The effect of polarization on multiple hydrogen-bond formation in models of self-assembling materials

We report density functional theory calculations at the B3LYP/D95(d,p) level on several different cyclic H-bonding dimers, where the monomers of each are connected by a pair of N-H···O=C H-bonding interactions, and the H-bonding donors and acceptors on each monomer are separated by polarizable spacers. Depending on the structures, the individual H-bonds vary in strength (enthalpy) by over a factor of four, from 2.41 to 10.99 kcal/mol. We attribute most of the variation in interaction energies to differences in the extent of polarization due to each of the H-bonds, which can either combine constructively or destructively. The dipole-dipole interactions between the pair of H-bonds also contribute somewhat to the relative stabilities. The relevance of these results to the design of self-assembling materials is discussed.     

Theoretical study of cooperativity in biotin

To give a deeper insight into the widely discussed catalytic mechanism of biotin, four representative model molecules and their aggregates hydrogen bonding (H-bonding) to water molecules were investigated by means of ab initio calculations and compared with molecular dynamics simulations. The roles of the ureido group, the sulfur atom, and the side chain of biotin are examined and discussed, respectively. Some significant H-bonding cooperativities are theoretically demonstrated in the ureido group of biotin. The pi-electron delocalization of the ureido group makes the system a good candidate for the H-bonding cooperativities, which in turn increases the covalent character of the corresponding H-bonds and facilitates the electrophilic substitution of the nitrogen atoms in the ureido group. The sulfur of biotin may participate in the delocalized pi-electron system of the ureido group via special sulfur-nitrogen bonding interactions, which reinforces the H-bonding cooperativities of the ureido group. The side chain of biotin not only reduced the accessibility of 3-NH due to steric hindrance but also enhanced the H-bonding cooperativities of the ureido group by folding over to hydrogen bond to more water molecules. The folded states are a probable way of activating 1-NH by strong cooperative effects. In addition, the H-bonding cooperativities may be a significant reason for the strong and specific binding between biotin and streptavidin.     

Cooperative 4-pyridone H-bonds with extraordinary stability. A DFT molecular orbital study

The N-H...O H-bonding enthalpy between 4-pyridones connected in a chain of H-bonds can achieve 23 kcal/mol for the most central H-bonds, while that between two 4-pyridones is 9.90 kcal/mol based upon DFT calculations on the counterpoise-corrected potential energy surfaces. That the range of enthalpies for N-H...O H-bonds can vary from as little as 2 to as much 23 kcal/mol depends primarily upon the polarizability of whatever internally connects the N-H and C=O within the H-bonding molecule, which are two parallel -C=C- entities in 4-pyridone. The contribution of covalent or charge-transfer interactions between the pi-systems of adjacent 4-pyridones is small.     

Probing the competition between secondary structures and local preferences in gas phase isolated peptide backbones

Combining laser desorption with a supersonic expansion together with the selectivity of IR/UV double resonance spectroscopy makes it possible to isolate and characterise the gas phase of remarkable backbone conformations of short peptide chains mimicking protein segments. A systematic bottom-up approach involving a conformer-specific IR study of peptide sequences of increasing sizes has enabled us to map the spectral signatures of the intramolecular interactions, which shape the peptide backbone, in particular H-bonds. The precise data collected are directly comparable to the most sophisticated quantum chemistry calculations of these species and therefore constitute a stringent test for the theoretical methods used. One-residue chains reveal the local conformational preference of the backbone and its dependence upon the nature of the residue. The investigation of longer chains provides evidence for a competition between simple successions of local conformational preferences along the chain and more folded structures, in which a new H-bonding network, involving distant H-bonding sites along the backbone, takes place. From three residues, the issue of helical folding can also be addressed. The present review of the gas phase literature data emphasizes the observation of remarkable secondary structures of biology, including short segments of beta-strands, gamma- and beta-turns, combinations of turns, including a 3(10) helix. It also provides evidence for the flexibility of the peptide chains, i.e., a critical influence of rather minor interactions (like side-chain/backbone interactions) on the conformational stability. Finally, the paper will discuss future promising directions of the present approach.     

