Significance Of Hydrogen Bonds Research Articles

Crystallographic analysis, Hirshfeld surface investigation, and DFT calculations of 2-phenoxy-triazoloquinazoline molecule: Implications for drug design

This study presents a comprehensive structural and computational investigation of 2-phenoxy-1,2,4-triazolo[1,5-a]quinazoline (PTQ), a compound with promising pharmacological potential. Single-crystal X-ray diffraction (SCXRD) analysis revealed the molecular geometry and crystal packing, while density functional theory (DFT) calculations provided insights into electronic properties and reactivity. Hirshfeld surface analysis elucidated intermolecular interactions, highlighting hydrogen bonding, van der Waals forces, and π–π stacking as crucial factors in crystal stability. Fingerprint analysis quantified these interactions, revealing the dominance of hydrogen contacts and the significance of hydrogen bonds and C–H···π interactions. Void analysis identified potential areas for inclusion complex formation. Frontier molecular orbital analysis and molecular electrostatic potential (MEP) mapping identified potential electrophilic and nucleophilic sites, guiding future reactivity studies. Furthermore, in silico ADMET and molecular docking studies were performed to assess the drug-likeness and potential antihistamine activity of PTQ.

The Role of Side-chain Hydrogen Bonds in the Formation and Stabilization of Secondary Structure in Soluble Proteins

Intra-molecular side-chain:main-chain (sch:mch) and side-chain (sch:sch) hydrogen bonds observed in 44 well refined crystallographic protein structures with non-homologous sequences have been identified, classified and analysed to detect recurring structural patterns. Each observed bond was characterized by the position of its acceptor and donor groups relative to the N and C termini of the particular secondary structure in which they occur and according to their appearance within the same of sequentially separated secondary structures. The role of short-range hydrogen bonds in the formation and stabilization of a secondary structure and the importance of long-range hydrogen bonds as a cohesive force for different structural segments were also examined. It was found that the N terminus of α-helices is characterized by recurring sch:mch and sch:sch bonds with elements of the preceding coil segment, while at the C terminus a frequent intra-helix sch:mch hydrogen bond was frequently observed. The residues at or near the β-strand termini often cross-linked, through hydrogen-bonding, non-sequential coil segments. Coil structures were characterized by recurring, internal sch:mch hydrogen bonding involving small polar side-chain groups situated at or near their N termini (coil N-capping). The significance of hydrogen bonds as formers and stabilizers of a protein fold and the association of its secondary structural units was also considered through an examination of bond density and distribution throughout the protein tertiary structure.