Effects of hydrogen-bonding and stacking interactions with amino acids on the acidity of uracil

The effects of hydrogen-bonding interactions with amino acids on the (N1) acidity of uracil are evaluated using (B3LYP) density functional theory. Many different binding arrangements of each amino acid to three uracil binding sites are considered. The effects on the uracil acidity are found to significantly depend upon the nature of the amino acid and the binding orientation, but weakly depend on the binding site. Our results reveal that in some instances small models for the amino acids can be used, while for other amino acids larger models are required to properly describe the binding to uracil. The gas-phase acidity of uracil is found to increase by up to approximately 60 kJ mol(-1) due to discrete hydrogen-bonding interactions. Although (MP2) stacking interactions with aromatic amino acids decrease the acidity of uracil, unexpected increases in the acidity are found when any of the aromatic amino acids, or the backbone, hydrogen bond to uracil. Consideration of enzymatic and aqueous environments leads to decreases in the effects of the amino acids on the acidity of uracil. However, we find that the magnitude of the decrease varies with the nature of the molecule bound, as well as the (gas-phase) binding orientations and strengths, and therefore solvation effects should be considered on a case-by-case basis in future work. Nevertheless, the effects of amino acid interactions within enzymatic environments are as much as approximately 35 kJ mol(-1). The present study has general implications for understanding the nature of active site amino acids in enzymes, such as DNA repair enzymes, that catalyze reactions involving anionic nucleobase intermediates.     

Effects of hydrogen bonding on the acidity of adenine, guanine, and their 8-oxo derivatives

Complexes between ammonia, water, or hydrogen fluoride and adenine, guanine, or their 8-oxo derivatives are investigated using density-functional theory. The binding strengths of the neutral and (N9) anionic complexes are considered for a variety of purine binding sites. The effects of hydrogen-bonding interactions on the (N9) acidity of the purine derivatives are considered as a function of the molecule bound and the binding site. It is found that hydrogen-bonding interactions with one molecule can increase the acidity of purine derivatives by up to 60 kJ mol(-1). The (calculated) simultaneous effects of up to four molecules on the acidity of the purine derivatives are also considered. Our data suggest that the effects of more than one molecule on the acidity of the purines are generally less than the sum of the individual (additive) effects, where the magnitude of the deviation from additivity increases with the number, as well as the acidity, of molecules bound. Nevertheless, the increase in the acidity due to additional hydrogen-bonding interactions is significant, where the effect of two, three, or four hydrogen-bonding interactions can be as large as approximately 95, 115, and 130 kJ mol(-1), respectively. The present study provides a greater fundamental understanding of hydrogen-bonding interactions involving the natural purines, as well as those generated through oxidative DNA damage, which may aid the understanding of important biological processes.     

A kinetic and thermodynamic study of the glycosidic bond cleavage in deoxyuridine

Density functional theory was used to study the thermodynamics and kinetics for the glycosidic bond cleavage in deoxyuridine. Two reaction pathways were characterized for the unimolecular decomposition in vacuo. However, these processes are associated with large reaction barriers and highly endothermic reaction energies, which is in agreement with experiments that suggest a (water) nucleophile is required for the nonenzymatic glycosidic bond cleavage. Two (S(N)1 and S(N)2) reaction pathways were characterized for direct hydrolysis of the glycosidic bond by a single water molecule; however, both pathways also involve very large barriers. Activation of the water nucleophile via partial proton abstraction steadily decreases the barrier and leads to a more exothermic reaction energy as the proton affinity of the molecule interacting with water increases. Indeed, our data suggests that the barrier heights and reaction energies range from that for hydrolysis by water to that for hydrolysis by the hydroxyl anion, which represents the extreme of (full) water activation (deprotonation). Hydrogen bonds between small molecules (hydrogen fluoride, water, or ammonia) and the nucleobase were found to further decrease the barrier and overall reaction energy but not to the extent that the same hydrogen-bonding interactions increase the acidity of the nucleobase. Our results suggest that the nature of the nucleophile plays a more important role in reducing the barrier to glycosidic bond cleavage than the nature of the small molecule bound, and models with more than one hydrogen fluoride molecule interacting with the nucleobase provide further support for this conclusion. Our results lead to a greater fundamental understanding of the effects of the nucleophile, activation of the nucleophile, and interactions with the nucleobase for this important biological reaction.     

