A DFT-driven Analysis of Aggregation-Dependent Stability in Alkylpyrazines: Monomers, Dimers, and Beyond

Precisely determining the structure and properties of analytes and their ions, such as proton-bound clusters, holds significant importance in both the theoretical understanding and practical applications of mass spectrometry, ion mobility spectrometry, and other related chemical ionization methods. Density functional theory (DFT) calculations were utilized to investigate the conformational constraints governing the formation of stable proton-bound clusters of alkyl pyrazines, encompassing monomers, dimers, and trimers. Employing the B3LYP/6-31+G(d, p) method with D3 dispersion correction, molecular properties, including electric dipole moment, polarizability, and proton affinity, were presented and compared with results from higher basis sets like Aug-cc-PVTZ, demonstrating the efficiency of the chosen approach. Natural bond orbital (NBO) calculations provided insights into natural charges, charge transfer, and stability of proton-bound dimer and trimer structures, revealing a decrease in stability from monomers to trimers. Notably, protonated trimers exhibited stacked structures instead of expected protonated forms, aligning with experimental observations. The stability of alkyl pyrazine clusters was found to be influenced by various factors, including structure, electric dipole moment, polarizability, charge transfer, and steric hindrance. Additionally, proton affinity calculations indicated a linear relationship between stability and proton affinity in monomers, with constant dissociation energies observed in proton-bound dimers regardless of proton affinity variations. The study provides comprehensive insights into the stability paradigm of alkyl pyrazines, facilitating a deeper understanding of their behavior across different structural configurations and molecular concentrations.