H-bonding Motifs Research Articles

Halogen-bonded building block for 2D self-assembly: Triggered by hydrogen-bonding motifs relative to the terminal functions of the side chains

Owning to the excellent applications of halogen bonds in supramolecular chemistry, the recognition of halogen bonds is of significance during molecular self-assembly process. The 2D self-assembly of fluorenone molecules (BEDF, BCDF, and BHDF) characterized by different terminal groups have been studied at the 1-phenyloctane/HOPG interface. The H-bonding motifs relative to the terminal groups determine the bonding motifs of the conjugated cores and serve as the trigger of halogen bonds. The COOC2H5-terminated groups of BEDF sever as hydrogen bond acceptors to bond with the cores, giving rise to the dimer configuration of cores linked by CH···Br hydrogen bonds. By contrast, the COOH-terminated groups of BCDF and the OH-terminated groups of BHDF act as both the electrophile and nucleophile interacted with the cores. On account of the secondary hydrogen bond distinct in strength and the different intersection of the aggregates, the type-I bonds (Br···Br) and halogen bonds (Br···OC and Br···Br) are observed in the networks of BCDF and BHDF, respectively. The types of halogen bonds could be further modified by changing the concentrations. The work clearly demonstrates that an appreciation of terminal functions is critical to the recognition of halogen bonds, thus establishing the controllable self-assembly morphology.

X-ray Structure at 150 K of the Polar Alkyl Mesogenic Compound 7CBB: 4-Cyanobiphenyl-4′-heptylbiphenyl Carboxylate

The compound under study 7CBB consists of two biphenyl moieties A–B and C–D linked by a carboxylate group. Ring A terminates in a 4-cyano group and C–D is linked to the terminal alkyl chain. A previously reported room temperature determination of the crystal structure employing MoKα X-radiation was thought to contain serious errors in describing the alkyl chain as being disordered. The X-ray structure factors were not deposited with this published structure and as a consequence two new X-ray data sets have been collected: (1) using MoKα radiation at room temperature 295 K (a repeat of the previous study) and (2) using CuKα radiation at 150 K in an attempt, which proved successful, to improve the overall quality of the structure determination. The corrected MoKα structure and the CuKα structure both reported here have enabled the previous errors to be identified, concluding that there is no disorder in the alkyl chain. The alkyl chain in the MoKα structure at 295 K was found to have anisotropic thermal factors slightly exaggerated with respect to the remainder of the structure. However, this effect is not observed in the CuKα structure at 150 K, all anisotropic thermal factors including those in the alkyl chain being reduced to cover a much smaller overall range of values. Consequently, it can be concluded that the effect observed in the alkyl chain at 295 K is merely one of a thermal nature, not one of disorder. There are no unusual bond lengths or angles present. The biphenyl moieties are planar within 0.035 A and 0.020 A respectively. The dihedral angles of all ring pairs have been calculated. Calculation of intermolecular distances between molecules related by a centre of symmetry reveals the existence of a number of van-der Waals interactions. The H-bonding motif typical of crystal structures of cyanobiphenyl compounds is observed. The molecular packing mode corresponds to that of a precursor of the smectic phase. The alkyl chain thermal ellipsoids for 7CBB (a) the Mo RT structure are noticeably exaggerated compared to those for the remainder of the structure, an effect which is not present in (b) the Cu LT structure (Drawn with Ortep/Raster (Barnes in J Appl Cryst 30:568, 1997; Merritt and Bacon in Methods Enzymol 277:505–524, 1997)). It may be concluded therefore that in the Mo RT structure this is a thermal effect and cannot be explained in terms of static disorder.

Thermoresponsivity, Micelle Structure, and Thermal-Induced Structural Transition of an Amphiphilic Block Copolymer Tuned by Terminal Multiple H-Bonding Units.