Computational comparison of the stacking interactions between the aromatic amino acids and the natural or (cationic) methylated nucleobases

The strongest gas-phase MP2/6-31G*(0.25) stacking energies between the aromatic amino acids and the natural or methylated nucleobases were considered. The potential energy surfaces of dimers were searched as a function of the vertical separation, angle of rotation and horizontal displacement between monomers stacked according to their centers of mass. Our calculations reveal that the stacking interactions of adducts for a given nucleobase are dependent on the methylation site (by up to 20 kJ mol(-1)), where the relative magnitudes of the interactions are determined by the dipole moments of the adducts and the proton affinities of nucleobase methylation sites. Nevertheless, the differences in the (gas-phase) stacking of methylated adducts are small compared with the differences between the stacking of the corresponding natural and methylated nucleobases. Indeed, methylation increases the stacking energy by up to 40 kJ mol(-1) (or 135%). Although immersing the dimers in different solvents decreases the gas-phase stacking energies with an increase in the polarity of the environment, base methylation still has a significant effect on the nucleobase stacking ability in solvents with large dipole moments, and, perhaps more importantly, environments that mimic enzyme active sites. Our results shed light on the workings of DNA repairs enzymes that selectively remove a wide variety of alkylated nucleobases over the natural bases.     

A computational characterization of the hydrogen-bonding and stacking interactions of hypoxanthine

The hydrogen-bonding and stacking interactions of hypoxanthine, a potential universal nucleobase, were calculated using a variety of methodologies (CCSD(T), MP2, B3LYP, PWB6K, AMBER). All methods predict that the hydrogen-bonding interaction in the hypoxanthine-cytosine pair is approximately 25 kJ mol(-1) stronger than that in the other dimers. Although the calculations support suggestions from experiments that hypoxanthine preferentially binds with cytosine, the trend in the calculated hydrogen-bond strengths for the remaining natural nucleobases do not show a strong correlation with the experimentally predicted binding preferences. However, our calculations suggest that the stacking interactions of hypoxanthine are similar in magnitude to the hydrogen-bonding interactions at all levels of theory (with the exception of B3LYP, which incorrectly predicts stacked dimers to be unstable). Therefore, stacking interactions should also be considered when analyzing the stability of DNA helices containing hypoxanthine and the use of larger models that account for both hydrogen-bonding and stacking within DNA duplexes will likely result in better agreement with experimental observations. For the majority of the dimers, PWB6K and AMBER provide reasonable binding strengths at reduced computational costs, and therefore will be useful techniques for considering larger models.     

A computational proposal for the experimentally observed discriminatory behavior of hypoxanthine, a weak universal nucleobase

A computational model composed of six nucleobases was used to investigate why hypoxanthine does not yield duplexes of equal stability when paired opposite each of the natural DNA nucleobases. The magnitudes of all nearest-neighbor interactions in a DNA helix were calculated, including hydrogen-bonding, intra- and interstrand stacking interactions, as well as 1-3 intrastrand stacking interactions. Although the stacking interactions in DNA relevant arrangements are significant and account for at least one third of the total stabilization energy in our nucleobase complexes, the trends in the magnitude of the stacking interactions cannot explain the relative experimental melting temperatures previously reported in the literature. Furthermore, although the total hydrogen-bonding interactions explain why hypoxanthine preferentially pairs with cytosine, the experimental trend for the remaining nucleobases (A, T, G) is not explained. In fact, the calculated pairing preference of hypoxanthine matches that determined experimentally only when the sum of all types of nearest-neighbor interactions is considered. This finding highlights a strong correlation between the relative magnitude of the total nucleobase-nucleobase interactions and measured melting temperatures for DNA strands containing hypoxanthine despite the potential role of other factors (including hydration, temperature, sugar-phosphate backbone). By considering a large range of sequence combinations, we reveal that the binding preference of hypoxanthine is strongly dependent on the nucleobase sequence, which may explain the varied ability of hypoxanthine to universally bind to the natural bases. As a result, we propose that future work should closely examine the interplay between the dominant nucleobase-nucleobase interactions and the overall strand stability to fully understand how sequence context affects the universal binding properties of modified bases and to aid the design of new molecules with ambiguous pairing properties.     

