroactive UPy’s in which dimerization strength can be controlled in a more selective manner through oxidation and reduction. Previously, our group has shown that dimers based on the ferrocene-UPy derivative, 1, break apart upon oxidation of the ferrocene to the ferrocenium form at mM concentrations in CH2Cl2. This could be due both to the creation of electrostatic repulsion and a decrease in H-bond strength due to the reduced H-donor ability of the O and N on the pyrimidone side. In this project, another Fc-UPy has been prepared, 2, in which the ferrocene is attached to the urea side of the molecule. In contrast to 1, oxidation of 2 shows a single reversible ferrocene CV wave in CH2Cl2 at mM concentrations. Under these conditions, 1H NMR indicates that 2 is fully dimerized, thus, it appears that, unlike with 1, oxidation has no significant effect on dimerization of 2. In both cases, oxidation would increase electrostatic repulsion. However, unlike in 1, oxidation of 2 should actually increase H-bond strength by making the urea NH a stronger H-donor. Therefore, it appears that the effect of oxidation on the H-donating or accepting ability is a more crucial factor for dimerization control than electrostatics in these systems. Figure 1

Strength and directionality are the hallmark characteristics of binding for molecules with multiple hydrogen bonds. This is important in the area of molecular recognition and supramolecular construction. When coupled to a redox center, oxidation or reduction can affect hydrogen bonds by either strengthening or weakening bonding, and thus allow for greater control over this type of binding. One class of model compounds which can be used to investigate the effects of manipulating the characteristics of hydrogen bonding are bi-substituted ureas. An example previously studied in our group is 1-phenyl-3-(4-dimethylamino)phenylurea (UHH), which has a H-donor-donor (DD) motif. This compound was coupled with two guests that have a H-acceptor-acceptor (AA) motif, 1,4-dimethylpiperizine-2,3-dione (PZD) and 1,8-naphthyridine (naph), to investigate the effects of oxidation on hydrogen binding. Cyclic voltammetry (CV) of UHH in the presence of PZD in methylene chloride shows a reversible, one electron oxidation wave whose E1/2 shifts negative with an increase in concentration of PZD. This indicates an increase in hydrogen binding strength upon oxidation. It was originally thought to be due to stronger binding to the UHH radical cation, but additional CV investigations of isolated UHH revealed that it actually undergoes a two electron per two urea process as shown in equation 1 to give the doubly oxidized UH+ plus the protonated, still reduced, HUHH+. Since only HUHH+ retains the DD motif, it is more likely that it is strong H-bonding between HUHH+ and PZD that cause the observed potential shift. Analyzing the potential shift data based on this assumption gives binding constants Kred = 30 M−1 and Kox =700 M−1. In contrast to PZD, CV studies of UHH in the presence of naph show the current for the oxidation increases with little change in E1/2. This is rationalized by proton transfer from the UHH radical cation to the naph rather than the dimethylamino group on a reduced UHH, equation 2. This allows full oxidation of all the UHH, but results in conversion of the more favorable DD-AA H-bond motif to the less favorable AD-DA plus creates electrostatic repulsion. These effects counteract the increased acidity caused by oxidation, apparently resulting in no significant change in H-bonding strength. In new studies, the phenylenediamine redox center in UHH has been replaced with a ferrocene redox center, producing the compound 1-ferrocenyl-3-phenylurea (FcUHH). This change limits the oxidation to a one electron process, equation 3, and removes the basic site that facilitates proton transfer. Initial CV experiments of FcUHH and PZD in methylene chloride show a reversible, one electron oxidation with a corresponding negative shift in E1/2 with increasing concentration of PZD. The magnitude of the shift is comparable to UHH with PZD, and analysis of this data gives binding constants Kred = 80 M−1 and Kox = 500 M−1. Since oxidation of the ferrocene to ferrocenium produces a +1 charge, as does protonation of the dimethyamino group of UHH, the similarity of this result to that observed with UHH and PZD supports the hypothesis that the potential shifts observed with UHH and PZD are due to H-bonding with the protonated, reduced urea. Similar studies will be performed with FcUHH and naph for comparison to the UHH and naph result. One complication in the studies with FcUHH is that, to date, we have been unable to fully remove a small amount of 1,3-diphenylurea side-product. Since the N-H’s in FcUHH and 1,3-diphenylurea likely have similar polarity and thus affinity for PZD and naph, our existing binding constant measurements are flawed due to competition between FcUHH and diphenylurea for binding to the guest. This issue is currently being addressed with NMR titrations of 1,3-Diphenylurea with PZD and naph to measure these binding constants. This will allow a more accurate mathematical model to be constructed to fit the potential shift data for FcUHH and the guests. Moving forward, we hope to optimize the reaction conditions for the synthesis of FcUHH to prevent formation of the diphenylurea. However, whether we are successful with this or not, it is clear that the studies with FcUHH will provide an interesting and informative comparison to the earlier work with UHH and add to our understanding of redox-dependent H-bonding in general. Figure 1

