Increasing the Efficacy of Seproxetine as an Antidepressant Using Charge–Transfer Complexes

The charge transfer interactions between the seproxetine (SRX) donor and π-electron acceptors [picric acid (PA), dinitrobenzene (DNB), p-nitrobenzoic acid (p-NBA), 2,6-dichloroquinone-4-chloroimide (DCQ), 2,6-dibromoquinone-4-chloroimide (DBQ), and 7,7′,8,8′-tetracyanoquinodi methane (TCNQ)] were studied in a liquid medium, and the solid form was isolated and characterized. The spectrophotometric analysis confirmed that the charge–transfer interactions between the electrons of the donor and acceptors were 1:1 (SRX: π-acceptor). To study the comparative interactions between SRX and the other π-electron acceptors, molecular docking calculations were performed between SRX and the charge transfer (CT) complexes against three receptors (serotonin, dopamine, and TrkB kinase receptor). According to molecular docking, the CT complex [(SRX)(TCNQ)] binds with all three receptors more efficiently than SRX alone, and [(SRX)(TCNQ)]-dopamine (CTcD) has the highest binding energy value. The results of AutoDock Vina revealed that the molecular dynamics simulation of the 100 ns run revealed that both the SRX-dopamine and CTcD complexes had a stable conformation; however, the CTcD complex was more stable. The optimized structure of the CT complexes was obtained using density functional theory (B-3LYP/6-311G++) and was compared.     

Synthesis of Cyano-Benzylidene Xanthene Synthons Using a Diprotic Brønsted Acid Catalyst,and Their Application as Efficient Inhibitors of Aluminum Corrosion in Alkaline Solutions

Novel cyano-benzylidene xanthene derivatives were synthesized using one-pot and condensation reactions. A diprotic Brønsted acid (i.e., oxalic acid) was used as an effective catalyst for the promotion of the synthesis process of the new starting xanthene–aldehyde compound. Different xanthene concentrations (ca. 0.1–2.0 mM) were applied as corrosion inhibitors to control the alkaline uniform corrosion of aluminum. Measurements were conducted in 1.0 M NaOH solution using Tafel extrapolation and linear polarization resistance (LPR) methods. The investigated xanthenes acted as mixed-type inhibitors that primarily affect the anodic process. Their inhibition efficiency values were enhanced with inhibitor concentration, and varied according to their chemical structures. At a concentration of 2.0 mM, the best-performing studied xanthene derivative recorded maximum inhibition efficiency values of 98.9% (calculated via the Tafel extrapolation method) and 98.4% (estimated via the LPR method). Scanning electron microscopy (SEM) was used to examine the morphology of the corroded and inhibited aluminum surfaces, revealing strong inhibitory action of each studied compound. High-resolution X-ray photoelectron spectroscopy (XPS) profiles validated the inhibitor compounds’ adsorption on the Al surface. Density functional theory (DFT) and Monte Carlo simulations were applied to investigate the distinction of the anticorrosive behavior among the studied xanthenes toward the Al (111) surface. The non-planarity of xanthenes and the presence of the nitrile group were the key players in the adsorption process. A match between the experimental and theoretical findings was evidenced.     

Multispectral and Molecular Docking Studies Reveal Potential Effectiveness of Antidepressant Fluoxetine by Forming π-Acceptor Complexes

Poor mood, lack of pleasure, reduced focus, remorse, unpleasant thoughts, and sleep difficulties are all symptoms of depression. The only approved treatment for children and adolescents with major depressive disorder (MDD) is fluoxetine hydrochloride (FXN), a serotonin selective reuptake inhibitor antidepressant. MDD is the most common cause of disability worldwide. In the present research, picric acid (PA); dinitrobenzene; p-nitro benzoic acid; 2,6-dichloroquinone-4-chloroimide; 2,6-dibromoquinone-4-chloroimide; and 7,7′,8,8′-tetracyanoquinodimethane were used to make 1:1 FXN charge-transfer compounds in solid and liquid forms. The isolated complexes were then characterized by elemental analysis, conductivity, infrared, Raman, and ¹H-NMR spectra, thermogravimetric analysis, scanning electron microscopy, and X-ray powder diffraction. Additionally, a molecular docking investigation was conducted on the donor moiety using FXN alone and the resulting charge transfer complex [(FXN)(PA)] as an acceptor to examine the interactions against two protein receptors (serotonin or dopamine). Interestingly, the [(FXN)(PA)] complex binds to both serotonin and dopamine more effectively than the FXN drug alone. Furthermore, [(FXN)(PA)]–serotonin had a greater binding energy than [FXN]–serotonin. Theoretical data were also generated by density functional theory simulations, which aided the molecular geometry investigation and could be beneficial to researchers in the future.     