Constructing noncovalent interactions has been a benign method to tune the stimuli responsivity and assembled structure of polymers in solution; this is essential for controlling the functions and properties of stimuli-responsive materials. Herein, we demonstrate a novel supramolecular strategy to manipulate the cloud point (Tcp) and assembled structure of thermoresponsive polymers in solution by using H-bonding interactions. We use poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b- poly(lactide-co-glycolide) (PLGA-PEG-PLGA) as a model thermoresponsive polymer and functionalize its chain terminals by the self-complementary quadruple H-bonding motif, 2-ureido-4[1H]-pyrimidinone (UPy). UPy end functionalization and increasing PLGA block length decrease the Tcp of copolymer. Both UPy- and nonfunctionalized copolymers form the spherical micelles at low temperature. They undergo the intermicellar aggregation and form large compound micelles during heating; this thermally induced structural transition causes the presence of Tcp. Due to the UPy-UPy H-bonding interactions, UPy end functionalization leads to more copolymer chains to associate in one micelle, thus, enhancing the hydrodynamic, gyration radii, core size, as well as the packing density of PLGA in micelle core and grafting density of PEG on core-shell interface. The decreased Tcp of UPy-functionalized copolymer stemmed from the stronger intermicellar attractions at high temperature. Furthermore, UPy-functionalized copolymers exhibit higher drug loading content, slower drug release rate, and better separation efficiency in removing the hydrophobic substances from water than PLGA-PEG-PLGA precursors.

Metallo-responsive self-assembly of lipophilic guanines in hydrocarbon solvents: a systematic SAXS structural characterization.

Lipophilic guanines (LipoGs) in aprotic solvents undergo different self-assembly processes based on different H-bonded motifs. Cylindrical nanotubes made by π-π stacked guanine tetramers (G-quadruplexes) and flat, tape-like aggregates (G-ribbons) have been observed depending on the presence of alkali metal ions. To obtain information on the structural properties and stability of these LipoG aggregates, Small-Angle X-ray Scattering (SAXS) experiments have been performed in dodecane, both in the presence and in the absence of potassium ions. As a result, the occurrence of the two different metallo-responsive architectures (nanoribbons or columnar nanotubes) was confirmed and we reported here for the first time a systematic study on the dependence of the aggregate properties on composition, temperature and molecular unit structure. Even if dodecane was selected to favour LipoG solubility, a strong tendency to self-organize into ordered lyotropic phases was indeed detected.

An intraresidue H-bonding motif in selenocysteine and cysteine, revealed by gas phase laser spectroscopy and quantum chemistry calculations.

Models of protein chains containing a seleno-cysteine (Sec) residue have been investigated by gas phase laser spectroscopy in order to document the effect of the H-bonding properties of the SeH group in the folding of the Sec side chain, by comparison with recent data on Ser- and Cys-containing sequences. Experimental data, complemented by quantum chemistry calculations and natural bonding orbital (NBO) analyses, are interpreted in terms of the formation of a so-called 5γ intra-residue motif, which bridges the acceptor chalcogen atom of the side chain to the NH bond of the same residue. This local structure, in which the O/S/Se atom is close to the plane of the N-terminal side amide, is constrained by local backbone-side chain hyperconjugation effects involving the S and Se atoms. Theoretical investigations of the Cys/Sec side chain show that (i) this 5γ motif is an intrinsic feature of these residues, (ii) the corresponding H-bond is strongly non-linear and intrinsically weak, (iii) but enhanced by γ- and β-turn secondary structures, which promote a more favorable 5γ H-bonding approach and distance. The resulting H-bonds are slightly stronger in selenocysteine than in cysteine, but nearly inexistent in serine, whose side chain in contrast behaves as a H-bonding donor. The modest spectral shifts of the Cys/Sec NH stretches measured experimentally reflect the moderate strength of the 5γ H-bonding, in agreement with the correlation obtained with a NBO-based H-bond strength indicator. The evolution along the Ser, Cys and Sec series emphasizes the compromise between the several factors that control the H-bonding in a hyperconjugation-constrained geometry, among them the chalcogen van der Waals and covalent radii. It also illustrates the 5γ H-bond enhancements with the Sec and Cys residues favoured by the constraints imposed by the γ- and β-turn structures of the peptide chain.