Spectroscopic evidence for gas-phase formation of successive beta-turns in a three-residue peptide chain

We report the first gas-phase spectroscopic study of a three-residue model of a peptide chain, Ac-Phe-Gly-Gly-NH2 (Ac = acetyl), using the IR/UV double resonance technique. The existence of at least five different conformers under supersonic expansion conditions is established, most of them exhibiting rather strong intramolecular H-bonds. One of the most populated conformers, however, exhibits a different H-bonding network characterized by two weak H-bonds. Comparison of the amide A and I/II experimental data with density functional theory calculations carried out on a series of selected conformations enables us to assign this conformer to two successive beta-turns along the peptide chain, the two H-bonds being of C10 type, i.e., each of them closing a 10-atom ring in the molecule. The corresponding form is found to be more stable than the 310 helix secondary structure (not observed), presumably because of specific effects due to the glycine residues.     

Influence of H-bond strength on chelate cooperativity

Intermolecular complexes formed between metalloporphyrins and pyridine ligands equipped with multiple H-bond donors and acceptors have been used to measure the free energy contributions due to intramolecular ether-phenol H-bonding in the 24 different supramolecular architectures using chemical double mutant cycles in toluene. The ether-phenol interactions are relatively weak, and there are significant populations of partially bound states where between zero and four intramolecular H-bonds are made in addition to the porphyrin-ligand coordination interaction. The complexes were analyzed as ensembles of partially bound states to determine the effective molarities for the intramolecular interactions by comparison with the corresponding intermolecular ether-phenol H-bonds. The properties of the ether-phenol interactions were compared with phosphonate diester-phenol interactions in a closely related ligand system, which has more powerful H-bond acceptor oxygens positioned at the same location on the ligand framework. This provides a comparison of the properties of weak and strong H-bonds embedded in the same 24 supramolecular architectures. When the product of the intermolecular association constant and the effective molarity KEM > 1, there is a linear increase in the free energy contribution due to H-bonding with log EM, because the intramolecular interactions contribute fully to the stability of the complex. When KEM < 1, the H-bonded state is not significantly populated, and there is no impact on the overall stability of the complex. Intermolecular phosphonate diester-phenol H-bonds are 2 orders of magnitude stronger than ether-phenol H-bonds in toluene, so for the phosphonate diester ligand system, 23 of the 24 supramolecular architectures make intramolecular H-bonds. However, only 8 of these architectures lead to detectable H-bonding in the ether ligand system. The other 15 complexes have a suitable geometry for formation of H-bonds, but the ether-phenol interaction is not strong enough to overcome the reorganization costs associated with making intramolecular contacts, i.e., KEM < 1 for the ether ligands, and KEM > 1 for the phosphonate diester ligands. The values of EM measured for two different types of H-bond acceptor are linearly correlated, which suggests that EM is a property of the supramolecular acrchitecture. However, the absolute value of EM for an intramolecular phosphonate diester H-bond is about 4 times lower than the corresponding value for an intramolecular ether-phenol interaction embedded in the same supramolecular framework, which suggests that there may be some interplay of K and EM.     

Through hydrogen-bond vibrational coupling in hydrogen-bonding chains of 4-pyridones with implications for peptide amide I absorptions: density functional theory compared with transition dipole coupling

We present B3LYP/D95** calculations on the C=O and N-H couplings in H-bonded chains of 4-pyridones. 14C-substitutions are used to decouple various vibrations for purposes of illustration. The coupled C=O vibrations bear analogy to the amide I bands of proteins and peptides. The coupling of the C=O's occurs primarily via the cooperative H-bonds rather than transition dipole coupling (TDC), as demonstrated by the fact that (1) the couplings are greater than previously reported for similar studies on formamides despite the larger distance between the C=O's in the pyridone chains (TDC coupling decreases with distance) and (2) the red shifts (also greater than for formamides) can be attributed to the changes in the geometries (particularly the C=O bond lengths) of the individual 4-pyridones in the H-bonding chains induced by the H-bonds and resulting polarization of the monomers.     

