Oxotitanium(IV) complexes of some bis‐unsymmetric Schiff bases: Synthesis,structural elucidation and biomedical applications

A number of oxotitanium(IV) complexes of the type TiOL with bis‐unsymmetric dibasic tetradentate Schiff base (LH₂) containing ONNO donor atoms have been synthesized. Mono‐Schiff base (OPD‐HNP) was prepared by the condensation of 1:3 molar ratio of 2‐hydroxy‐1‐naphthaldehyde (HNP) with o‐phenylenediamine (OPD). Dibasic unsymmetric tetradentate diamine Schiff bases were prepared by the reaction of OPD‐HNP with 2‐hydroxyacetophenone, 2‐hydroxypropeophenone, benzoylacetone, acetylacetone and ethylacetoacetate. Further, titanylacetylacetonate was reacted with these ligands to obtain their metal complexes. On the basis of analytical and physiochemical data, the formation of complexes as TiOL was suggested having square pyramidal geometry. Quantum mechanical approach also confirmed this geometry. The assessment of the synthesized ligands and their complexes showed that some behave as good inhibitors of mycelial growth against selected phytopathogic fungi but weak inhibitors against some selected bacteria. A few of them also showed antioxidant properties.     

Squalene-hopene cyclase: insight into the role of the methyl group on the squalene backbone upon the polycyclization cascade. Enzymatic cyclization products of squalene analogs lacking a 26-methyl group and possessing a methyl group at C7 or C11

To provide deep insight into the polycyclization reaction of squalene, some analogs were synthesized and incubated with the cell-free homogenates of the recombinant Escherichia coli encoding the wild-type squalene cyclase. The presence of C6-Me leads to an efficient polycyclization cascade. Substitution of the C14-H and the C18-H with a methyl group halted the polycylization reaction at the tricyclic ring stage having a 6/6/6-fused ring system and the tetracycle with a 6/6/6/6-fused ring, respectively, both of which were produced according to a Markovnikov closure. Replacement of the C7-H and the C11-H with a methyl group led to no cyclization. These results, in conjunction with our previous reports, indicated that the methyl positions are important for bringing to completion of the normal polycylization reaction and further demonstrated that the precise steric bulk size at the methyl positions of squalene is critical to the correct folding and the strong binding of the substrate to the squalene cyclase.     

Titanium (IV) complexes of some tetra‐dentate symmetrical bis‐Schiff bases of 1,6‐hexanediamine: Synthesis,characterization, and in silico prediction of potential inhibitor against coronavirus (SARS‐CoV‐2)

Symmetrical bis‐Schiff bases (LH ₂) have been synthesized by the condensation of 1,6‐hexanediamine (hn) and carbonyl or dicarbonyl. One of the synthesized Schiff bases has been subjected to the molecular docking for the prediction of their potentiality against coronavirus (SARS‐CoV‐2). Molecular docking revealed that tested Schiff base possessed high binding affinity with the receptor protein of SARS CoV‐2 compared with hydroxychloroquine (HCQ). The ADMET analysis showed that ligand is non‐carcinogenic and less toxic than standard HCQ. Schiff bases acting as dibasic tetra‐dentate ligands formed titanium (IV) complexes of the type [TiL(H₂O)₂Cl₂] or [TiL(H₂O)₂]Cl₂ being coordinated through ONNO donor atoms. Ligands and complexes were characterized by the elemental analysis and physicochemical and spectroscopic data including FTIR, ¹H NMR, mass spectra, UV‐Visible spectra, molar conductance, and magnetic measurement. Optimized structures obtained from quantum chemical calculations supported the formation of complexes. Antibacterial, antifungal, and anti‐oxidant activity assessments have been studied for synthesized ligands and complexes.     

Enzymatic cyclization reactions of geraniol, farnesol and geranylgeraniol, and those of truncated squalene analogs having C20 and C25 by recombinant squalene cyclase

The substrate specificity of squalene-hopene cyclase was investigated using the C10-C25 analogs including naturally occurring substances, e.g. geraniol (C10), farnesol (C15) and geranylgeraniol (C20). No cyclization occurred for geraniol, but a significantly high conversion ratio (64%) was observed for farnesol, yielding the cyclic sesquiterpenes consisting of 6/6-fused bicyclic ring systems. Among them, an attractive compound having C30 was produced, in the structure of which acyclic the farnesol unit is linked to the bicyclic skeleton through ether linkage. Conversion of geranylgeraniol was low (ca. 12%). The squalene analogs having C20 and C25 also were cyclized in yields of ca. 33-36%, but the analogs having the methyl group at C7 and/or at C11 underwent no cyclization; the large steric bulk size of C7-Me and/or C11-Me, which is arranged in [small alpha]-disposition for all the pre-chair conformation, would have interacted repulsively with the cyclase recognition site near to the C7 and/or C11, resulting in no construction of the all-chair conformation inside the reaction cavity. A relatively low yield of geranylgeraniol indicated that a less bulky hydrogen atom must be located at C14 for the efficient polycyclization reaction. The squalene cyclase shows remarkably broad substrate specificity to accept the truncated analogs having carbon-chain lengths of C(15)-C25 in addition to C30.     

Importance of the methyl group at C10 of squalene for hopene biosynthesis and novel carbocyclic skeletons with 6/5 + 5/5 + (6) ring system(s)

[reaction: see text] Incubation of (6E,10E,14E,18E)-2,6,10,19,23-pentamethyl-tetracosa-2,6,10,14,18,22-hexaene with Alicyclobacillus acidocaldarius hopene cyclase afforded four products having two types of carbocyclic skeletons, i.e., two hopane products and two products having an unprecedented carbocyclic skeleton of 6/5 + 5/5 +6 pentacyclic and 6/5 + 5/5 tetracyclic ring systems. The former two hopane skeletons were formed from the bioconversion of C15-desmethylsqualene and the latter two skeletons from that of C10-desmethylsqualene.