An important class of supramolecular systems are those capable of forming dimers held together by multiple linear H-bonds. Of these, the 4 H-bond arrays based on the ureidopyrimidone or UPy unit have found particularly use, having the right combination of ease-of-synthesis and appropriate binding strengths to be useful for the formation of supramolecular polymers and gels. The selling points for these materials are there self-healing properties. By application of heat or mechanical stress the polymer chains will break reversibly at the H-bonds making the material more fluid and allowing a defect to fill in. Upon cooling or relief of the mechanical stress, the H-bonds re-form locking the repair in place. For many applications the use of heat or mechanical stress as the external signal to alter structure is perfect, however, for other applications, a more selective stimulus such as electron transfer would be advantageous. To do this, a reversible redox couple needs to be attached to the UPy in such a way that oxidation or reduction perturbs the H-bond strength. Over the last several years, we have synthesized and investigated the electrochemistry of several such systems, shown below. With UPyH, there is a phenylenediamine redox couple attached to the urea allowing perturbation of the H-donating ability of the urea NH. In the other examples, the redox couple, either a pyridinium [UPy(MeP+)] or a ferrocene [UPy(Fc)], is attached to the pyrimidone ring, allowing perturbation of the H-accepting ability of the pyrimidine N and O. In addition to their potential use in redox-responsive supramolecular materials, these compounds also provide good platforms for fundamental investigations on the role of H-bonding in proton-coupled electron transfer. Indeed, our studies show that with both UPyH and UPy(MeP+) electron transfer leads to proton transfer, resulting in interesting, albeit rather complicated electrochemistry. In both these cases, electron transfer would be expected to increase H-bond strength. In contrast, with UPy(Fc), oxidation should decrease H-bond strength. The result is no proton transfer and greatly simplified electrochemistry, which is more amenable to future supramolecular applications. A thorough analysis of the voltammetry indicates a 107 decrease in Kdim upon oxidation. This result coupled with the high stability of the oxidized form suggests UPy(Fc) is highly amenable to supramolecular applications. Currently we are working on the synthesis of linked UPy(Fc)’s suitable for the formation of supramolecular polymers. Progress on this work will be reported. Figure 1

Proton transfer often accompanies electron transfer in organic redox couples due to the large changes in acidity or basicity that result from oxidation or reduction. Classically, the overall reaction is thought to occur in two separate steps, either proton transfer followed by electron transfer, PT-ET, or electron transfer followed by proton transfer, ET-PT. More recently it has become abundantly apparent that a third option is also possible in which the proton and electron move together in a single kinetic step. This is concerted proton-electron transfer, CPET, and is generally believed to occur within a H-bonded intermediate. It is straightforward to show that E° of this step will have a value in between the E° values corresponding to the oxidation of the fully protonated and fully deprotonated forms. Experimental evidence for CPET is typically the observance of a significant deuterium isotope effect for the apparent one electron transfer. However, it is important to note that the electron-proton transfer does not have to be concerted within the H-bond complex. It could also occur step-wise. If slow electron transfer occurred followed by rapid proton transfer within the H-bond complex, no significant deuterium isotope effect would be expected, yet, at the same time, the overall reversibility of the electron-proton transfer would still be aided by providing a mechanistic pathway through the H-bond complex with its intermediate E°. We believe that the second oxidation of a simple phenylenediamine, H2PD, in the presence of pyridines in acetonitrile provides a nice example of the significant role that step-wise electron-proton transfer within a H-bond intermediate can play. Without added base, the second oxidation corresponds to the reversible one electron oxidation of the radical cation, H2PD+, to the quinoidal dication, H2PD2+. CV data in the presence of one equivalent of pyridines of different basicity result in a significant negative shift in the E1/2 of the second CV wave with no loss in reversibility. Continued addition of the pyridine leads to smaller incremental shifts with still no change in reversibility. Analysis of the observed E1/2’s with one equivalent pyridine as a function of pyridine basicity indicates that, even with the weakest base, proton transfer to the pyridine occurs. This interpretation is supported by spectroelectrochemical data. Thus, the overall reaction occurring in the second CV wave is H2PD+ + B = HPD+ + HB+ + e-, where B is the pyridine base and HB+ is its conjugate acid. The shifts in E1/2 upon further additions of pyridine are nicely predicted by the Nernst equation with this as the overall reaction. However, attempts to simulate the CV data with just PT and ET steps fail at the higher concentrations of pyridine. This is because the rate of the ET step becomes exceedingly slow as the base concentration increases and the thermodynamic potential becomes increasingly removed from the E° of the actual ET step. This issue is simply solved by including in the mechanism the possibility of electron transfer occurring through the H-bond intermediate. This simple change leads to good fits to the experimental data, providing solid support for such a H-bonding intermediate being involved. However, a comparison of experiments with 10:1 cyanopyridine: H2PD run in 2% CH3OH to those run in 2% CD3OD show no significant difference in the ΔEp of the second oxidation, providing no evidence for the oxidation involving CPET. Thus, it appears that ET-PT within the H-bond complex still greatly aids the reversibility of the reaction even without CPET.