How do size-expanded DNA nucleobases enhance duplex stability? Computational analysis of the hydrogen-bonding and stacking ability of xDNA bases

Computational chemistry (B3LYP, MP2) is used to study the properties of size-expanded DNA nucleobases generated by inserting a benzene spacer into the natural nucleobases. Although the addition of the spacer does not significantly affect the hydrogen-bonding properties of natural nucleobases, the orientation of the base about the glycosidic bond necessary for Watson-Crick binding is destabilized, which could have implications for the selectivity of expanded bases, as well as the stability of expanded duplexes. Consideration of the (stacked) binding energies in the preferred relative orientation of natural and expanded nucleobases aligned according to their centers of mass reveals that the stacking within natural dimers can be increased by up to 50% upon expansion of one nucleobase and up to 90% upon expansion of two nucleobases. The implications of these findings to the stability of expanded duplexes were revealed by considering simplified models of natural and mixed duplexes composed of four nucleobases. Although intra- and interstrand interactions within double helices are typically less than those predicted when nucleobases are stacked according to their centers of mass, some nucleobases utilize their full stacking potential within double helices, where both intra- and interstrand interactions can be significant. Most importantly, increasing the size of nucleobases within the duplex significantly increases both intra- and interstrand stacking interactions. Specifically, some interactions are double the magnitude of the corresponding intrastrand interactions in natural helices, and even greater increases in interstrand interactions are sometimes found. Thus, our work suggests that mixed duplexes composed of natural bases hydrogen bound to expanded bases may exploit the increase in the inherent stacking ability of the expanded bases in more than one way and thereby afford duplexes with greater stability than natural DNA.     

Insights into DNA binding of ruthenium arene complexes: role of hydrogen bonding and pi stacking

Density functional theory (DFT) methods are used to investigate the binding of ruthenium arene complexes, proposed as promising anticancer drugs, to isolated nucleobases. This shows a clear preference for binding at guanine over any other base and an approximately 100 kJ mol (-1) difference in binding between guanine and adenine in the gas phase, while binding to cytosine and inosine are intermediate in energy between these extremes. Solvation reduces binding energies and the discrimination between bases but maintains the overall pattern of binding. DFT and ab initio data on arene-base interactions in the absence of ruthenium show that stacking and hydrogen-bonding interactions play a significant role but cannot account for all of the energy difference between bases observed. Atoms-in-molecules analysis allows further decomposition of binding energies into contributions from covalent-binding, hydrogen-bonding, and pi-stacking interactions. Larger arenes undergo stabilizing stacking interactions, whereas N-H...X hydrogen bonding is independent of arene. Pairing of guanine to cytosine is affected by ruthenium complexation, with individual hydrogen-bonding energies being altered but the overall pairing energy remaining almost constant.     

How flexible are fleximer nucleobases? A computational study

Density functional theory was used to study the potential energy surface for rotation about the carbon-carbon bonds in a variety of guanosine, adenosine, and inosine fleximers, which are modified purines with the imidazole and pyrimidine rings separated by a single carbon-carbon bond. Various connectivities between C4 or C5 of the imidazole ring and C5' or C6' of the pyrimidine ring were considered. Calculations on fleximer nucleobases in the absence of the ribose moiety suggest that a planar relative arrangement of the imidazole and pyrimidine rings is favored, and that all fleximers are indeed very flexible with regards to rotation about the carbon-carbon bond, where calculated barriers are generally less than 40 kJ mol(-1). Furthermore, calculated binding energies of fleximer-pyrimidine pairs indicate that the hydrogen-bonding properties of these modified nucleobases mimic those of the corresponding natural purine. Inclusion of the sugar moiety often leads to a favored nonplanar orientation of the two rings, and either a reduction in the rotational barrier height or small changes in the rotational surface depending on the connectivity and nucleobase considered. It is concluded that several connectivities may have favorable properties for biochemical applications where flexible nucleobases would be beneficial.     

