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Quantum chemical DFT-B3LYP/6-31G* method and IR spectrometry have been used to investigate the natural and binding structures of Huperzine B (HupB) in order to better understand the interaction nature between acetylcholinesterase (AChE) and its inhibitor, with the view of designing new AChE inhibitors. The predicted and experimental results reveal that both the natural state and binding form of HupB adopt the chair conformation. Furthermore, the B3LYP/6-31G* results suggest that structure S1 should be the dominant form of the two possible chair structures (S1 and S2, Fig. 2). The calculated results also show that the condensed ring structure composing of rings A, B and C is very rigid. Therefore, its flexibility does not need to be considered when we try to dock this structure to its target. Indeed, this supposition is confirmed by the excellent alignment of the binding structure produced from our recent/break X-ray crystallographic structure of the HupB-AChE complex with the B3LYP/6-31G* predicted geometry. Among all the 111 predicted vibrational bands, the mode 110, which is resulted from the stretching of the bond N2–H and having the second highest frequency, is essential for the geometrical identification. The difference between our predicted strongest absorption band and experimental IR spectrum suggests that a strong intermolecular interaction, which could be a hydrogen bond, exists in HupB crystal. The electrostatic potential surface of HupB derived from our B3LYP/6-31G* CHelpG atomic charge suggests a mechanism of how HupB would interact with its target. In addition, the good agreement between predicted vibrational bands (scaled by a factor of 0.96) and experimental result shows that B3LYP/6-31G* is a good tool for studying such kind of natural compound.

The theoretical investigation of tetramethylammonium (TMA)−imidazole and TMA−furan complexes has been performed to justify the preferred structure of the cation−aromatic complexes predicated by the...

A detailed theoretical investigation of the tetramethylammonium(TMA)-benzene and TMA-pyrrole complexes has been performed to obtain the interaction properties of TMA with aromatics. Diffuse functions have been found to be important in the computational studies of these noncovalent complexes. Adding diffuse functions to the basis set decreases the binding energy by about 10% for the TMA-aromatic systems. Dispersion interactions in the TMA-aromatic systems are very important. They enhance the binding interactions between the TMA and the aromatic ring systems by about 0.5 kcal·mol-1 per interacting atomic pair, which is in agreement with the estimates of Rappe and Bernstein.1 Also, for the TMA-pyrrole complex, the presence of the dispersion interaction leads to a dramatic change in the optimized structure. Because B3LYP cannot handle properly the dispersion in the calculation, use of the Moller−Plesset second-order perturbation or other sophisticated methods should be considered in computational studies of c...

DFT/B3LYP calculations were carried out on complexes formed by NH4+ with aromatics, viz. benzene, phenol, pyrrole, imidazole, pyridine, indole, furane, and thiophene, to characterize the forces involved in such interactions and to gain further insight into the nature and diversity of cation−aromatic interactions. Such calculations may provide valuable information for understanding molecular recognition in biological systems and for force-field development. B3LYP/6-31G** optimization on 35 initial structures resulted in 11 different finally optimized geometries, which could be divided into three types: NH4+−π complexes, protonated heterocyclic−NH3 hydrogen bond complexes, and heterocyclic−NH4+ hydrogen bond complexes. For NH4+−π complexes, NH4+ always tilts toward the carbon−carbon bond rather than toward the heteroatom or the carbon−heteroatom bond. The calculated CHelpG charges suggest that the charge distribution of a free heterocyclic may be used to predict the geometry of its complex. Charge populati...