7-Azaindole-3-carboxylic acid and its Pt(II) and Pd(II) complexes: Crystal structure of the ligand, vibrational spectra, DFT calculations and in vitro antiproliferative activity

The crystal and molecular structure of 7-azaindole-3-carboxylic acid (7AI3CAH2) has been determined by a single-crystal X-ray diffraction analysis (space group Pca21, a = 14.247(3), b = 5.1983(10), c = 9.871(2) Å, V = 731.0(2) Å3, Z = 4). The crystal structure consists of chains of the 7AI3CAH2 molecules, arranged into ribbons and connected via intermolecular O–H⋯N and N–H⋯O hydrogen bonds. The IR and Raman spectra of 7AI3CAH2 and its deuterated derivative were recorded in the solid state. The DFT calculations at the B3LYP/6–311++G(d,p) level were performed for four conformers of the 7AI3CAH2 monomer as well as for the dimer and trimer, which included intermolecular H-bonding motifs. The analogous calculations were carried out for the deuterated derivative (7AI3CAD2). The optimized structural parameters and the calculated vibrational spectra of trimer reproduce the experiment very well. In addition, new complexes of 7AI3CAH2 with Pt(II) and Pd(II) were prepared and studied by infrared and Raman spectroscopy. The geometry optimizations and vibrational frequency calculations were conducted for two possible (cis and trans) isomers of [MCl2(7AI3CAH2)2] (where M = Pt(II) or Pd(II)) using the B3LYP method with the 6–311++G(d,p)/LanL2DZ basis sets. The combined experimental and theoretical vibrational spectroscopic studies have shown that in the solid state the platinum(II) complex exists as the cis isomer (cis-[PtCl2(7AI3CAH2)2]), whereas the palladium(II) complex has the trans conformation (trans-[PdCl2(7AI3CAH2)2]). In both isomers, two pyridine nitrogen atoms of the 7AI3CAH2 ligands and two chloride ligands are coordinated to the central Pt(II) or Pd(II) atoms in a square-planar arrangement. The carboxylic and NH groups of 7AI3CAH2 are not bonded by metal ions. Detailed vibrational assignments for 7AI3CAH2 and its Pt(II) and Pd(II) complexes have been made on the basis of the calculated potential energy distributions (PEDs). The in vitro antiproliferative activities of cis-[PtCl2(7AI3CAH2)2] and trans-[PdCl2(7AI3CAH2)2] were studied on two human cancer cell lines (T47D and A549). As follows from the obtained IC50 values, the trans-[PdCl2(7AI3CAH2)2] complex exhibits cytotoxicity against T47D cell line, which is comparable to that of cisplatin.

Integrating transient and sacrificial bonds into biobased elastomers toward mechanical property enhancement and macroscopically responsive property

The development of biobased polymers from renewable resources offers a solution to the growing environmental concerns and scarcity of fossil feedstock. The synthesized biobased polymers, especially for biobased elastomers, are mechanically weak, which greatly restricts their applications. In the present work, we demonstrate that the integration of transient and sacrificial quadruple H-bonding motifs into as-synthesized biobased elastomer can enhance the mechanical properties and bestow it with adaptive performance. Specially, the biobased elastomer was synthesized through melting poly-condensation using biobased di-acids and diols as the starting materials. The biobased elastomer is covalently crosslinked and grafted with ureido-pyrimidinone (UPy) containing acrylate through thiol-ene click reaction by using pentaerythritol tetra(3-mercaptopropionate) as the linkers. Under external load, UPy aggregations based on H-bonding can function as sacrificial units through reversible rupture and re-formation events, leading to significant improvements on the modulus and strength of the biobased elastomer while maintaining the extensibility. In addition, the dissociation and re-formation of H-bonding under thermal stimuli impart the elastomer with thermo-activated shape memory behavior.

