Ab initio calculations have been performed on a series of complexes formed between halogen-containing molecules and ammonia to gain a deeper insight into the nature of halogen bonding. It appears that the dihalogen molecules form the strongest halogen-bonded complexes with ammonia, followed by HOX; the charge-transfer-type contribution has been demonstrated to dominate the halogen bonding in these complexes. For the complexes involving carbon-bound halogen molecules, our calculations clearly indicate that electrostatic interactions are mainly responsible for their binding energies. Whereas the halogen-bond strength is significantly enhanced by progressive fluorine substitution, the substitution of a hydrogen atom by a methyl group in the CH(3)X...NH(3) complex weakened the halogen bonding. Moreover, remote substituent effects have also been noted in the complexes of halobenzenes with different para substituents. The influence of the hybridization state of the carbon atom bonded to the halogen atom has also been examined and the results reveal that halogen-bond strengths decrease in the order HC triple bond CX > H(2)C=CHX approximately O=CHX approximately C(6)H(5)X > CH(3)X. In addition, several excellent linear correlations have been established between the interaction energies and both the amount of charge transfer and the electrostatic potentials corresponding to an electron density of 0.002 au along the R-X axis; these correlations provide good models with which to evaluate the electron-accepting abilities of the covalently bonded halogen atoms. Finally, some positively charged halogen-bonded systems have been investigated and the effect of the charge has been discussed.

No abstract

Correlations between interaction energies and various structural parameters were established to reveal the differences between hydrogen bonds and halogen bonds.

General rights Copyright for the publications made accessible via the Queen's University Belfast Research Portal is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights.

No abstract

No abstract

These two models provide useful information to guide drug design strategies aimed at obtaining potent and selective CDK4 inhibitors.

In microorganisms and plants, NAGK N-acetyl-L-glutamate kinase (NAGK) catalyses the second step in L-arginine synthesis, the phosphorylation of N-Acetyl-L-glutamate (NAG) to give N-acetyl-L-glutamate-5-phosphate (NAGP). NAGK is only present in microorganisms and plants but absent from mammals, which makes it an attractive target for antimicrobial or biocidal development. Understanding the substrate binding mode and reaction mechanism of NAGK is crucial for targeting the kinase to develop potential therapies. Here the substrate binding mode was studied by comparing the conformational change of NAGK in the presence and in the absence of the NAG substrate based on molecular dynamic simulations. We revealed that with substrate binding the catalytic site of the kinase involving three loops in NAGK exhibits a closed conformation, which is predominantly controlled by an interaction between Arg98 and the α-COOof NAG. Lys41 is found to guide phosphate transfer through the interactions with the β-,γ-, and γ-phosphate oxygen atoms of ATP surrounded by two highly conserved glycine residues (Gly44 and Gly76), while Arg98 helps to position the NAG substrate in the catalytic site, which facilitate the phosphate transfer. Furthermore, we elucidated phosphate transfer reaction mechanism using hybrid density functional theory-based QM/MM calculations (B97D/AMBER99) and found that the catalysis follows a dissociative mechanism.