Thermochemistry and gas-phase ion energetics of 2-hydroxy-4-methoxy-benzophenone (oxybenzone)

We have investigated the thermochemistry and ion energetics of the oxybenzone (2-hydroxy-4-methoxy-benzophenone, C14H12O3, 1H) molecule. The following parameters have been determined for this species: gas-phase enthalpy for the of neutral molecule at 298.15K, (Delta(f)H0(m)(g) = -303.5 +/- 5.1 kJ x mol-1), the intrinsic (gas-phase) acidity (GA(1H) = 1402.1 +/- 8.4 kJ x mol-1), enthalpy of formation for the oxybenzone anion (Delta(f)H0(m)(1-,g) = -402.3 +/- 9.8 kJ x mol-1). We also have obtained the enthalpy of formation of, 4-hydroxy-4'-methoxybenzophenone (Delta(f)H0(m)(g) = -275.4 +/- 10 kJ x mol-1) and 3-methoxyphenol anion (Delta(f)H0(m)(C7H7O2-,g) = -317.7 +/- 8.7 kJ x mol-1). A reliable experimental estimation of enthalpy related to intramolecular hydrogen bonding in oxybenzone has also been obtained (30.1 +/- 6.3 kJ x mol-1) and compared with our theoretical calculations at the B3LYP/6-311++G** level of theory, by means of an isodesmic reaction scheme. In addition, heat capacities, temperature, and enthalpy of fusion have been determined for this molecule by differential scanning calorimetry.     

Coupling of complex aromatic ring vibrations to solvent through hydrogen bonds: effect of varied on-ring and off-ring hydrogen-bonding substitutions

In this study, we examine the coupling of a complex ring vibration to solvent through hydrogen-bonding interactions. We compare phenylalanine, tyrosine, l-dopa, dopamine, norepinephrine, epinephrine, and hydroxyl-dl-dopa, a group of physiologically important small molecules that vary by single differences in H-bonding substitution. By examination of the temperature dependence of infrared absorptions of these molecules, we show that complex, many-atom vibrations can be coupled to solvent through hydrogen bonds and that the extent of that coupling is dependent on the degree of both on- and off-ring H-bonding substitution. The coupling is seen as a temperature-dependent frequency shift in infrared spectra, but the determination of the physical origin of that shift is based on additional data from temperature-dependent optical experiments and ab initio calculations. The optical experiments show that these small molecules are most sensitive to their immediate H-bonding environment rather than to bulk solvent properties. Ab initio calculations demonstrate H-bond-mediated vibrational coupling for the system of interest and also show that the overall small molecule solvent dependence is determined by a complex interplay of specific interactions and bulk solvation characteristics. Our findings indicate that a full understanding of biomolecule vibrational properties must include consideration of explicit hydrogen-bonding interactions with the surrounding microenvironment.     

Kinetic investigations of the process of encapsulation of small hydrocarbons into a cavitand-porphyrin

Exchange of guest molecules into capsule shaped host molecules is the most fundamental process in host-guest chemistry. Several examples of quantitative measurements of guest exchange rates have been reported. However, there have been no reports on the activation energies of these processes. A molecule known as cavitand-porphyrin (H2CP) has been reported to have a flexible host structure capable of facilitating moderate guest exchange rates suitable for kinetic measurements of the guest exchange process with 1H NMR. In this article, various kinetic and thermodynamic parameters related to the process of encapsulation of small hydrocarbons into H2CP in CDCl3 solution were determined by 2D exchange spectroscopy (EXSY): association and dissociation rate constants (k(ass) = 320 M-1 s-1, k(diss) = 1.4 s-1 for methane at 25 degrees C), the corresponding activation energies (E(a,ass) = 27 kJ.mol-1, E(a,diss) = 58 kJ.mol-1), and thermodynamic parameters for each process (DeltaG++(ass) = 59 kJ.mol-1, DeltaG++(diss) = 72 kJ.mol-1, DeltaH++(ass) = 25 kJ.mol-1, DeltaH++(diss) = 55 kJ.mol-1, DeltaS++(ass) = -113 J.K-1.mol-1, and DeltaH++(diss) = 58 J.K-1.mol-1 for methane). The thermodynamic parameters (DeltaG degrees = -13 kJ.mol-1, DeltaH degrees = -31 kJ.mol-1, DeltaS degrees = -60 J.K-1.mol-1 for methane) for this encapsulation equilibrium determined by EXSY were comparable to those for methane determined by 1D 1H NMR titration (DeltaG degrees = -11 kJ.mol-1, DeltaH degrees = -33 kJ.mol-1, DeltaS degrees = -75 J.K-1.mol-1 for methane). In addition, the structure of the methane encapsulation process was revealed by ab initio MO calculations. The activation energies for methane association/dissociation were estimated from MP2 calculations (E(a,ass) = 58.3 kJ.mol-1, E(a,diss) = 89.1 kJ.mol-1, and DeltaH degrees = -30.8 kJ.mol-1). These values are in accord with the experimentally determined values. The observed guest exchange rates and energies are compared with the corresponding values of various reported capsule-shaped hosts.     

