Structure and Stability of the Hexamer Clusters of Glycine and L-Alanine: A DFT and DLPNO–CCSD(T) Study

The structure and stability of hexamer clusters of glycine (Gly)₆ and l-alanine (Ala)₆ were examined using the density functional theory (DFT) method M05-2X. Single-point energy calculations were performed using the DFT-M06-2X and DLPNO-CCSD(T) methods. Different feasible structures of the neutral hexamer, such as the linear (<b>LI</b>), cyclic (<b>CY</b>), and coiled (<b>CO</b>, <b>HE1</b>, and <b>HE2</b>) arrangements, were generated and subjected to complete structural optimization at the M05-2<i>X</i>/6-311++G(d,p) level. A cyclic zwitterionic structure (<b>ZI</b>) was also studied. The optimized geometries were found to be stabilized through different modes of HBs OH···NH, CO···HN, HO···HN, CO···HC, and OH···OH. Study at the M06-2X/def2-QZVP//M05-2<i>X</i>/6-311++G(d,p) level reveals that in (Ala)₆ the binding energies (BEs) of <b>HE1</b>, <b>HE2</b>, and <b>ZI</b> are in the range -76 to -77 kcal/mol. The BEs vary within 1 kcal/mol, which indicates that the hexamer can coexist in the above structures. The BEs of (Gly)₆ in the above structures are, respectively, -74.6, -73.0, and -72.5 kcal/mol. The dispersion interaction energy in the low-lying structures is <10% of the total BEs. Analysis of the various modes of HB interactions reveals that the OH···NH HBs exhibit short lengths of <1.75 Å in the neutral clusters. There is significant overlap of the donor and acceptor orbitals, leading to covalent interactions. The covalent character of the OH···NH HB is defined using the Wiberg bond order in the natural bond orbital (NBO) basis. It is observed that the OH···NH HBs are indeed weak covalent bonds, having covalent character in the range 12.9-24.7%. The covalent bonding is negligible in the remaining HB types operating in the cluster due to longer HB lengths of ≥1.98 Å. The enhanced covalent character of OH···NH in the cyclic and coiled structures relative to the linear structure, explains the higher stability in <b>CY</b>, <b>HE1</b>, and <b>HE2</b>. The DLPNO-CCSD(T)/cc-pVTZ-predicted BEs are in the ranges of -48 to -55 kcal/mol in (Gly)₆ and -51 to -59 kcal/mol in (Ala)₆. It is likely that the above binding energies are underestimated due to a large basis set superposition error (BSSE). Test calculations on the <b>LI</b> structure at the DLPNO-CCSD(T)/aug-cc-pVTZ level decreased the BSSE.