Remarkable interplay of redox states and conformational changes in a sterically crowded, cross-conjugated tetrathiafulvalene vinylog

Derivatives of 9-[2-(1,3-dithiol-2-ylidene)ethylidene]thioxanthene have been synthesized using Horner-Wadsworth-Emmons reactions of (1,3-dithiol-2-yl)phosphonate reagents with thioxanthen-9-ylidene-acetaldehyde (5). Further reactions lead to the sterically crowded cross-conjugated "vinylogous tetrathiafulvalene" derivative 9-[2,3-bis-(4,5-dimethyl-1,3-dithiol-2-ylidene)-propylidene]thioxanthene (10). X-ray crystallography, solution electrochemistry, optical spectroscopy, spectroelectrochemistry, and simultaneous electrochemistry and electron paramagnetic resonance spectroscopy, combined with theoretical calculations performed at the B3LYP/6-31G(d) level, elucidate the interplay of the electronic and structural properties in these molecules. For compound 10, multistage redox behavior is observed: the overall electrochemical process can be represented by 10-->10(.+)-->10(2+)-->10(4+) with good reversibility for the 10-->10(.+)-->10(2+) transformations. At the tetracation stage there is the maximum gain in aromaticity at the dithiolium and thioxanthenium rings. Theory predicts that for 10, 10(.+), and 10(2+) the trans isomers are more stable than the cis isomers (by ca. 2-18 kJ mol(-1)), whereas for 10(4+) the cis isomer becomes more stable than the trans isomer (by ca. 25 kJ mol(-1)) [trans and cis refer to the arrangement of the two dithiole moieties with respect to the central ==C(R)--C(H)== fragment]. These data explain the detection in cyclic voltammograms of both trans and cis isomers of 10 and 10(.+) during the reduction of 10(4+) at fast scan rates (>100 mV s(-1)) when the cis-trans isomerization is not completed within the timescale of the experiment. The X-ray structure of the charge-transfer complex (CTC) of 10 with 2,4,5,7-tetranitrofluorene-9-dicyanomethylenefluorene (DTeF) [stoichiometry: 10(.+)(DTeF)(2) (.-)2 PhCl] reveals a twisted conformation of 10(.+) (driven by the bulky thioxanthene moiety) and provides a very rare example of segregated stacking of a fluorene acceptor in a CTC.     

The role of hydrogen bonding in water-metal interactions

The hydrogen bond interaction between water molecules adsorbed on a Pd <111> surface, a nucleator of two dimensional ordered water arrays at low temperatures, is studied using density functional theory calculations. The role of the exchange and correlation density functional in the characterization of both the hydrogen bond and the water-metal interaction is analyzed in detail. The effect of non local correlations using the van der Waals density functional proposed by Dion et al. [M. Dion, H. Rydberg, E. Schr?der, D. C. Langreth and B. I. Lundqvist, Phys. Rev. Lett., 2004, 92, 246401] is also studied. We conclude that the choice of this potential is critical in determining the cohesive energy of water-metal complexes. We show that the interaction between water molecules and the metal surface is as sensitive to the density functional choice as hydrogen bonds between water molecules are. The reason for this is that the two interactions are very similar in nature. We make a detailed analogy between the water-water bond in the water dimer and the water-Pd bond at the Pd <111> surface. Our results show a strong similarity between these two interactions and based on this we describe the water-Pd bond as a hydrogen bond type interaction. These results demonstrate the need to obtain an accurate and reliable representation of the hydrogen bond interaction in density functional theory.     

Deciphering the role of hydrogen bonding in enhancing pDNA-polycation interactions

There is considerable interest in the binding and condensation of DNA with polycations to form polyplexes because of their possible application to cellular nucleic acid delivery. This work focuses on studying the binding of plasmid DNA (pDNA) with a series of poly(glycoamidoamine)s (PGAAs) that have previously been shown to deliver pDNA in vitro in an efficient and nontoxic manner. Herein, we examine the PGAA-pDNA binding energetics, binding-linked protonation, and electrostatic contribution to the free energy with isothermal titration calorimetry (ITC). The size and charge of the polyplexes at various ITC injection points were then investigated by light scattering and zeta-potential measurements to provide comprehensive insight into the formation of these polyplexes. An analysis of the calorimetric data revealed a three-step process consisting of two different endothermic contributions followed by the condensation/aggregation of polyplexes. The strength of binding and the point of charge neutralization were found to be dependent upon the hydroxyl stereochemistry of the carbohydrate moiety within each polymer repeat unit. Circular dichroism spectra reveal that the PGAAs induce pDNA secondary structure changes upon binding, which suggest a direct interaction between the polymers and the DNA base pairs. Infrared spectroscopy experiments confirmed both base pair and phosphate group interactions and, more specifically, showed that the stronger-binding PGAAs had more pronounced interactions at both sites. Thus, we conclude that the mechanism of poly(glycoamidoamine)-pDNA binding is most likely a combination of electrostatics and hydrogen bonding in which long-range Coulombic forces initiate the attraction and hydroxyl groups in the carbohydrate comonomer, depending on their stereochemistry, further enhance the association through hydrogen bonding to the DNA base pairs.     