IrIII as a strategy for preorganisation in H-bonded motifs

ABSTRACT We report how four sets of thiourea-based heterodimers interact, and how incorporation of a metal centre imparts reduced degrees of rotational freedom. Through single-crystal X-ray diffraction, 1H NMR, and UV-vis analysis, the interactions of these systems are dissected and presented. These motifs are considered to be stable and desirable for supramolecular hydrogen-bonded functional materials. Interpretation of the structural design of thiourea-based ligand and its incorporation into metal complexes can contribute to the understanding of preorganised self-assembly and open new pathways in design of novel soft materials. This work also contributes to the unexplored library of hydrogen-bonded metal complexes based on iridium. As such we examined the photoluminescence of the system of general formula [Ir(C^N)2(N^S)] and the effect of hydrogen bonding on the emission properties when combined with different n-heteroacenes.

Morphology and thermodynamics of polymers with monofunctional hydrogen bonding ends in dilute and semidilute concentration.

Rheological properties of supramolecular polymers (SMPs) depend on their equilibrium structure including the size, the number, and the topology of aggregates. A polymer with a hydrogen bonding (H-bonding) motif at both ends is one widely used precursor to build SMPs. Due to the complex interplay between chain stiffness, H-bonding interaction, polarity along a chain, and polymer conformational entropy, it is difficult to theoretically predict the structure of SMPs. In this work we investigate thermodynamics of SMPs with H-bonding ends in a wide range of densities. A replica exchange stochastic approximation Monte Carlo method with coarse-grained models for polyethylene and polybuthylene glycols is used. Our simulation shows that SMPs have two morphological transition lines with increasing temperature, a ring-linear transition, and a linear-free chain transition. The latter is a thermodynamic transition and turns out to be continuous. Comparing the two different spacers, we find that ring-linear transition temperatures differ from each other at the constant volume fraction due to different looping probabilities, which can be calculated from the average polymer size by mean field. However, the linear-free chain transition temperatures are similar because the entropic penalty to form a hydrogen bond mainly depends on the probability of finding H-bonding groups in a system, which is the same for both systems at a given volume fraction.

Synthesis and XRD study of an C2-linked bis(quaternary ammonium) pentaborate: [Me3NCH2CH2NMe3][B5O6(OH)4

The synthesis and characterization of a C2 (ethane) linked bis(trimethylammonium) pentaborate salt, [Me3NCH2CH2NMe3][B5O6(OH)4]2 (1), is reported . Compound 1 has been characterized by 1H, 11B, and 13C NMR Spectroscopy, IR spectroscopy, thermal (TGA/DSC) analysis, and single-crystal X-ray diffraction. There are two independent crystallographic pentaborate(1-) anions in the solid-state structure and these link by H-bonds at β-sites into a centrosymmetric tetrameric chain. These chains are crossed-linked by R22(8) H-bond motifs to α-sites of neighboring pentaborate tetrameric units. The [Me3NCH2CH2NMe3]2+ cations are located between these tetrameric pentaborate(1-) units.

High-Performance Polymeric Materials through Hydrogen-Bond Cross-Linking.

It has always been critical to develop high-performance polymeric materials with exceptional mechanical strength and toughness, thermal stability, and even healable properties for meeting performance requirements in industry. Conventional chemical cross-linking leads to enhanced mechanical strength and thermostability at the expense of extensibility due to mutually exclusive mechanisms. Such major challenges have recently been addressed by using noncovalent cross-linking of reversible multiple hydrogen-bonds (H-bonds) that widely exist in biological materials, such as silk and muscle. Recent decades have witnessed the development of many tailor-made high-performance H-bond cross-linked polymeric materials. Here, recent advances in H-bond cross-linking strategies are reviewed for creating high-performance polymeric materials. H-bond cross-linking of polymers can be realized via i) self-association of interchain multiple H-bonding interactions or specific H-bond cross-linking motifs, such as 2-ureido-4-pyrimidone units with self-complementary quadruple H-bonds and ii) addition of external cross-linkers, including small molecules, nanoparticles, and polymer aggregates. The resultant cross-linked polymers normally exhibit tunable high strength, large extensibility, improved thermostability, and healable capability. Such performance portfolios enable these advanced polymers to find many significant cutting-edge applications. Major challenges facing existing H-bond cross-linking strategies are discussed, and some promising approaches for designing H-bond cross-linked polymeric materials in the future are also proposed.

