Amino and cyano N atoms in competitive situations: which is the best hydrogen-bond acceptor? A crystallographic database investigation.

The relative hydrogen-bond acceptor abilities of amino and cyano N atoms have been investigated using data retrieved from the Cambridge Structural Database and via ab initio molecular orbital calculations. Surveys of the CSD for hydrogen bonds between HX (X = N, O) donors, N-T-C identical with N (push-pull nitriles) and N-(Csp(3))(n)-C identical with N molecular fragments show that the hydrogen bonds are more abundant on the nitrile than on the amino nitrogen. In the push-pull family, in which T is a transmitter of resonance effects, the hydrogen-bonding ability of the cyano nitrogen is increased by conjugative interactions between the lone pair of the amino substituent and the C identical with N group: a clear example of resonance-assisted hydrogen bonding. The strength of the hydrogen-bonds on the cyano nitrogen in this family follows the experimental order of hydrogen-bond basicity, as observed in solution through the pK(HB) scale. The number of hydrogen bonds established on the amino nitrogen is greater for aliphatic aminonitriles N-(Csp(3))(n)-C identical with N, but remains low. This behaviour reflects the greater sensitivity of the amino nitrogen to steric hindrance and the electron-withdrawing inductive effect compared with the cyano nitrogen. Ab initio molecular orbital calculations (B3LYP/6-31+G** level) of electrostatic potentials on the molecular surface around each nitrogen confirm the experimental observations.

Computer modelling of sulfated carbohydrates: applications to carrageenans.

In this study, X-ray crystallographic data of sulfated monosaccharides have been used to derive appropriate parameters for sulfate groups in the Tripos force field, previously parameterized for carbohydrates. A database of nine sulfated monosaccharides occurring as building blocks of sulfated polysaccharides such as carrageenans and sulfated glycosaminoglycans has been built. These tools have then been used to evaluate the conformational energies of the repeating units of the kappa-, iota- and lambda-carrageenan polymers, taking into account the rotation around the sulfate groups. In a third step, helical conformations of carrageenans have been explored and the results compared with the experimental data obtained by X-ray fibre diffraction. Stable, single, right-handed helices, with geometric and helical parameters in close correspondence with the best models derived from X-ray diffraction data, have been generated. Finally, the configurational statistics of random-coil carrageenan chains have been investigated and compared with experimental data currently available on these polymers. A highly flexible character is predicted for kappa- and iota-carrageenans, with lambda-carrageenan showing slightly more extension.

Common ring motifs in proteins involving asparagine or glutamine amide groups hydrogen-bonded to main-chain atoms.

We report the frequent occurrence in proteins of motifs consisting of either 9-membered or 11-membered rings that involve the side-chain amide groups of asparagine and glutamine residues. The syn CO and NH groups of these amide groups are hydrogen-bonded to the main-chain NH and CO groups of other amino acid residues. The main-chain part of both the 9-membered and 11-membered rings has the conformation of a beta-strand. One such ring motifs occurs, on average, in half of all the proteins we examined. Similar conformations are found for most examples of the 9-membered and 11-membered rings. One of the 11-membered rings is distinct, compared to the others, in that its main-chain part has a mirror-image conformation. Another of the 11-membered rings occurs at the interior of the variable domains of some antibodies and assists in linking the two beta-sheets. We observe one 9-membered ring structure in a dihydrofolate reductase complex in which the amide in the nicotinamide group of the ligand NADP is bound to the enzyme. Groups that can form hydrogen bonds in a similar way to amide groups occur in several nucleotide bases; we find one example of a 9-membered ring involving adenine and main-chain atoms in the FAD-protein complex of glutathione reductase. Both have conformations like those of the other 9-membered rings.