Alkyl Spacer Length and Protonation Induced Changes in Crystalline Psychoactive Arylpiperazine Derivatives: Single-Crystal X-ray, Solid-State NMR, and Computational Studies

作者：Pindelska Edyta^*; Madura Izabela D; Szeleszczuk Lukasz; Zeszko Anna; Jaskowska Jolanta; Marek Paulina H; Kolodziejski Waclaw

来源：Crystal Growth & Design, 2016, 16(11): 6371-6380.

DOI：10.1021/acs.cgd.6b00993

A series of new long-chain arylpiperazine derivatives with a flexible alkyl spacer were synthesized. A controversy concerning the role of the spacer, whether it participates actively in binding to 5-HT1A and D-2 receptors or it acts as a distance arm) encouraged us to investigate how the molecular and crystal structure changes with the increased length of the alkyl linker (from four CH2 units to six). In this study both the basic active compounds as well as their hydrochlorides were-studied. Single crystal X-ray structure analysis with a combination of C-13, N-15 solid state NMR. spectroscopy supported,by gauge-including projector-augmented wave calculations of chemical shielding was :used.. These studies were aimed to examine, elucidate, and compare molecular conformations and to point out the most important intermolecular interactions leading to large supramolecular synthons formed in crystals of both bases and hydrochlorides.

• 出版日期2016-11