Boča Roman, Štofko Juraj, Rajnák Cyril
Faculty of Health Science, University of Ss. Cyril and Methodius, 91701 Trnava, Slovakia.
Faculty of Natural Science, University of Ss. Cyril and Methodius, 91701 Trnava, Slovakia.
ACS Omega. 2025 Aug 15;10(33):37383-37397. doi: 10.1021/acsomega.5c03078. eCollection 2025 Aug 26.
Small molecules containing phenyl and aliphatic amine groups belonging to psychotropic drugs were studied by quantum chemical computational methods. Each of the 9 studied species (phenethylamine, amphetamine, ephedrine, pseudoephedrine, methamphetamine, MDMA, MDEA, MDA, MDAI) was considered in three oxidation states: neutral molecule, molecular cation, and molecular anion. Protonated residues from the hydrochloride forms were also considered. This allows, after full geometry optimization followed by vibrational analysis, the evaluation of global adiabatic electronic properties such as ionization energy, electron affinity, molecular electronegativity, chemical hardness, electrophilicity index, and absolute oxidation and reduction potentials. The ground-state molecular properties include electrical properties (atomic charges, dipole moment, quadrupole moment, and dipole polarizability), atomic spin densities, magnetic properties (NMR shielding constants), molar-mass-dependent molecular properties (solvated surface area and molecular volume), and thermodynamic properties (zero-point vibrational energy, entropic contribution, and Gibbs energy). Several correlations were found between molecular descriptors, e.g., molar-mass-dependent properties (dipole polarizability and zero-point vibration energy) vs molar mass, absolute oxidation potential vs adiabatic ionization energy, absolute reduction potential vs electrophilicity index, and C NMR shielding constants vs atomic charges. Electron subtraction upon ionization was monitored by inspection of local atomic characteristics, such as C NMR shielding constants and spin densities for the molecular cation. All calculations were done consistently with two quantum chemical methods in the extended basis set: B3LYP hybrid variant of Density Functional Theory and the post-Hartree-Fock method DLPNO-CCSD-(T), which includes the majority of the electron correlation energy. All calculations were done in water as a solvent. The number of studied systems is 108, i.e., 9 (molecules) × 2 (forms) × 3 (oxidation states) × 2 (methods).
采用量子化学计算方法研究了属于精神药物的含苯基和脂肪族胺基的小分子。所研究的9种物质（苯乙胺、安非他明、麻黄碱、伪麻黄碱、甲基苯丙胺、摇头丸、亚甲二氧乙基安非他明、甲撑二氧苯丙胺、甲撑二氧苯异丙胺）中的每一种都考虑了三种氧化态：中性分子、分子阳离子和分子阴离子。还考虑了盐酸盐形式的质子化残基。这使得在进行完全几何优化并随后进行振动分析之后，可以评估全局绝热电子性质，如电离能、电子亲和能、分子电负性、化学硬度、亲电性指数以及绝对氧化和还原电位。基态分子性质包括电学性质（原子电荷、偶极矩、四极矩和偶极极化率）、原子自旋密度、磁学性质（核磁共振屏蔽常数）、与摩尔质量相关的分子性质（溶剂化表面积和分子体积）以及热力学性质（零点振动能、熵贡献和吉布斯自由能）。在分子描述符之间发现了几种相关性，例如，与摩尔质量相关的性质（偶极极化率和零点振动能）与摩尔质量、绝对氧化电位与绝热电离能、绝对还原电位与亲电性指数以及碳核磁共振屏蔽常数与原子电荷之间的相关性。通过检查局部原子特征，如分子阳离子的碳核磁共振屏蔽常数和自旋密度，监测电离时的电子减法。所有计算均使用扩展基组中的两种量子化学方法一致进行：密度泛函理论的B3LYP混合变体和后哈特里 - 福克方法DLPNO - CCSD - (T)，其中包括大部分电子相关能。所有计算均在水作为溶剂的条件下进行。所研究的系统数量为108，即9（分子）×2（形式）×3（氧化态）×2（方法）。