Ureidopyrimidones (UPy's) are well-known to dimerize via 4 strong H-bonds in noncompetitive solvents. Although UPy dimers have been widely studied, there are few examples of UPy's containing redox-active groups, and even fewer in which oxidation/reduction has been shown to affect dimerization. In this study, a thorough electrochemical investigation of a UPy with a ferrocene attached to the 6-position of the pyrimidone ring, UPy(Fc), demonstrates that strong and reversible redox-control of dimerization is possible in the UPy system. 1H NMR shows that the reduced UPy(Fc) is fully dimerized under electrochemical conditions in CH2Cl2. Cyclic voltammetry (CV) shows that oxidation of the ferrocene to the ferrocenium converts the dimer to another species with a less positive E1/2, and that reduction of this species reforms the dimer in a chemically reversible fashion. Analysis of the scan rate and concentration dependence of the CV's along with the relative diffusion coefficient measurements strongly suggest that the oxidized form is the monomer. Simulation of the CV data gives a Kdis of 2.1 × 10-6 M in the reduced state and 12 M in the oxidized state. This large redox dependence is likely due to oxidation creating both electrostatic repulsion between monomers and greatly decreasing the H-accepting ability of the pyrimidone.

At one extreme, supramolecular polymers can have a high degree of randomness, existing as entangled coils with the mechanical properties of plastics and elastomers. At the other extreme, supramolecular polymers can be formed through directional intermolecular interactions among designed molecular subunits to achieve dynamic behavior as well as high degrees of internal order. The strength of these intermolecular interactions can be altered via external signals such as the absorption of light, temperature, pH, or the voltage of an electrode. Such is one of the important goals in supramolecular chemistry: the development of stimuli-responsive systems where the strength of intermolecular interactions can be perturbed through the use of external signals. Applications of supramolecular chemistry include self-healing polymers and gels, controlled release of entrapped molecules, and smart materials. In this presentation the results of electrochemical studies with a ferrocene-containing ureidopyrimidone (UPy) will be described. The UPy system – introduced by Meijer – can form two self-complementary 4 hydrogen bond arrays (AADD or ADAD) which dimerize in relatively non-polar organic solvents. By attaching an electroactive substituent such as ferrocene, the strength of electrostatic interactions can be perturbed to create a redox-responsive ureidopyrimidinone. Following earlier studies by Graham and co-workers, a ferrocene-functionalized ureidopyrimidinone UPy(Fc) was prepared. Concentration and scan-rate-dependent cyclic voltammetric studies indicate a square scheme type mechanism in dichloromethane. In the starting UPy(Fc) state, the AADD dimer is preferred. Oxidation to UPy(Fc+) results in conversion to another form with a less positive E1/2. Preference for this new form increases at lower concentrations which suggests that UPy(Fc+) exists as a monomeric species. This would indicate that oxidation breaks the dimer apart as desired. Alternatively it is possible that the observed concentration dependence results from rate-limiting dissociation of the dimer, but the monomer then tautomerizes to the ADAD enol form and re-dimerizes. To distinguish between these possibilities the relative diffusion coefficients (D’s) of UPy(Fc+) to UPy(Fc) were measured by steady-state voltammetry at a microdisk electrode. They were then compared to the relative D’s of ferrocenium to ferrocene. If UPy(Fc) is a dimer in both oxidation states, the DUPy(Fc+)/DUPy(Fc) ratio should be similar to that observed for ferrocene (DFc+/DFc), which will be a monomer in both oxidation states. However, if UPy(Fc+) is a monomer, the DUPy(Fc+)/DUPy(Fc) ratio will be larger than DFc+/DFc, since the D of the UPy(Fc+) monomer will be relatively smaller than the D of the UPy(Fc) dimer due to its smaller size. The latter is observed, supporting the conclusion that oxidation breaks apart the UPy(Fc) dimer at mM concentrations in dichloromethane. The results of these studies support the conclusion that UPy(Fc+) is monomeric at milli-molar