Restricting the conformational heterogeneity of RNA by specific incorporation of 8-bromoguanosine

In an effort to reduce the conformational heterogeneity of RNA, the modified nucleobase 8-bromoguanosine (8BrG) was introduced into oligonucleotides having the hairpin tetraloop motif YNMG (Y = U or C and M = C or A). Purine nucleobases with bromine at position eight are known to preferentially adopt the syn conformation as nucleosides. The hairpin tetraloop motif YNMG was chosen as a model system because it has a syn guanosine at position four of the loop that is essential for thermodynamic stability. Thermodynamic and structural characterization of modified oligonucleotides with the hairpin sequences UUCG, CGCG, and CGAG by UV-melting and NMR spectroscopy revealed that 8BrG substitution has a small effect upon the hairpin conformation, while the duplex conformation is strongly destabilized (DeltaDeltaG degrees 37 approximately +4.7 kcal mol-1), thus inhibiting dimerization. These results support a model in which 8BrG substitution shifts the hairpin-duplex equilibrium constant toward the hairpin conformation by destabilizing the duplex. This methodology should be useful for limiting conformational heterogeneity in large RNAs, with potential applications in structural biology and enzymology.     

Computational and experimental evidence for the structural preference of phenolic C-8 purine adducts

The structural and spectral properties of (ortho and para) C8-aryl-purine adducts formed from carbon attachment by phenolic toxins were investigated through DFT calculations and UV-vis absorbance and emission studies. The global minima of both the deoxyadenosine (dA) and deoxyguanosine (dG) adducts adopted a syn conformation about the glycosidic bond due to the presence of an O5'-H...N3 hydrogen bond, where the anti minima are 20-30 kJ mol-1 higher in energy. While the nucleobase adducts are planar, the presence of the deoxyribose sugar induces a twist about the carbon-carbon bond connecting the phenol and nucleobase rings. ortho-Phenolic adducts are less twisted than the corresponding para adducts due to stabilization provided by an intramolecular O-H...N7 bond. Solvation calculations, in combination with UV-vis studies, demonstrate that the structural preference is solvent dependent, where solvents with hydrogen-bonding abilities disrupt the intramolecular O-H...N7 hydrogen bond such that a greater degree of twist is observed, and less polar solvents stabilize the planar structure. Indeed, the ratio of twisted to planar conformers is estimated to be as large as 50:50 in some aprotic solvents. Thus, the combined experimental and computational approach has provided a greater understanding of the structure of the ortho- and para-dA and dG C-bonded phenoxyl adducts as the first step to understanding the biological consequences of this form of DNA damage.     

