[en] With the aim of obtaining compounds with promising properties, our team has been interested in the synthesis of aromatic Schiff bases containing triazole groups, thus combining the properties of Schiff bases with those of triazoles. A large number of bases have been obtained and studied, varying the type of triazole and/or the substituents (hydroxyl or halogen). In this contribution we present the effect of the position of the hydroxyl substituents and the type of triazole on the structure of the compound, and their antifungal properties. Four mono- and disubstituted Schiff bases will be presented, along with their structures and antifungal properties. To complete the work, a molecular docking study was carried out on the sterol 14-alpha demethylase protein (pdb: 6CR2) because of its structure, based on the design of new antifungal drugs

[en] Different strategies for the synthesis of symmetrical and unsymmetrical macrocyclic Schiff bases in the absence of metal ions are considered. General methods for performing macrocyclisation under thermodynamic or kinetic control are analysed. The key factors influencing the structure of macrocyclic azomethines are discussed.

[en] The alkylation of the ambient enolates of a methyl glycinate Schiff base with ethyl chloride was studied at B3LYP and MP2 levels with 6-31+G^* basis set. The free (E)-enolates and (Z)-enolate are similar in energy and geometry. The transition states for the alkylation of the free (E)/(Z)-enolate with ethyl chloride have similar energy barriers of ∼13 kcal/mol. However, with a lithium ion, the (E)-enolate behaves as an ambient enolate and makes a cyclic lithium-complex in bidentate pattern which is more stable by 11-23 kcal/mol than the (Z)-enolate-lithium complexes. And the TS for the alkylation of (E)-enolate-lithium complex coordinated with one methyl ether is lower in energy than those from (Z)-enolate-lithium complexes by 4.3-7.3 kcal/mol. Further solvation model (SCRF-CPCM) and reaction coordinate (IRC) were studied. This theoretical study suggests that the alkylation of ambient enolates proceeds with stable cyclic bidentate complexes in the presence of metal ion and solvent

[en] The transfer of a proton from the retinal Schiff base to the nearby Asp85 protein group is an essential step in the directional proton-pumping by bacteriorhodopsin. To avoid the wasteful back reprotonation of the Schiff base from Asp85, the protein must ensure that, following Schiff base deprotonation, the energy barrier for back proton-transfer from Asp85 to the Schiff base is larger than that for proton-transfer from the Schiff base to Asp85. Here, three structural elements that may contribute to suppressing the back proton-transfer from Asp85 to the Schiff base are investigated: (1) retinal twisting; (2) hydrogen-bonding distances in the active site; and (3) the number and location of internal water molecules. The impact of the pattern of bond twisting on the retinal deprotonation energy is dissected by performing an extensive set of quantum-mechanical calculations. Structural rearrangements in the active site, such as changes of the Thr89:Asp85 distance and relocation of water molecules hydrogen-bonding to the Asp85 acceptor group, may participate in the mechanism which ensures that following the transfer of the Schiff base proton to Asp85 the protein proceeds with the subsequent photocycle steps, and not with back proton transfer from Asp85 to the Schiff base

[en] Highlights: • The X-ray crystal structure of GAD from Lb. brevis CGMCC 1306 was determined at a resolution of 2.2 Å. • The coenzyme PLP forms an internal aldimine bond with residue K279. • The mutant T215A displayed the highest activity among all variants tested. • The flexible loop (Y308−E312) covering the active site is involved in the catalytic reaction. Glutamate decarboxylase (GAD), which is a unique pyridoxal 5-phosphate (PLP)-dependent enzyme, can catalyze α-decarboxylation of l-glutamate (L-Glu) to γ-aminobutyrate (GABA). The crystal structure of GAD in complex with PLP from Lactobacillus brevis CGMCC 1306 was successfully solved by molecular-replacement, and refined at 2.2 Å resolution to an R_work factor of 18.76% (R_free = 23.08%). The coenzyme pyridoxal 5-phosphate (PLP) forms a Schiff base with the active-site residue Lys279 by continuous electron density map, which is critical for catalysis by PLP-dependent decarboxylase. Gel filtration showed that the active (pH 4.8) and inactive (pH 7.0) forms of GAD are all dimer. The residues (Ser126, Ser127, Cys168, Ile211, Ser276, His278 and Ser321) play important roles in anchoring PLP cofactor inside the active site and supporting its catalytic reactivity. The mutant T215A around the putative substrate pocket displayed an 1.6-fold improvement in catalytic efficiency (k_cat/K_m) compared to the wild-type enzyme (1.227 mM⁻¹ S⁻¹ versus 0.777 mM⁻¹ S⁻¹), which was the highest activity among all variants tested. The flexible loop (Tyr308–Glu312), which is positioned near the substrate-binding site, is involved in the catalytic reaction, and the conserved residue Tyr308 plays a vital role in decarboxylation of L-Glu.