concentrations in dichloromethane, meaning that oxidation of the UPy(Fc) breaks apart the dimer as hypothesized. Furthermore the process appears to be completely reversible. CV simulations were performed to determine if the square mechanism can quantitatively explain the observed voltammetry. The resulting simulated CV data supported the use of a square scheme mechanism to explain the cyclic voltammetry. However, the mechanism only accounts for the predominant keto AADD tautomer and excludes the enol ADAD tautomer. HNMR studies mimicking experimental conditions in cyclic voltammetry have been performed, revealing the presence of the enol ADAD tautomer in dichloromethane. Further HNMR studies in dichloromethane are underway, along with a comparative study in chloroform which does not appear to contain the enol ADAD tautomer. Cyclic voltammetry of the Upy(Fc) system will also be performed in chloroform. The results of these experiments will determine if the enol ADAD contributes to the redox mechanism of UPy(Fc). In addition, the synthesis of covalently linked UPy(Fc) oligomers is being initiated with the goal of creating a redox-responsive supramolecular polymer.

Supramolecular polymers can be formed through directional intermolecular interactions between designated molecular subunits in order to achieve dynamic behavior. The strength of these intermolecular interactions can be altered through the use of external signals such as light absorption, changes in temperature and/or pH, or in an almost unexplored caveat, the application of voltage. Such is one of the important goals in supramolecular chemistry: the development of stimuli-responsive systems where the strength of intermolecular interactions can be perturbed through the use of external signals. Applications of supramolecular chemistry include self-healing polymers and gels, controlled release of entrapped molecules, and the development of smart materials. Ureidopyrimidinones (UPy) – introduced by Meijer and coworkers – can form two self-complementary 4 hydrogen bond arrays with binding motifs AADD or ADAD and have a relatively small dissociation constant of 10-6. Due to their directionality and strength of dimerization, UPys have been widely imployed as polymer cross-linkers in oligomerization and also as capping agents in chain termination. In these cases, association and/or dissociation of UPy hydrogen bonded complexes are influenced by external signals that were previously described. However, the application of voltage to affect binding of the UPy supramolecular complex is a relatively new approach towards dimerization control. In order for UPy to show electrochemical responsiveness, an electroactive substituent needs to be attached to the UPy framework. We have prepared and characterized such a system in which a ferrocene (Fc) is attached to the pyrimidone ring in the UPy. Concentration and scan-rate-dependent cyclic voltammetry and diffusion coefficient data from bulk electrolysis coupled with steady-state voltammetry indicate a square scheme mechanism for the UPyFc / UPyFc+ redox couple in dichloromethane. The fully reduced UPyFc exists as a dimer. Upon oxidation to UPyFc+, the dimer breaks apart to form the monomer. However, it is unknown how conversion between the AADD and ADAD binding motifs – due to tautomerization – factors into the square scheme mechanism. Nonetheless CV simulations with a simple square scheme mechanism (neglecting tautomerization) provide reasonable fits to the experimental data. Importantly, the overall process appears to be completely chemically reversible even over the relatively long time scale of bulk electrolysis. Based off of this preliminary work, syntheses of covalently-linked UPyFc oligomers are underway with the goal of creating a redox-responsive supramolecular polymer whose physical properties can be altered upon oxidation. As it has been confirmed that the fully reduced UPyFc exists as a dimer, the physical properties of the material should reflect this dimerization by showing rigidity or in some cases, a highly viscous material. Upon oxidation, dimerization should cease, causing the ferrocene-UPy oligomer to break apart and show physical properties that reflect a loss in rigidness and greater fluid, thereby achieving a more selective process of perturbing electrostatic interactions in supramolecular assemblies.