Direct observation of mixed-valence and radical cation dimer states of tetrathiafulvalene in solution at room temperature: association and dissociation of molecular clip dimers under oxidative control

We have observed the mixed-valence and radical cation dimer states of a glycoluril-based molecular clip with tetrathiafulvalene (TTF) sidewalls at low concentration (1 mM) at room temperature. This molecular clip has four consecutive anodic steps in its cyclic voltammogram, which suggests a sequential oxidation of these TTF sidewalls to generate species existing in several distinct charge states: neutral monomers, mixed-valence dimers, radical cation dimers, and fully oxidized tetracationic monomers. The observation of characteristic NIR spectroscopic absorption bands at approximately 1650 and 830 nm in spectroelectrochemistry experiments supports the presence of intermediary mixed-valence and radical cation dimers, respectively, during the oxidation process. The stacking of four TTF radical cations in the dimer led to the appearance of a charge-transfer band at approximately 946 nm. Nanoelectrospray ionization mass spectrometry was used to verify the tricationic state and confirm the existence of other different charged dimers during the oxidation of the molecular clip.     

The photo-dissociation of the pyrrole-ammonia complex--the role of hydrogen bonding in Rydberg states photochemistry

The photochemistry of the pyrrole-ammonia cluster is analyzed theoretically. Whereas in neat pyrrole the dominant photochemical reaction is H-atom cleavage, recent experiments show that in pyrrole-ammonia clusters the major reaction is H-transfer to form the NH(4) radical (solvated by ammonia molecules in the case of large clusters) and the pyrrolyl radical. A mechanism involving the hydrogen-bonded Rydberg state is offered to account for these results and verified computationally. Two minima are located on the lowest excited singlet PES. Both of them are Rydberg states, one leads to the formation of NH(4) and pyrrolyl radicals, the other is connected to the πσ* state through a relatively high barrier, leading to a 3-body dissociation reaction to form a pyrrolyl radical, ammonia and an H-atom. The former is the energetically and statistically preferred one.     

An NMR investigation of the importance of intramolecular hydrogen bonding in determining the conformational equilibrium of ethylene glycol in solution

Although conformational analysis by NMR of ethylene glycol indicates generally strong preferences for the gauche conformation in solvents ranging from water to chloroform, the bulk of the NMR evidence indicates that intramolecular hydrogen bonding between the hydroxyl groups is unlikely to be a significant factor in determining that preference, except possibly in fairly non-polar solvents. The 'gauche effect' is clearly very important, especially in aqueous solution.     

Relative importance of hydrogen bonding and coordinating groups in modulating the zinc-water acidity

The presence of second-sphere -NH(2) groups in the proximity of a zinc(ii)-bound water molecule enhances its acidity by ca. 2 pK(a) units.     

Electrochemical measurement of switchable hydrogen bonding in an anthraquinone-based anion receptor

The electrochemistry of a novel anion receptor is presented. The receptor 1,3-diphenylcarboxamidoanthraquinone (AAR) in the absence of an appropriate anion behaves as an anthraquinone system in the presence of a strong hydrogen bond donor. In this case, the electrochemical evidence supports the suggestion that the hydrogen bonding with the anthraquinone occurs at least partially through intra- or intermolecular interactions. It is suggested that these interactions stabilise both the semiquinone and dianion species resulting from reduction of AAR. However, in the presence of a suitable competitive anion (specifically F⁻), the hydrogen-bond donor groups bind to the anion rather than the quinone oxygen atoms. This removes the hydrogen bonding interaction to the redox-active quinone centre and hence alters the electrochemistry significantly. In the presence of F⁻, two one-electron quasireversible electrochemical processes are observed.     