Specific and nonspecific metal ion-nucleotide interactions at aqueous/solid interfaces functionalized with adenine, thymine, guanine, and cytosine oligomers

This article reports nonlinear optical measurements that quantify, for the first time directly and without labels, how many Mg(2+) cations are bound to DNA 21-mers covalently linked to fused silica/water interfaces maintained at pH 7 and 10 mM NaCl, and what the thermodynamics are of these interactions. The overall interaction of Mg(2+) with adenine, thymine, guanine, and cytosine is found to involve -10.0 ± 0.3, -11.2 ± 0.3, -14.0 ± 0.4, and -14.9 ± 0.4 kJ/mol, and nonspecific interactions with the phosphate and sugar backbone are found to contribute -21.0 ± 0.6 kJ/mol for each Mg(2+) ion bound. The specific and nonspecific contributions to the interaction energy of Mg(2+) with oligonucleotide single strands is found to be additive, which suggests that within the uncertainty of these surface-specific experiments, the Mg(2+) ions are evenly distributed over the oligomers and not isolated to the most strongly binding nucleobase. The nucleobases adenine and thymine are found to bind only three Mg(2+) ions per 21-mer oligonucleotide, while the bases cytosine and guanine are found to bind eleven Mg(2+) ions per 21-mer oligonucleotide.     

Density functional study of the conformational space of 4C1 D-glucuronic acid

The conformational space of (4)C(1) alpha- and beta-d-glucuronic acid was scanned by HF/3-21G(p) calculations followed by optimization of the 15 most stable structures for each, using the B3LYP density functional theory method in conjunction with a diffuse polarized valence triple-zeta basis set. We found a general preference of the alpha anomers in the isolated molecules in agreement with the large endo-anomeric hyperconjugation effects in these structures. From the other intramolecular interactions (exo-anomeric hyperconjugation, hydrogen-bonding, dipole-dipole, and steric interactions), the effect of the hydrogen bonding is the most pronounced and plays a major role in determining the stability order within the alpha and beta series. The most stable conformer of both alpha and beta (4)C(1) d-glucuronic acid is the structure with the maximum number (5) of intramolecular hydrogen bonds. Introduction of solvent (water) effects by the SCI-PCM model resulted in two characteristic changes of the energetic properties: the gas-phase stability order changed considerably, and the energy range of the 15 most stable conformers decreased from 30 to 15 kJ/mol. The geometrical parameters reflect well the superimposed effects of hyperconjugation and hydrogen-bonding interactions. Most characteristics are the variations of the C-O bond distances (within a range of 0.04 A) upon the combined intramolecular effects.     

Metal fluorides form strong hydrogen bonds and halogen bonds: measuring interaction enthalpies and entropies in solution

The organometallic compound trans-(tetrafluoropyrid-2-yl)bis(triethylphosphine)-fluoronickel(II) (NiF) is shown to serve as a strong hydrogen bond and halogen bond acceptor in solution via intermolecular interactions with the fluoride ligand. The nature of the interactions has been confirmed by multinuclear NMR spectroscopy. Experimental binding constants, enthalpies, and entropies of interaction with hydrogen-bond-donor indole and halogen-bond-donor iodopentafluorobenzene have been determined by 19F NMR titration. In toluene-d8 solution indole forms a 1:1 and 2:1 complex with NiF (K1 = 57.9(3), K2 = 0.58(4)). Interaction enthalpies and entropies are -23.4(2) kJ mol-1 and -44.5(8) J mol-1 K-1, respectively, for the 1:1 complex; -14.8(8) kJ mol-1 and -53(3) J mol-1 K-1, respectively, for the 2:1 complex. In toluene-d8 solution iodopentafluorobenzene forms only a 1:1 complex (K1 = 3.41(9)) with enthalpy and entropy of interaction of -16(1) kJ mol-1 and -42(4) J mol-1 K-1, respectively. A marked solvent effect was observed for the halogen bond interaction. NMR titrations in heptane solution indicated formation of both 1:1 and 2:1 complexes of iodopentafluorobenzene with NiF (K1 = 21.8(2), K2 = 0.22(4)). Interaction enthalpies and entropies are -26(1) kJ mol-1 and -63(4) J mol-1 K-1, respectively, for the 1:1 complex; -21(1) kJ mol-1 and -83(5) J mol-1 K-1, respectively, for the 2:1 complex. There is a paucity of such experimental energetic data particularly for halogen bonds despite substantial structural data. These measurements demonstrate that halogen bonds are competitive with hydrogen bonds as intermolecular interactions and provide a suitable benchmark for theoretical calculations and quantitative input into design efforts in supramolecular chemistry and crystal engineering.     

