The structure and energetics of the ring isomers of C(4n+2) (n=3-5) carbon clusters were studied by using coupled-cluster singles and doubles excitation theory to overcome the vast differences existing in the literature. The results obtained in the present study clearly indicate that C(14), C(18), and C(22) carbon rings have bond-length and bond-angle alternated acetylenic minimum energy structures. Contrarily, density functional theory calculations were unable to predict these acetylenic-type structures and they ended up with the cumulenic structures. It is found from the coupled-cluster studies that the lowest-energy ring isomer for the first two members of C(4n+2) series is a bond-angle alternated cumulenic D((2n+1)h) symmetry structure while the same for the remaining members is a bond-length and bond-angle alternated C((2n+1)h) symmetry structure. In C(4n+2) carbon rings, Peierls-type distortion, transformation from bond-angle alternated to bond-length alternated minimum energy structures, occurs at C(14) carbon ring.

The structure and torsional barriers at 0° and 90° for biphenyl were studied by both ab initio and density functional methods by using various levels of theory with different basis sets. The torsional angle (φ) calculated at the MP2/6-311+G(2d,2p) level was 42.1°, while φ calculated using various density functionals with different basis sets was close to 40°. In contrast with the ab initio results, the torsional barrier at 0° [ΔE0=E(φ=0°)−E(equilibrium)] obtained using various density functionals coincided well with experimental values. The torsional barrier ratio (ΔE90/ΔE0) obtained at the B3LYP/cc-pVTZ level, 1.0988, agreed well with the experimental value, 1.0833, whereas it was 0.416 at the MP2/6-311G(d,p) level. Structural studies on biphenyl ions showed that the biphenyl cation has a nonplanar (φ=19°) structure whereas its anionic counterpart has a planar structure. The ionization potential obtained at the B3LYP/6-311+G(2d,2p) level was 7.86 eV. Contrary to an earlier study, a positive electron affinity (EA) was obtained, in accordance with experimental predictions. EA values of 0.021 and 0.076 eV were obtained at the B3LYP/6-311+G(2d,2p) and B3LYP/aug-cc-pVDZ levels, respectively.

Dipeptidyl peptidase IV (DPP-4) enzyme is responsible for the degradation of incretins that stimulates insulin secretion and hence inhibition of DPP-4 becomes an established approach for the treatment of type 2 diabetics. We studied the interaction between DPP-4 and its inhibitor drugs (sitagliptin 1, linagliptin 2, alogliptin 3, and teneligliptin 4) quantitatively by using fragment molecular orbital calculations at the RI-MP2/cc-pVDZ level to analyze the inhibitory activities of the drugs. Apart from having common interactions with key residues, inhibitors encompassing the DPP-4 active site extensively interact widely with the hydrophobic pocket by their hydrophobic inhibitor moieties. The cumulative hydrophobic interaction becomes stronger for these inhibitors and hence linagliptin and teneligliptin have larger interaction energies, and consequently higher inhibitory activities, than their alogliptin and sitagliptin counterparts. Though effective interaction for both 2 and 3 is at subsite, 2 has a stronger binding to this subsite interacting with Trp629 and Tyr547 than 3 does. The presence of triazolopiperazine and piperazine moiety in 1 and 4, respectively, provides the interaction to the S2 extensive subsite; however, the latter’s superior inhibitory activity is not only due to a relatively tighter binding to the S2 extensive subsite, but also due to the interactions to the S1 subsite. The calculated hydrophobic interfragment interaction energies correlate well with the experimental binding affinities (KD) and inhibitory activities (IC50) of the DPP-4 inhibitors.

The protonation state of the deazaflavin dependent nitroreductase (Ddn) enzyme bound cofactor F420 was investigated using UV-visible spectroscopy and computational simulations. The reduced cofactor F420H2 was determined to be present in its deprotonated state in the holoenzyme form. The mechanistic implications of these findings are discussed.