Use of a Redox-Responsive 4 H-Bond Ureidopyrimidone (UPy) Array to Control Polymerization in a Upy-Based Supramolecular Polymer

Ureidopyrimidinone (UPy) derivatives, introduced by Meijer and co-workers, are capable of forming dimers linked by four strong H-bonds. They have been widely used as polymer crosslinkers in self-healing supramolecular polymers and gels. While their donor-donor-acceptor-acceptor (DDAA) H-bond motif contributes to polymer stretchiness, their relatively high association constant of 106 also contributes to their ability to autonomously self-repair. This presentation shows the result of substituting a UPy with a N,N- dimethyl-p-phenylenediamine and therefore adding a redox reactive dimension to self-repair. In particular, this work involves the electrochemical investigation of UPyH (shown below) with a series of different bases, specifically pyridine and substituted pyridines. The focus is on finding the appropriate electroinactive base that facilitates both the dimer break up upon oxidation and proton transfer and dimer reformation by reduction and back proton transfer. Cyclic voltammetry (CV) scans of UPyH only, conducted in CH2Cl2 at slower scan rates, show two reversible redox waves. The first wave is of one electron height, corresponding to a two-electron transfer per dimer. At a higher oxidation potential, the second oxidation wave is one half the height of the first and then on the return scan, a slightly more negative potential is needed for reduction. At a faster scan rate, the CV response for the second wave shows that it becomes irreversible. Also, at a faster scan rate, a new reduction wave appears at a more negative peak potential than the reduction wave for the first electron transfer process. This type of CV return wave behavior for UPyH at faster scan rates was previously seen in another dimethylphenylurea redox active compound with only two H-bonding sites, UHH. In the UHH investigation, CV and spectroelectrochemical results pointed to the dimethylamino moiety being basic enough to abstract an N-H proton in the radical cation oxidation state and therefore allowing for a two electron transfer wave to give the quinoidal cation. A similar reduction wave negative of the first redox wave was seen in acetonitrile at all scan rates, while in CH2Cl2 this wave was seen only at faster scan rates. At slower scans the first oxidation remained reversible. Based upon the UHH study, interpretation of the UPyH second oxidation wave is that it correspond with a second e- transfer per redox center. Each urea-phenylenediamine N-H site in the dimer then becomes acidic enough to transfer its proton to the carbonyl oxygen on the UPyH isocytosine. This would then change the favorable binding motif of DDAA to a weaker binding motif of ADAD. In addition, a 2+ charge forms on each monomer in the dimer contributing to strong repulsive forces. This results in dimer break-up, where upon the protonated isocytosine carbonyl on each monomer is exposed to the more basic dimethylamino site on a fully reduced UPyH dimer. Proton transfer from the isocytosine to the dimethyl amino renders the fully reduced dimer electroinactive, explaining the half wave height. Thus, the overall reaction, shown in the accompanying scheme, corresponds to break up of the half the starting dimers, with two electron oxidation and deprotonation of each monomer to give two UPy+. However, the other half of the UPy’s remain dimerized in the protonated form as (HUPyH+)2. Further investigation focuses on the addition of a series of substituted pyridines as a base and their effect on dimer break up and reformation as it competes with the dimethylamino moiety on the phenylenediamine. The goal is to find an external base that will allow full oxidation and break up of all the UPyH dimers, while retaining the chemical reversibility of the process. UPy has a unique self-healing property that can be observed electrochemically as a redox couple which can be useful for supramolecular polymers. With the use of UPyH’s H-bond array and a phenylenediamine redox couple attached to the urea, this would allow H-donating of the NH urea. The main focus of this study is UPyH+ base will be used as a redox-controlled chain terminator that can control the degree of polymerization. The viscosity of the supramolecular polymers will determine if UPyH base would act as a chain terminator, and if it would be electroactive to oxidize to deactivate the polymer chain to reform a chain with the base. When the polymers reduce, UPyH would go back at its starting state by reforming with itself.