Attractive strain: the disadvantages of rigid multiple H-bond donors and acceptors. A theoretical analysis of the hydrogen-bonding interactions in complexes of tetraazaanthracenedione with pyridylureas

We report density functional theory calculations at the B3LYP/D95(d,p) level on the hydrogen-bonding complexes of tetraazaanthracenedione, 1, with N-(pyridin-2-yl)urea, 2H, or N-(6-aminopyridin-2-yl)urea, 2N. The interaction energy of the 1-2H complex exceeds that of 1-2N, despite the fact that 1-2N contains a strong N-H...O interaction in place of a weak C-H...O interaction in 1-2H. We show that the 1-2N interaction is weaker than the sum of the four normal individual H-bonding interactions because the steric constraints of the complex prevent the H-bonding donors and acceptors from optimally approaching each other to form the two central H-bonds. This steric phenomenon, which we call attractive strain, is likely present to some extent in most H-bonding systems that contain more than two H-bonds between rigid monomers. Attractive strain is unusually important in 1-2N. Attractive strain can be conceived of as an enthalpic cost for the entropic benefits of freezing the dihedral angles of the multiple H-bond donors and acceptors by designing rigid systems.     

Molecular basis of the recognition process: hydrogen-bonding patterns in the guanine primary recognition site of ribonuclease T1

Investigation of the intrinsic H-bonding pattern of the guanine complex with a sizable segment (from Asn43 to Glu46) of the primary recognition site (PRS) in RNase T1 at the B3LYP/6-311G(d,p) level of theory enables the electronic density characteristics of the H-bonding patterns of the guanine-PRS complexes to be identified. The perfect H-bonding pattern in the guanine recognition site is achieved through the guanine complex interactions with the large segment of the PRS. Two significant short H-bonds, O epsilon 1...HN1 and O epsilon 2...HN2, have been identified. The similar short H-bond distances found in the anionic GC- base pair and in this study suggest that the short hydrogen-bond distances may be characteristic of the multiple H-bonded anionic nucleobases. The H-bonding energy distribution, the geometric analysis of the H-bonding pattern, and the electron structure characteristics of the H-bonds in the guanine PRS of RNase T1 all suggest that the O epsilon 1...HN1 and O epsilon 2...HN2 side-chain H-bonds dominate the binding at the guanine recognition site of RNase T1. Also, the geometry evidence, the electron structure characteristics, and the properties of the bond critical points of the H-bonds reveal that the side-chain H-bonding and the main-chain H-bonding are mutually intensifying. Thus the positive cooperativity between Asn43 to Tyr45 and Glu46 is proposed.     

S K-edge XAS and DFT calculations on square-planar NiII-thiolate complexes: effects of active and passive H-bonding

S K-edge XAS for a low-spin NiII-thiolate complex shows a 0.2 eV shift to higher pre-edge energy but no change in Ni-S bond covalency upon H-bonding. This is different from the H-bonding effect we observed in high-spin FeIII-thiolate complexes where there is a significant decrease in Fe-S bond covalency but no change in energy due to H-bonding (Dey, A.; Okamura, T.-A.; Ueyama, N.; Hedman, B.; Hodgson, K. O.; Solomon, E. I. J. Am. Chem. Soc. 2005, 127, 12046-12053). These differences were analyzed using DFT calculations, and the results indicate that two different types of H-bonding interactions are possible in metal-thiolate systems. In the high-spin FeIII-thiolate case, the H-bonding involves a thiolate donor orbital which is also involved in bonding with the metal (active), while in the low-spin NiII-thiolate, the orbital involved in H-bonding is nonbonding with respect to the M-S bonding (passive). The contributions of active and passive H-bonds to the reduction potential and Lewis acid properties of a metal center are evaluated.     