The Trypanosoma cruzi TcrNT2 Nucleoside Transporter Is a Conduit for the Uptake of 5-F-2′-Deoxyuridine and Tubercidin Analogues

Among the scarce validated drug targets against Chagas disease (CD), caused by Trypanosoma cruzi, the parasite’s nucleoside salvage system has recently attracted considerable attention. Although the trypanocidal activity of tubercidin (7-deazapurine) has long been known, the identification of a class of 7-substituted tubercidin analogs with potent in vitro and in vivo activity and much-enhanced selectivity has made nucleoside analogs among the most promising lead compounds against CD. Here, we investigate the recently identified TcrNT2 nucleoside transporter and its potential role in antimetabolite chemotherapy. TcrNT2, expressed in a Leishmania mexicana cell line lacking the NT1 nucleoside transporter locus, displayed very high selectivity and affinity for thymidine with a K_m of 0.26 ± 0.05 µM. The selectivity was explained by interactions of 2-oxo, 4-oxo, 5-Me, 3′-hydroxy and 5′-hydroxy with the transporter binding pocket, whereas a hydroxy group at the 2′ position was deleterious to binding. This made 5-halogenated 2′-deoxyuridine analogues good substrates but 5-F-2′-deoxyuridine displayed disappointing activity against T. cruzi trypomastigotes. By comparing the EC₅₀ values of tubercidin and its 7-substituted analogues against L. mexicana Cas9, Cas9^ΔNT1 and Cas9^ΔNT1+TcrNT2 it was shown that TcrNT2 can take up tubercidin and, at a minimum, a subset of the analogs.     

Synthesis of new antidiabetic agent by complexity between vanadyl (II) sulfate and vitamin B1: Structural,characterization, anti‐DNA damage,structural alterations and antioxidative damage studies

Complexity between thiamine (vitamin B₁) and VSO4.xH₂O salt with the suggest formula, [VO (vitB₁)₂] has been synthesized by the chemical reaction in neutralization media pH = 7.5 at 70 °C. The assignments of the elemental analysis, conductivity measurements, FT‐IR, UV–Vis, ESR spectroscopy, thermal analyses (TGA‐DTA) and magnetic moment data visualize the stoichiometry, formula and chelation of the vanadyl (II) complex. The spectroscopic analyses revealed that vitamin B₁ reacted with vanadyl (II) ions as a bidentate ligand via hydroxyl ethyl‐oxygen and sulfur of the thiazole group. New vanadyl (II) complex has the protective effect against pancreatic toxicity induced by STZ. The target of this investigation was to assess the enhancement effect of new vanadyl (II)complex in two doses on pancreatic toxicity, oxidative stress, DNA damage and hyperglycemia persuade by STZ. The rats were divided into 7 groups; control group, STZ (diabetic untreated group) (50 mg/kg), STZ plus thiamine (10 mg/Kg) (Low dose), STZ plus thiamine (50 mg/Kg) (High dose), STZ plus VSO4. xH₂O (15 mg/kg), STZ + vanadyl (II) complex (10 mg/Kg) (Low dose), STZ+ vanadyl (II) complex (50 mg/Kg) (High dose). Vanadyl (II) complex in high dose afforded a significant decline in MDA level parallel to significant elevation in antioxidant enzymes (SOD, CAT, MPO and XO) in pancreas homogenates. It may be due to the capturing activities of reactive oxygen species by the new complex, which reduces oxidative damage and enhance antioxidant capacities. The novel complex succeeded in the restoration of lipid parameters to its normal levels beside lowering TNF‐α and CRP levels. The new complex also reduces hyperglycemia induced by STZ greatly and improve histological and ultrastructure of pancreas and has a high potency in reducing DNA damage in pancreatic tissues.     

A study of the conformational stability and the vibrational spectra of 2,3-dichloro-1-propanol

The conformational stability and the three rotor internal rotations in 2,3-dichloro-1-propanol were investigated at DFT-B3LYP/6-311 + G**, MP2/6-311 + G** and MP4(SDQ) levels of theory. From the calculated potential energy surface, ten distinct minima were located all of which were predicted to have real frequencies at the B3LYP level of theory. The calculated lowest energy minima in the potential curves of the molecule were predicted to correspond to the Ggg and Gtg1 structures. The observed broad and very intense infrared band centered at about 3370 cm^?1 supports the existence of the strong intermolecular H-bonding in 2,3-dichloro-1-propanol. The equilibrium constants for the conformational interconversion in the molecule were estimated from the calculated Gibb's energies at the B3LYP/6-311 + G** level of calculation and found to correspond to an equilibrium mixture of about 49% Ggg, 27% Gtg1, 5% Ggt and 5% Tgg conformations at 298.15 K.     

Theoretical studies on the bifunctionality of chiral thiourea-based organocatalysts: competing routes to C-C bond formation

The mechanism of enantioselective Michael addition of acetylacetone to a nitroolefin catalyzed by a thiourea-based chiral bifunctional organocatalyst is investigated using density functional theory calculations. A systematic conformational analysis is presented for the catalyst, and it is shown that both substrates coordinate preferentially via bidentate hydrogen bonds. The deprotonation of the enol form of acetylacetone by the amine of the catalyst is found to occur easily, leading to an ion pair characterized by multiple H-bonds involving the thiourea unit as well. Two distinct reaction pathways are explored toward the formation of the Michael product that differ in the mode of electrophile activation. Both reaction channels are shown to be consistent with the notion of noncovalent organocatalysis in that the transition states leading to the Michael adduct are stabilized by extensive H-bonded networks. The comparison of the obtained energetics for the two pathways allows us to propose an alternative mechanistic rationale for asymmetric C-C bond forming reactions catalyzed by bifunctional thiourea derivatives. The origin of enantioselectivity in the investigated reaction is also discussed.