Radical Rebound Hydroxylation Versus H-Atom Transfer in Non-Heme Iron(III)-Hydroxo Complexes: Reactivity and Structural Differentiation.

The characterization of high-valent iron centers in enzymes has been aided by synthetic model systems that mimic their reactivity or structural and spectral features. For example, the cleavage of dioxygen often produces an iron(IV)-oxo that has been characterized in a number of enzymatic and synthetic systems. In non-heme 2-oxogluterate dependent (iron-2OG) enzymes, the ferryl species abstracts an H-atom from bound substrate to produce the proposed iron(III)-hydroxo and caged substrate radical. Most iron-2OG enzymes perform a radical rebound hydroxylation at the site of the H-atom abstraction (HAA); however, recent reports have shown that certain substrates can be desaturated through the loss of a second H atom at a site adjacent to a heteroatom (N or O) for most native desaturase substrates. One proposed mechanism for the removal of the second H-atom involves a polar-cleavage mechanism (electron transfer-proton transfer) by the iron(III)-hydroxo, as opposed to a second HAA. Herein we report the synthesis and characterization of a series of iron complexes with hydrogen bonding interactions between bound aquo or hydroxo ligands and the secondary coordination spherein ferrous and ferric complexes. Interconversion among the iron species is accomplished by stepwise proton or electron addition or subtraction, as well as H-atom transfer (HAT). The calculated bond dissociation free energies (BDFEs) of two ferric hydroxo complexes, differentiated by theirnoncovalent interactions and reactivity, suggest that neither complex is capable of activating even weak C-H bonds, lending further support to the proposed mechanism for desaturation in iron-2OG desaturase enzymes. Additionally, the ferric hydroxo species are differentiated by their reactivity toward performing a radical rebound hydroxylation of triphenylmethylradical. Our findings should encourage further study of the desaturase systems that may contain unique H-bonding motifs proximal to the active site that help bias substrate desaturation over hydroxylation.

Twelve-coordinated sulfate hydrogen bonding interactions in water-containing Fe(II) system

Twelve-coordinated sulfate hydrogen bonding interactions in water-containing Fe(II) system, [Fe0.5(H2O)3]2SO4·H2O (1), are reported herein. The X-ray single-crystal structural characterization suggests that the SO42− anion is coordinated by a total of twelve O–H···O hydrogen bonds from coordinated or free water molecules, with each sulfate O atom accepting three H-bonds in water-containing Fe(II) system. A well-defined cyclic (10) H-bonding motif is found in the sulfate − water clusters, which is extended into 2D sulfate − water H-bonding sheet. An 1D infinite [SO42−−H2O]n chain is further cross-linked with the 2D H-bonding sheet above mentioned to form a 3D sulfate − water hydrogen bonding network stabilized by the O–H···O hydrogen bonds interactions. The sulfate saturated coordination of 12 hydrogen bonds from water molecules in its first hydration shell is confirmed by X-ray crystallography.