Insights into hydrogen bonding and stacking interactions in cellulose

In this quantum chemical study, we explore hydrogen bonding (H-bonding) and stacking interactions in different crystalline cellulose allomorphs; namely, cellulose I(β) and cellulose III(I). We consider a model system representing a cellulose crystalline core made from six cellobiose units arranged in three layers with two chains per layer. We calculate the contributions of intrasheet and intersheet interactions to the structure and stability in both cellulose I(β) and cellulose III(I) crystalline cores. Reference structures for this study were generated from molecular dynamics simulations of water-solvated cellulose I(β) and III(I) fibrils. A systematic analysis of various conformations describing different mutual orientations of cellobiose units is performed using the hybrid density functional theory with the M06-2X with 6-31+G(d,p) basis sets. We dissect the nature of the forces that stabilize the cellulose I(β) and cellulose III(I) crystalline cores and quantify the relative strength of H-bonding and stacking interactions. Our calculations demonstrate that individual H-bonding interactions are stronger in cellulose I(β) than in cellulose III(I); however, the total H-bonding contribution to stabilization is larger in cellulose III(I) because of the highly cooperative nature of the H-bonding network. In addition, we observe a significant contribution from cooperative stacking interactions to the stabilization of cellulose I(β). The theory of atoms-in-molecules (AIM) has been employed to characterize and quantify these intermolecular interactions. AIM analyses highlight the role of nonconventional CH···O H-bonding in the cellulose assemblies. Finally, we calculate molecular electrostatic potential maps for the cellulose allomorphs that capture the differences in chemical reactivity of the systems considered in our study.     

Dissection of complex molecular recognition interfaces

The synthesis of a family of zinc porphyrins and pyridine ligands equipped with peripheral H-bonding functionality has provided access to a wide range of closely related supramolecular complexes featuring between zero and four intramolecular H-bonds. An automated UV/vis titration system was used to characterize 120 different complexes, and these data were used to construct a large of number of different chemical double mutant cycles to quantify the intramolecular H-bonding interactions. The results probe the quantitative structure-activity relationship that governs cooperativity in the assembly of complex molecular recognition interfaces. Specifically, variations in the chemical structures of the complexes have allowed us to change the supramolecular architecture, conformational flexibility, geometric complementarity, the number and nature of the H-bond interactions, and the overall stability of the complex. The free energy contributions from individual H-bonds are additive, and there is remarkably little variation with architecture in the effective molarity for the formation of intramolecular interactions. Intramolecular H-bonds are not observed in complexes where they are geometrically impossible, but there are no cases where excellent geometric complementarity leads to very high affinities. Similarly, changes in conformational flexibility seem to have limited impact on the values of effective molarity (EM). The major variation that was found for all of the 48 intramolecular interactions that were examined using double mutant cycles is that the values of EM for intramolecular carboxylate ester-phenol H-bonds (200 mM) are an order of magnitude larger than those found for phosphonate diester-phenol H-bonds (30 mM). The corresponding intermolecular phosphonate diester-phenol H-bonds are 2 orders of magnitude more stable than carboxylate ester-phenol H-bonds, and the large differences in EM may be due to some kind of compensation effect, where the stronger H-bond is harder to make, because it imposes tighter constraints on the geometry of the complex.     

The special features of H-bonding in supercritical water close to the saturation curve

A complex study of H-bonding in supercritical water in the region close to the saturation curve was performed at constant pressures of 30 and 50 MPa and a constant temperature of 673 K. The topological H-bond characteristics were calculated by the molecular dynamics method with the use of the TIP4P-HB potential. The calculations included the number of H-bonds per water molecule, the degree of H-bonding, and the distributions of molecules according to the number of H-bonds (fractions and the gradients of fractions of molecules with n H-bonds). Changes in these characteristics as the temperature, density, and pressure varied were studied.     

Assembling phenomena of calix[4]hydroquinone nanotube bundles by one-dimensional short hydrogen bonding and displaced pi-pi stacking

Using the computer-aided molecular design approach, we recently reported the synthesis of calix[4]hydroquinone (CHQ) nanotube arrays self-assembled with infinitely long one-dimensional (1-D) short hydrogen bonds (H-bonds) and aromatic-aromatic interactions. Here, we assess various calculation methods employed for both the design of the CHQ nanotubes and the study of their assembly process. Our calculations include ab initio and density functional theories and first principles calculations using ultrasoft pseudopotential plane wave methods. The assembly phenomena predicted prior to the synthesis of the nanotubes and details of the refined structure and electronic properties obtained after the experimental characterization of the nanotube crystal are reported. For better characterization of intriguing 1-D short H-bonds and exemplary displaced pi-pi stacks, the X-ray structures have been further refined with samples grown in different solvent conditions. Since X-ray structures do not contain the positions of H atoms, it is necessary to analyze the system using quantum theoretical calculations. The competition between H-bonding and displaced pi-pi stacking in the assembling process has been clarified. The IR spectroscopic features and NMR chemical shifts of 1-D short H-bonds have been investigated both experimentally and theoretically. The dissection of the two most important interaction components leading to self-assembly processes would help design new functional materials and nanomaterials.     