Crystal structures of dicarboxy-2,2'-bipyridyl complexes: the role of hydrogen bonding and stacking interactions

The crystal structures of three complexes of dicarboxy-2,2'-bipyridyl ligands, 5,5'-dicarboxy-2,2'-bipyridyl (1) and 4,4'-dicarboxy-2,2'-bipyridyl (2) are reported. [Rh(1H)3] shows two interpenetrating, homochiral rhombohedral networks linked by short carboxylate-carboxylic acid hydrogen bonds, in which each complex acts as a node for six hydrogen bonds. [Ru(1H2)(1H)2] forms only four such hydrogen bonds, leading to the formation of heterochiral chains held together by stacking between bipyridyls. [Co(2H)3] can in principle form six hydrogen bonds, but in practice forms only four in a layer structure where stacking interactions are important. This is attributed to differences in molecular shape.     

Disclosing the redox metabolism of drugs: The essential role of electrochemistry

Electrochemical methods provide a wide range of strategies to explore the metabolism of drugs. These approaches traditionally encompass preparative aspects viz. the electrochemical generation of potent metabolites or the electrochemical exploration of the reactivity of redox enzymes (or their mimics) toward drugs. More recently, the electroanalytical characterization of the successive redox and redox-coupled reactions was found effective to unravel more complex mechanisms, especially those related to the reactivity of bioorganometallic drugs. This minireview highlights the contribution of these different electrochemical strategies to the determination of drug metabolism through representative recent examples.     

Viscometric investigation of intramolecular hydrogen bonding cohesional entanglement in extremely dilute aqueous solution of poly vinyl alcohol

An investigation of influence of cryogenic treatment on extremely dilute aqueous solution of poly(vinyl alcohol) (PVA) was performed by viscometry. The solution was frozen in liquid nitrogen or in a freezer at −25°C, then thawed at ambient temperature and concentrated by evacuation. The viscosity of the solution was measured using the dilute method. The experimental results indicated that the viscosity of the solution is related to N, the times of the freezing and thawing cycle, and the temperature for freezing. Undergoing a treatment of freezing and thawing, the viscosity of the solution is decreased, while it can be recovered the value of before the treatment as the solution had been heated at a high temperature. Thus, a conclusion may be obtained; that is, for an extremely dilute aqueous solution of PVA, which concentration is below C_gel, threshold concentration for gelation, an intramolecular hydrogen bonding cohesional entanglement can be formed by freezing as N < 5. However, in the case of N > 5, it not only formed an intramolecular hydrogen bonding but also produced an intermolecular hydrogen bonding. At the same time, the abnormal behavior of reduced viscosity of the solution in extremely dilute concentration region has been explained. © 1997 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 35 : 2421–2427, 1997     

Revisiting the carboxylic acid dimers in aqueous solution: interplay of hydrogen bonding, hydrophobic interactions, and entropy

Carboxylic acid dimers are useful model systems for understanding the interplay of hydrogen bonding, hydrophobic effects, and entropy in self-association and assembly. Through extensive sampling with a classical force field and careful free energy analysis, it is demonstrated that both hydrogen bonding and hydrophobic interactions are indeed important for dimerization of carboxylic acids (except formic acid). The dimers are only weakly ordered, and the degree of ordering increases with stronger hydrophobic interactions between longer alkyl chains. Comparison of calculated and experimental dimerization constants reveals a systematic tendency for excessive self-aggregation in current classical force fields. Qualitative and quantitative information on the thermodynamics of hydrogen bonding and hydrophobic interactions derived from these simulations is in excellent agreement with existing results from experiment and theory. These results provide a verification from first principles of previous estimations based on two statistical mechanical hydrophobic theories. We also revisit and clarify the fundamental statistical thermodynamics formalism for calculating absolute binding constants, external entropy, and solvation entropy changes upon association from detailed free energy simulations. This analysis is believed to be useful for a wide range of applications including computational studies of protein-ligand and protein-protein binding.     

Specific photodynamics in thymine clusters: the role of hydrogen bonding

A photoionization detected IR study of thymine and 1-methylthymine monohydrates and of their homodimers was carried out to shed some light on the structure of the thymine clusters whose complex photodynamics has recently been the subject of great interest. Under supersonic jet conditions, thymine forms doubly H-bonded cyclic clusters with water or another base preferentially via its N1-H group and the adjacent carbonyl group. This hydrate is of no biological relevance since the N1-H group is the sugar binding site in thymidine. On the other hand, 1-methylthymine forms the donor H-bonds only via the N3-H group. Hence, properties of the N1-H and the N3-H bound clusters of thymine can be studied using thymine and 1-methylthymine molecules, respectively. No biologically relevant conformations of the dimers and hydrates of thymine, contrary to those of 1-methylthymine, are observed under supersonic jet conditions. Thymine homodimer, which extensively fragments upon UV ionization by formation of a protonated monomer, exhibits two N1-H···O═C2 hydrogen bonds. The photodynamics of hydrated thymines is found to be extremely sensitive to the hydration site: ranging from an ultrafast relaxation in less than 100 fs up to formation of a dark state with the lifetime on the microsecond time scale.     