Influence of aromatic nitro-substituents on auto-reusability of oxime-based fluoride receptors

Abstract The interaction of fluoride ion with three oxime based receptors containing additional aromatic nitro-substituents was studied by using colorimetric and NMR spectroscopy. Colorimetric responses of the receptors towards fluoride ion were found to be highly dependent on the position of the nitro substituent in the aromatic backbone. While the ortho and para nitro-substituted receptors showed intense colour change and associated colorimetric response upon addition of fluoride, the meta derivative did not provide any visible deviation in colour as well as colorimetric behaviour. Further, due to the presence of H-bond acceptor motif, the receptor–fluoride complexes formed by both ortho and para nitro-substituted derivatives are reasonably labile and dissociate to automatically result in the free receptor species within a short time span. This allowed reuse of the receptor solution for selective and successive recognition of fluoride by colorimetric technique without any external trigger.Graphical Abstract Three new oximes with additional aromatic nitro-substituents are prepared and their interaction of fluoride ion was studied. The position of nitro-substituents profoundly influences the ability to reuse the receptors for colorimetric recognition of fluoride. Based on spectroscopic studies, a possible mechanism for auto-regeneration of the fluoride free receptors is detailed.

Use of a Redox-Responsive 4 H-Bond Ureidopyrimidone (UPy) Array to Control Polymerization in a Upy-Based Supramolecular Polymer

Ureidopyrimidinone (UPy) derivatives, introduced by Meijer and co-workers, are capable of forming dimers linked by four strong H-bonds. They have been widely used as reversible crosslinkers in self-healing supramolecular polymers and gels. The goal of the project to be presented is to create a redox-controllable UPy supramolecular polymer system by adding a redox-responsive UPy monomer as a capping agent to a solution of a non-redox-active UPy supramolecular polymer. Specifically, a UPy containing a phenylenediamine redox couple, UPyH, that we have previously studied,1 will be used as the capping agent. In previous work we have shown that UPyH dimerizes in methylene chloride with Kdim > 105 as expected. Oxidation of the phenylenediamine to the radical cation does not break apart the dimer at mM concentrations. However, further oxidation to the quinoidal dication weakens the binding enough to allow an external base to remove the most acidic protons and thereby create a non-self-complementary H-bonding motif that cannot dimerize. As long as the base is not too strong the process is reversible on the cyclic voltammetric time scale, leading to re-formation of the UPyH dimer upon reduction. Previous studies show that 1 equivalent of 4-trifluoromethylpyridine is a good choice for the base. To create the redox-responsive supramolecular polymer system, a known UPy oligomer will be used to prepare a supramolecular polymer solution in methylene chloride electrolyte solution. The degree of polymerization will be assessed by measuring the viscosity of the solution. UPyH plus an equal amount of 4-trifluoromethylpyridine will be then added until there is a significant decrease in viscosity indicating that the UPyH is H-bonding to the UPy’s in the non-redox active UPy oligomer and thereby decreasing the length of the supramolecular chains. The solution will then be oxidized either chemically or electrochemically to convert the UPyH to its fully oxidized, de-protonated form. Since this form is incapable of dimerizing with itself or another UPy, the UPyH will lose its viability as a chain terminator, thus allowing the non-redox active Upy oligomers to reform supramolecular chains. This will be signaled by an increase in the viscosity of the solution. 1L. A. Clare and D. K. Smith, Chemical Communications 2016, 52, 7253-7256.

Redox-Dependent H-Bonding with Electroactive Ureas: The Effect of One Electron Vs. Two Electron Redox Couples

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

Insight into the Role of Hydrogen Bonding in the Molecular Self-Assembly Process of Sulfamethazine Solvates

The new solid forms screening of sulfamethazine was conducted in 16 kinds of different pure solvents. Four new sulfamethazine solvates were reported for the first time, and three crystal structures of solvates were successfully determined from single-crystal X-ray diffraction data. The results showed that sulfamethazine solvate formation directly depended on the solvents used in the experiments. The solvent properties were used to evaluate the effects of solvent on solvate formation. It was found that the H-bond acceptor ability of the solvent was the main factor that governed the solvate formation. The H-bonded motifs in the structures of solvates have been fully characterized. The results revealed that sulfamethazine solvate formation was mainly driven by molecular self-assembly through hydrogen bonding between solvent and solute molecules. Meanwhile, the crystal structures results also showed that the sulfamethazine molecule had flexible conformation. Furthermore, the principles of different sulfamethazine molecules packing in different crystal structures were discussed from the view of molecular intermolecular interactions and the molecular conformation.