Molecular recognition in cyclodextrin complexes of amino acid derivatives. 1. Crystallographic studies of beta-cyclodextrin complexes with N-acetyl-L-phenylalanine methyl ester and N-acetyl-L-phenylalanine amide pseudopeptides

Cyclodextrins (CDs) are widely utilized in studies of chiral and molecular recognition. By changing the functionality of the guest molecule, the effect of such changes on recognition by the host CD molecule can be examined. We report crystal structure determinations for two nearly isomorphous complexes of phenylalanine derivatives: beta-CD/N-acetyl-L-phenylalanine methyl ester and beta-CD/N-acetyl-L-phenylalanine amide. The complexes crystallize as hydrated head-to-head host dimers with two included guest molecules in space group P1. The crystal packing is such that it presents a nonconstraining hydrophobic pocket adjacent to a hydrophilic region, where potential hydrogen-bonding interactions with hydroxyl groups of neighboring cyclodextrin molecules and waters of hydration can occur. The two host molecules display very similar conformations; only a few of the primary hydroxyl groups are conformationally disordered. There are a number of changes in the location of water of hydration molecules, some of which are the result of different hydrogen-bonding interactions. For the different guest molecules, similar modes of penetration are observed in the CD torus; however, there is a 0.985-A shift in the position of the guest molecules in the host torus, which takes place without changing the hydrophobic interactions displayed by the phenyl side chains. This observation and the thermal motion of the guest molecules in the ester complex are taken as evidence that complex binding forces are weak. The pseudopeptides experience a significant degree of flexibility in the crystalline environment provided by CD dimers. Conformational differences of the pseudopeptide backbones and the presence of disordered water molecules in the host-guest interface provide examples of different hydrogen-bonding schemes of similar potential energy. The crystal system presents an opportunity to establish a database of molecular interactions for small peptides and peptide analogues with waters of hydration and functional groups in nonconstraining binding environments.     

An application of the van der Waals density functional: Hydrogen bonding and stacking interactions between nucleobases

We apply the van der Waals density functional (vdW-DF) to study hydrogen bonding and stacking interactions between nucleobases. The excellent agreement of our results with high level quantum chemical calculations highlights the value of the vdW-DF for first-principles investigations of biologically important molecules. Our results suggest that, in the case of hydrogen-bonded nucleobase pairs, dispersion interactions reduce the cost of propeller twists while having a negligible effect on buckling. Furthermore, the efficient scaling of DFT methods allowed for the easy optimization of separation distance between nucleobase stacks, indicating enhancements in the interaction energy of up to 3 kcalmol over previous fixed distance calculations. We anticipate that these results are significant for extending the vdW-DF method to model larger vdW complexes and biological molecules.     

Interaction of dihydrogen with small and light molecules

Second-order M?ller-Plesset (MP2) calculations (using the approximate resolution of the identity, RI-MP2), explicitly correlated MP2 (MP2-R12) calculations, and coupled-cluster calculations including all single and double excitations with a perturbative estimate of triple excitations [CCSD(T)] are performed to study the interaction of molecular hydrogen with the small molecules HF, H2O, NH3, and LiOH. Different adsorption positions are studied. In the cases of H2O and NH3, the most favorable configuration places H2 in an end-on fashion on the O or N atom, respectively. In the cases of HF and LiOH, the H2 molecule takes a side-on position on the H atom of HF or the Li atom. With respect to MP2 calculations in a triple-zeta basis, both the enlargement of the basis set and the extension of the correlation treatment (CCSD(T) vs MP2) increase the interaction energy. The basis set limit CCSD(T) estimates of the interaction energy of H2 with the HF, H2O, NH3, and LiOH molecules amount to 4.40, 2.67, 3.02, and 10.74 kJ mol-1, respectively. The interaction energy for the simultaneous interaction of H2 with two LiOH molecules does not significantly exceed the value obtained for the interaction with a single LiOH molecule. Furthermore, the interaction energies (by MP2) of H2 with glycine, the glycine dimer, and imidazolium chloride amount to 2.78, 5.00, and 6.30 kJ mol-1, respectively.