RESUMEN

Xerantholide is a sesquiterpene lactone that has anti-gonorrhea and anti-plasmodium activities. We present gas-phase electronic structure calculations of the equilibrium geometry of xerantholide, its adiabatic electron affinity (AEA), adiabatic ionization energy (AIE) and the energy barrier (ΔE‡) connecting the lowest energy conformers of the sesquiterpene. The computations were performed with the B3LYP, M06-2X and ωB97xd variants of the density functional theory (DFT) in conjunction with large basis sets. With the inclusion of the vibrational zero point energy, the computed AEA range from 0.740 eV [B3LYP/Aug-CC-pVTZ] to 0.774 eV [B3LYP/6-311++G(d,p)], and the AIE is roughly 8.6 eV at all theoretical levels. At the B3LYP/Aug-CC-pVTZ level, the barrier (ΔE‡) connecting the two lowest energy conformers is predicted to be 13.9 kcal/mol. Based on the molecular docking analysis, xerantholide interacts with the active site of Neisseria gonorrhoeae carbonic anhydrase (NgCA) via hydrogen bonding, metal-acceptor interaction, and non-polar alkyl and pi-alkyl interactions. The predicted binding affinity of - 6.8 kcal/mol compares well with those obtained for standard NgCA inhibitors such as acetazolamide (-5.7 kcal/mol). A biomimetic model study involving xerantholide and zinc-tris imidazole ([ZnIm3]2+) ion was also carried out at different theoretical levels to estimate the interaction energy for the formation of the complex formed between the ligand and the active site model of NgCA. The binding free energy (ΔG) has been calculated to be - 28.5 kcal/mol at the B3LYP/6-311++G(d,p) level. The interaction mode observed in both the docking and the model calculations involves the lactone ring.

Asunto(s)

Anhidrasas Carbónicas , Neisseria gonorrhoeae , Simulación del Acoplamiento Molecular , Enlace de Hidrógeno , Lactonas

RESUMEN

We present a systematic theoretical study on mono and digallium selenide clusters, Ga(m)Se(n) (m = 1, 2 and n = 1-4), along with their negatively and positively charged counterparts. Different theoretical methods, namely density functional theory (DFT), second-order Møller-Plesset perturbation theory (MP2) and coupled cluster singles and doubles, including non-iterative triples [CCSD(T)], were employed in conjunction with the 6-311+G(2df) basis set. The lowest-energy configurations of gallium selenides prefer to be planar, with the exception of cationic GaSe4 and Ga2Se4. The adiabatic electron affinities (AEA) of Ga(m)Se(n) (m = 1, 2 and n = 1-4) clusters range from 1.07 to 3.78 eV, and their adiabatic ionization potentials (AIP) vary from 7.57 to 8.76 eV using the CCSD(T)//B3LYP level of theory. It was found that the AEAs of gallium selenides do not depend solely on the electrophilicity of the clusters but also on their electronic structures. No significant trend was observed in the AIP values and HOMO-LUMO (H-L) gaps with increase in cluster size of the mono and digallium selenide series. Among the dissociation channels, the decomposition of GaSe4 → GaSe2 + Se2 was found to be thermodynamically most favored. Furthermore, the AEAs of GaSe2, GaSe3, GaSe4 and Ga2Se4 were found to exceed that of the chlorine atom and are therefore termed as 'superhalogens'. Finally, the AEAs of the Ga2X(n) (X = O-Se; n = 2-4) series were found to be almost similar.

RESUMEN

The photoionization of (pro)(n)DHB (pro = proline, DHB = 2,5-dihydroxybenzoic acid, n = 0, 1, 2 or 4) clusters was studied both experimentally and computationally. Experimentally the (pro)(n)DHB clusters are generated in the gas phase by laser desorption and supersonic jet entrainment. The photoionization thresholds are then determined by the mass-selective measurement of both one- and two-color photoionization efficiency curves. These experiments demonstrate that the ionization energies (IEs) of the (pro)(n)DHB clusters are substantially reduced in comparison with the IE of free DHB. Computational studies of the (pro)(n)DHB clusters provide insights into the mechanism of IE reduction. For the (pro)DHB system the IE reduction results from spin delocalization in the ion state of the cluster. In contrast, for the (pro)(2)DHB and (pro)(4)DHB clusters the IE reduction results from an inductive delocalization of electron density from pro to DHB in the ground state of the cluster. This latter effect, which is a result of the specific hydrogen-bonding interactions occurring in the mixed clusters, leads to IE reductions of >1 eV. Finally, determination of the energetics of the (pro)(2)DHB radical cation demonstrate that the DHB-to-proline proton transfer reaction is a barrierless, exoergic process in the ion state and that energetic demands for cluster dissociation to protonated (pro)(2) plus a deprotonated DHB radical are substantially lower than those for cluster dissociation to (pro)(2) plus DHB(+*). Cumulatively, these studies provide new energetic and mechanistic insights into both primary and secondary MALDI ionization processes.