Characterization of Doubly Ionic Hydrogen Bonds in Protic Ionic Liquids by NMR Deuteron Quadrupole Coupling Constants: Differences to H-bonds in Amides, Peptides, and Proteins.

We present the first deuteron quadrupole coupling constants (DQCCs) for selected protic ionic liquids (PILs) measured by solid-state NMR spectroscopy. The experimental data are supported by dispersion-corrected density functional theory (DFT-D3) calculations and molecular dynamics (MD) simulations. The DQCCs of the N-D bond in the triethylammonium cations are the lowest reported for deuterons in PILs, indicating strong hydrogen bonds between ions. The NMR coupling parameters are compared to those in amides, peptides, and proteins. The DQCCs show characteristic behavior with increasing interaction strength of the counterion and variation of the H-bond motifs. We report the similar presence of the quadrupolar splitting pattern and the narrow liquid line in the NMR spectra over large temperature ranges, indicating the heterogeneous nature of PILs.

The Effect of Proton Transfer on Redox-Responsive Dimerization in Electroactive 4 H-Bond Arrays

The design of stimuli-responsive systems is an important topic in supramolecular chemistry. These are systems in which an external signal, such as a change in light, temperature, pH or voltage on an electrode, results in structural changes in the supramolecular assembly. Applications include self-healing polymers and gels, controlled release of entrapped molecules and smart materials. Over the years our group has investigated a number of simple systems in which electron transfer is used to perturb the strength of H-bonding interactions. More recently we have expanded the research to include larger H-bond arrays. In particular we have been investigating several different electroactive ureidopyrimidones or UPy’s, which are capable of strong self-dimerization through the formation of 4 linear H-bonds. Non-electroactive UPy’s have already been widely used in the construction of supramolecular polymers and gels capable of self-repair; introduction of electroactive UPy’s in which dimerization can be controlled electrochemically will make even more types of applications possible. These systems are also of interest from a fundamental standpoint in that they provide a well-understood platform in which to investigate the role of intermolecular H-bonding (and proton transfer) on electron transfer.The principle behind redox-responsive H-bonding is straightforward: an oxidation that decreases the negative charge on a H-acceptor (A) or reduction that decreases the positive charge on a H-donor (D) will weaken a H-bond. Alternatively, reduction that increases the negative charge on a H-acceptor or oxidation that increases the positive charge on a H-donor will increase the strength of a H-bond. However, in the latter case, it is possible that oxidation or reduction could also lead to full proton transfer. If this occurs across the H-bond, the primary H-bonds will stay the same, but the secondary H-bonds will change, possibly in a way that has an undesired effect. It is also possible that proton transfer occurs between non-H-bonded sites. This can lead to a H-bonding pattern that is no longer self-complementary. An example of this is found with a UPy we have made that contains a pyridinium redox couple attached to the pyrimidine ring in the UPy, UPyH(MeP+). This UPy was expected and confirmed by NMR to exhibit relatively weak dimerization in CH2Cl2 in the oxidized state due to the electrostatic repulsion and a weaker DADA H-bond motif. Dimerization strength was expected to increase upon reduction to the uncharged radical due to the loss of electrostatic repulsion and increased basicity of the H-acceptor sites. However, the voltammetry observed in CH2Cl2 is not consistent with this result. Furthermore, very similar voltammetry is observed in CH3CN, even though NMR shows only the monomer is present at the same concentrations in this solvent. Studies with model compounds strongly suggest that the reason for the failure to dimerize upon reduction is that the initial reduction product, an uncharged radical, is basic enough to be protonated by the oxidized starting material, resulting in a H-bonding motif that is no longer self-complementary. While this result negates the original goal of strengthening dimerization through reduction, it also opens up the intriguing possibility of switching binding partners by including a guest molecule that is not complementary to the oxidized UPyH(MeP+) form, but is complementary to the reduced, protonated UPyH2(MeP)+ form.