[en] The transfer of a proton from the retinal Schiff base to the nearby Asp85 protein group is an essential step in the directional proton-pumping by bacteriorhodopsin. To avoid the wasteful back reprotonation of the Schiff base from Asp85, the protein must ensure that, following Schiff base deprotonation, the energy barrier for back proton-transfer from Asp85 to the Schiff base is larger than that for proton-transfer from the Schiff base to Asp85. Here, three structural elements that may contribute to suppressing the back proton-transfer from Asp85 to the Schiff base are investigated: (1) retinal twisting; (2) hydrogen-bonding distances in the active site; and (3) the number and location of internal water molecules. The impact of the pattern of bond twisting on the retinal deprotonation energy is dissected by performing an extensive set of quantum-mechanical calculations. Structural rearrangements in the active site, such as changes of the Thr89:Asp85 distance and relocation of water molecules hydrogen-bonding to the Asp85 acceptor group, may participate in the mechanism which ensures that following the transfer of the Schiff base proton to Asp85 the protein proceeds with the subsequent photocycle steps, and not with back proton transfer from Asp85 to the Schiff base

[en] Three Schiff base complexes of Cd²⁺ have been investigated polarographically in 60% menthanol-water medium at 26⁰C. The Schiff bases used are salicyladehyde tris buffer (ST), benzaldehydetris buffer (BT) and vanillin tris buffer (VT). Cd-ST and Cd-VT complexes produce reversible reduction wave at dme, while Cd-BT gives a quasi reversible wave. Stability constants of the complexes have been determined and the standard overall electrode reaction rate constant (ksub(e)sup(o)) B of the Cd-BT complex is determined by three different methods. The log β values of complexes are : Cd-ST, 2.72; Cd-VT, 4.90; and Cd-BT, 4.41. (author)

[en] The new dioxouranium (VI) Schiff base complexes [UO₂(sal-OAP)(H₂O)], [UO₂(sal-OAP)(py)], [UO₂(sal-OAP)(DMF)] and [UO₂(sal-OAP)(Et₃N)](sal-OAP orthoaminophenolsalicylideneiminato) have been prepared, and their i.r. spectra recorded and assigned on the basis of C_s symmetry. The bond stretching force constants of the uranyl bonds, F_U=O, were calculated as 661.7 Nm^-1, 676.1 Nm^-1, 674.5 Nm^-1 and 674.5 Nm^-1 for [UO₂(sal-OAP)(H₂O)], [UO₂(sal-OAP)(DMF)], [UO₂(sal-OAP)(py)] and [UO₂(sal-OAP)(Et₃N)], respectively. The corresponding values of the U = O bond lengths were calculated to be 1.745 A, 1.741 A, 1.742 A and 1.742 A. (author)

[en] Computer simulation is used for comparative investigation of the molecular dynamics of rhodopsin containing the chromophore group (11-cis-retinal) and free opsin. Molecular dynamics is traced within a time interval of 3000 ps; 3 × 10⁶ discrete conformational states of rhodopsin and opsin are obtained and analyzed. It is demonstrated that the presence of the chromophore group in the chromophore center of opsin influences considerably the nearest protein environment of 11-cis-retinal both in the region of the β-ionone ring and in the region of the protonated Schiff base bond. Based on simulation results, a possible intramolecular mechanism of keeping rhodopsin as a G-protein-coupled receptor in the inactive state, i.e., the chromophore function as an efficient ligand antagonist, is discussed.

[en] This thesis presents the synthesis and characterization of novel rhenium and technetium complexes using as complexing agents asymmetric ligands (Schiff's bases type ligands) and triamines ligands derived from diethylenetriamine. The asymmetric ligands were synthesized by condensation reactions between 2,2'- dihydroxybenzophenone and the aliphatic amines ethylenediamine and diethylenetriamine, giving rise, respectively, to the ligands 2,2'-(((2-aminoetill)imino) methylene)diphenol (HL1) and 2,2'-(((2-((2-aminoethyl)amino)ethyl)imino) methylene) diphenol (HL2). The symmetrical ligands were synthesized by condensation reactions between benzaldehyde, 4-hydroxybenzophenone and 3- and 4-methoxybenzaldehyde with the aliphatic amine diethylenetriamine, resulting in the formation, respectively, of the symmetrical tridentated ligands trihydrochloride N1-benzyl-N2-(2- (benzylamino)ethyl)ethane-1,2-diamine (HL3), 4,4'-(((azanodiilbis(ethane-2,1- diyl))bis(azanediil))bis(phenilmetileno))diphenol (HL4), trihydrochloride N1-(4- methoxybenzyl)-N2-(2-((4-methoxybenzyl)amino)ethyl)ethane-1,2-diamine (HL5) and trihydrochloride N1-(3-methoxybenzyl)-N2-(2-((3-methoxybenzyl)amino)ethyl)ethane- 1,2-diamine (HL6). Complexation reactions were carried out using ReI and TcI as metal precursors. The complex [Re(CO)5Br] was used as ReI precursor. Neutral complexe of the type fac-[Re(CO)3(L1)] and cationic complexes of the type fac- [Re(CO)₃(HL2,3,4,5,6)]Br were obtained. The ligands and complexes were characterized by melting point, elemental analysis (CHN), infrared absorption spectroscopy, UV-visible absorption spectroscopy, ¹H and ¹³C nuclear magnetic resonance spectroscopy, mass spectrometry (MS-ESI) and for the complexes with the ligands HL1,2,5,6, single crystal X ray diffraction method. Labeling studies were carried out for the HL3 ligand with the complex fac- [[^99mTc](H₂O)(CO)₃]+, forming the complex fac-[[^99mTc](CO)3(HL3)]Br and other species in solution, which were separated by high performance liquid chromatography (HPLC). Additionally, a comparative study was done between the conventional (heating) and the synthesis method using microwaves. The technetium complex was characterized by HPLC and electrophoresis on paper. Stability tests were conducted on cysteine, histidine and PBS buffer. The stability tests showed that the compound presents good stability over a 3 hour period. The lipophilic character of the complex was confirmed by the determination of the partition coefficient. In addition, In vitro biological tests of captation and influx were performed on B16F10 cells (murine melanoma). The cells captured around 4.2% of the complex fac-[[^99mTc](CO)3(HL3)]Br and retained 20% of the amount inside after 60 minutes of incubation. The Trypan blue exclusion test of cell viability showed stability of the cells during the influx and captation experiments, front of the radioactive species, showing cell viability greater than 90% in all cases. (author)