A critical examination of H-bonding interactions calculated using the AM1 molecular orbital method

AM 1 calculations for various intermolecular and internally hydrogen-bonding species are compared with experiment. The calculations generally provide a useful, but not perfect, means for modeling H-bonds. The average stabilization energy for 33 gas-phase hydrations of ions was 1.4, whereas that for amination of 10 ions was 4.2 kcal/mol, too weak when compared to experimental results. H-bonding distances have a tendency to be long. The tendency of AM 1 to predict multicentered H-bonds is discussed in the context of recent surveys of crystallographic data banks. Caution is recommended in comparing AM 1 results with inappropriate experiments and inadequate ab initio calculations. © 1992 John Wiley & Sons, Inc.     

Hydrogen-bonding interactions in ferrocene-peptide conjugates containing valine

The synthesis and characterization of a series of ferrocene (Fc) peptide conjugates containing the amino acid valine is reported, where the peptide substituents are part of the hydrophobic sequence of the amyloid β-peptide. The hydrogen-bonding (H-bonding) interaction in these compounds is studied by variable temperature ¹H NMR spectroscopy. The solid-state structures, determined by single crystal X-ray crystallography, of two of the conjugates (Fc[CO-Leu-Val-OMe]₂1 and Fc[CO-Gly-Val-OH]₂6) are reported. Both structures are stabilized by intramolecular H-bonds exhibiting the familiar “Herrick motif” involving the proximal amide NH and the amide CO of the adjacent amino acid. This motif is sufficiently rigid and is maintained in solution as suggested by CD studies. However, the intermolecular H-bonding patterns observed on conjugates 1 and 6 are significantly different resulting in very different supramolecular architectures. For conjugate 1, a more conventional set of head-to-tail stacking interactions which is stabilized by β-sheet-like H-bonding interactions between the individual molecules is observed. However, for conjugate 6, the presence of the C-terminal acid group and presumably the flexibility of the Gly linker enables the formation of a more open structure that contains hydrophobic channels occupied by solvent molecules.     

Steric desolation enhances the effective molarities of intramolecular H-bonding interactions

Free energy contributions due to intramolecular phosphonate diester-phenol H-bonds have been measured for 20 different supramolecular architectures in cyclohexanone solution. High throughput UV/Vis titrations were used in combination with chemical double mutant cycles to dissect out the contributions of different functional group interactions to the stabilities of over 100 different zinc porphyrin-pyridine ligand complexes. These complexes have previously been characterised in toluene and in 1,1,2,2-tetrachloroethane (TCE) solution. Intramolecular ester-phenol H-bonds that were measured in these less polar solvents are too weak to be detected in cyclohexanone, which is a more competitive solvent. The stability of the intermolecular phosphonate diester-phenol H-bond in cyclohexanone is an order of magnitude lower than in TCE and two orders of magnitude lower than in toluene. As a consequence, only seven of the twenty intramolecular phosphonate diester-phenol interactions that were previously measured in toluene and TCE could be detected in cyclohexanone. The effective molarities (EM) for these intramolecular interactions are different in all three solvents. Determination of the EM accounts for solvent effects on the strengths of the individual H-bonding interactions and the zinc porphyrin-pyridine coordination bond, so the variation in EM with solvent implies that differences in the solvation shells make significant contributions to the overall stabilities of the complexes. The results suggest that steric effects lead to desolvation of bulky polar ligands. This increases the EM values measured in TCE, because ligands that fail to replace the strong interactions made with this solvent are unusually weakly bound compared with ligands that make intramolecular H-bonds.     

