Tinidazole

Short peptaibol peptides, such as the 11-residue trichogin, can permeabilize membranes and induce ion transport, providing insights into the evolution of ion channels as well as potential strategies for antimicrobial drug design. In this study, extensive molecular dynamics simulations at the microsecond timescale are applied to investigate the aggregation of trichogin in POPC membranes and the induced ion transport under an applied transmembrane voltage. The trichogin peptide is found to convert from a membrane surface-bound state to an inserted state, followed by self-assembly into a variety of N-mer clusters in the membrane, with populations of 17%, 22%, 20%, and 11% for 2-mer to 5-mer clusters, respectively, at a protein-to-lipid ratio of 1:10 under a 200-mV applied voltage. A diverse range of self-assembled structures is identified, from barrel-stave oligomers (dimer to hexamer) to more complex stacked oligomers built from head-to-tail dimers. The trimer is found to be the most populated oligomer and serves as a seed for higher-order assemblies. The ion transport mechanism is identified through direct ion-crossing events under applied voltage, where K⁺ and Cl^- ions traverse the membrane via transient, channel-like pentameric and hexameric barrel-stave bundles. An additional transport pathway is identified in which the translocation of lipid headgroups into the bilayer center stabilizes a transient pore along the lumen of a pentamer, resembling a toroidal pore. Stacked oligomers formed from head-to-tail dimers are shown to be unfavorable for ion transport due to misaligned hydrophilic faces, preventing the formation of a continuous water-filled lumen. The peptide assemblies are found to be highly dynamic, with rapid association and dissociation of peptide from a cluster and frequent interconversion between the surface-bound and membrane-inserted state. These dynamic properties make the short peptide assemblies flexible and functional, though less stable and less ion selective compared with complex ion channels formed of longer peptides.

Cocrystal structures formed by trithiocyanuric acid (TTCA) and selected nitroimidazole derivatives, dimetridazole (DMZ·TTCA, C 5 H 7 N 3 O 2 ·C 3 H 3 N 3 S 3 ), tinidazole (TNZ·TTCA·MeOH, C 8 H 13 N 3 O 4 S·C 3 H 3 N 3 S 3 ·CH 3 OH), ornidazole (ONZ·TTCA·MeOH, C 7 H 10 ClN 3 O 3 ·C 3 H 3 N 3 S 3 ·CH 3 OH, and ONZ·TTCA·H 2 O, C 7 H 10 ClN 3 O 3 ·C 3 H 3 N 3 S 3 ·H 2 O) and ronidazole (RNZ·TTCA and 2RNZ·2TTCA, both C 6 H 8 N 4 O 4 ·C 3 H 3 N 3 S 3 ) were investigated to identify recurring drug–coformer aggregation patterns and factors determining supramolecular architecture. Structural analysis showed that TTCA adopts two principal supramolecular motifs: the hydrogen-bonded R22 (8) dimer and linear chain assemblies. Two dominant drug–coformer binding schemes were identified. The first involves N—H...N hydrogen bonding in the para position relative to the TTCA dimer, leading to four-molecule assemblies, which are accompanied by heteronuclear hydrogen bonding in the ortho position. The second motif is associated with TTCA linear chains, where drug molecules are linked through N—H...N interactions and further stabilized by direct intermolecular or solvent-mediated hydrogen bonding. The polymorphic structure 2RNZ·2TTCA combines both supramolecular strategies within a single-crystal architecture. Hirshfeld surface analysis and intermolecular energy calculations confirmed the importance of hydrogen-bond competition in determining the crystal packing and supramolecular organization in TTCA-based cocrystals.