Intramolecular interactions and intramolecular hydrogen bonding in conformers of gaseous glycine

Ab initio calculations at the MP2/6‐311++G** level of theory led recently to the identification of 13 stable conformers of gaseous glycine with relative energies within 11 kcal/mol. The stability of every structure depends on subtle intramolecular effects arising from conformational changes. These intramolecular interactions are examined with the tools provided by the Atoms In Molecules (AIM) theory, which allows obtaining a wealth of quantum mechanics information from the molecular electron density ρ( r ). The analysis of the topological features of ρ( r ) on one side and the atomic properties integrated in the basins defined by the gradient vector field of the density on the other side makes possible to explore the different intramolecular effects in every conformer. The existence of intramolecular hydrogen bonds on some conformers is demonstrated, while the presence of other stabilizing interactions arising from favorable conformations is shown to explain the stability of other structures in the potential energy surface of glycine. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 702–716, 2001     

Structural isomerism in crystals of redox-active secondary ortho-diamides: the role of competing intra- and intermolecular hydrogen bonds in directing crystalline topologies

The solid-state chemistry of a series of seven ortho-bis(alkylamido)ethylenedithiotetrathiafulvalene derivatives EDT-TTF-(CONHR)2 (R=Me, 1; Et, 2; Pr, 3; Bu, 4; Pent, 5; Hex, 6; and Bz, 7), in their neutral and one-electron-oxidized, radical cation states, was investigated with an eye on the topology of intra- and intermolecular hydrogen-bond motifs. In the case of neutral, monomolecular solids, an intramolecular N--H.O hydrogen bond seals a constrained seven-membered ring for 1, 2, 3, and 7, which is disrupted in butyl derivative 4 in favor of an antiparallel ladder at the expense of any intramolecular hydrogen bond. In the solid-state, the competition between intra- and intermolecular hydrogen bonding observed in solution depends on the packing of the molecules. Electrocrystallization of methyl derivative 1 with ReO4- or ClO4-, two anions of different volumes but otherwise identical charge and symmetry, revealed a fine sensitivity of the constrained seven-membered ring to the internal chemical pressure exerted by the anion. [1]2 *+ReO4 (sigmaRT=8.5 S cm(-1), activation energy Delta=600 K at high temperature) and beta"-[1]2 *+ClO4 (sigmaRT=0.03 S cm(-1), Delta=1600 K; under pressure at room temperature, the conductivity increases by three orders of magnitude up to 17 kbar with a linear variation of the activation energy with pressure, Delta=aP with a=0.202 10(6) K kbar(-1)) have vastly different architectures, dimensionalities, electronic structures, and collective properties, a consequence of the presence of the closed or open structural isomers in one or the other. This exemplifies the flexibility of functionalized TTF derivatives, even when the functional group is directly attached to the electro-active core. This allows an analogy to be drawn with tetrafunctionalized metallocenes, in which such flexibility has already been observed. The experimental data are supported by theoretical calculations of the energy profile of a model molecule on rotation of the amido groups.     

On modulating the self-assembly behaviors of poly(styrene-b-4-vinylpyridine)/octyl gallate blends in solution state via hydrogen bonding from different common solvents

We have investigated the complexation-induced phase behavior of the mixtures of poly(styrene-b-4-vinylpyridine) (PS-b-P4VP) and octyl gallate (OG) due to hydrogen bonding in different solvents. The Fourier transform infrared spectroscopic result indicates that the hydrogen-bonding was formed between the P4VP blocks and OG in both THF and DMF, implying the P4VP blocks can bind to OG. For PS-b-P4VP/OG mixture in chloroform, the morphological transitions were induced from the unimer configuration to swollen aggregate and complex-micelles by adding OG. Interestingly, the complex-micelles can lead the formation of the honeycomb structure from chloroform solution. The PS-b-P4VP/OG mixture in THF, behaving an amphiphilic diblock copolymer in solution state, exhibited a series of morphological transitions from sphere, pearl-necklace-liked rod, worm-liked rod, vesicle, to core-shell-corona aggregates by increasing the OG content. In contrast, the PS-b-P4VP/OG mixture in DMF maintained the unimer configuration upon adding OG. Therefore, the complexation-induced morphology of the mixtures of PS-b-P4VP and OG can be mediated by adopting different common solvents to affect the self-assembly behavior.