Direct evaluation of individual hydrogen bond energy in situ in intra- and intermolecular multiple hydrogen bonds system

The results of evaluating the individual hydrogen bond (H-bond) strength are expected to be helpful for the rational design of new strategies for molecular recognition or supramolecular assemblies. Unfortunately, there is few obvious and unambiguous means of evaluating the energy of a single H-bond within a multiple H-bonds system. We present a local analytic model, ABEEMσπ H-bond energy (HBE) model based on ab initio calculations (MP2) as benchmark, to directly and rapidly evaluate the individual HBE in situ in inter- and intramolecular multiple H-bonds system. This model describes the HBE as the sum of electrostatic and van der Waals (vdW) interactions which all depend upon the geometry and environment, and the ambient environment of H-bond in the model is accounted fairly. Thus, it can fairly consider the cooperative effect and secondary effect. The application range of ABEEMσπ HBE model is rather wide. This work has discussed the individual H-bond in DNA base pair and protein peptide dimers. The results indicate that the interactions among donor H atom, acceptor atom as well as those atoms connected to them with 1,2 or 1,3 relationships are all important for evaluating the HBE, although the interaction between the donor H atom and the acceptor atom is large. Furthermore, our model quantitatively indicates the polarization ability of N, O, and S in a new style, and gives the percentage of the polarization effect in HBE, which can not be given by fixed partial charge force field.     

Conformational study of a guaiacyl beta-O-4 lignin model compound by NMR. Examination of intramolecular hydrogen bonding interactions and conformational flexibility in solution

Intramolecular H-bonding interactions were investigated in solution for the threo and erythro diastereomeric forms of a guaiacyl beta-O-4 lignin model compound by using the NMR data obtained from hydroxyl protons. Temperature coefficients of the chemical shifts (ddelta/dT) and coupling constants (3J(HCOH)) were measured in aprotic and protic solutions: DMSO-d6, acetone-d6 and acetone-d6-water. The NMR parameters do not support the existence of strong and persistent intramolecular H-bonds that could participate in the stabilization of the guaiacyl beta-O-4 structure in solution, but instead indicate that intermolecular H-bonds to solvent predominate. 1D NOE experiments nevertheless revealed the presence of a direct chemical exchange between the hydroxyl protons, suggesting the possible existence of weak and transient intramolecular H-bonding interactions. The conformational flexibility of the threo structure was also investigated in acetone solution from the measurement of long-range 1H, 1H and 1H, 13C coupling constants and from NOESY experiments. The NMR data are not consistent with any single conformation, indicating that different conformers co-exist in solution. The experimental results support the conformational flexibility predicted by molecular dynamics simulations performed in a previous study. Finally, both experimental and theoretical approaches indicate that weak intramolecular H-bonds can exist transiently in solution, breaking and reforming as the beta-O-4 molecule undergoes conformational interconversion, but cannot be invoked as possible means of conferring rigidity to the beta-O-4 structure.     

Gas-phase DNA oligonucleotide structures. A QM/MM and atoms in molecules study

QM/MM calculations have been employed to investigate the role of hydrogen bonding and pi-stacking in single- and double-stranded DNA oligonucleotides. DFT calculations and Atoms in Molecules analysis on QM/MM-optimized structures allow characterization and estimation of the energies of pi-stacking and hydrogen-bond interactions. This shows that pi-stacking interactions depend on the number and the nature of the DNA bases for single-stranded nucleotides; for instance, guanines are found to be involved in strong hydrogen bonds, whereas adenines interact mainly via stacking interactions. The role of interbase hydrogen bonding was explored: the -NH2 groups of guanine, adenine, and cytosine participate in N-H...O and N-H...N interactions. These are much stronger in single-strand oligonucleotides, where the -NH2 groups are highly nonplanar. In double-stranded DNA, the strong base-pairing hydrogen bonds of complementary bases lead to more planar -NH2 groups, which tend to be involved in pi-stacking interactions rather than H-bonds. The use of AIM also allows us to evaluate the interplay of pi-stacking and H-bonding, suggesting that cooperativity does occur, but is generally limited to about 1-2 kcal/mol.