Lozan Todorov

The experimental IR and Raman vibrational spectra of a hydrated La(III) complex with a 1,2,3-triazole ligand were characterized by using four different Density Functional Theory (DFT) levels and two accurate scaling procedures. In the theoretical calculations, the hydration water in the experimental sample was considered under the Discrete Model (DM) with different numbers of explicit water molecules and different positions around the La(III) ion and the carboxylate groups. The predicted IR spectra at the M06-2X/Lanl2dz level appear to be the closest to the experimental ones. Based on the optimized structures, molecular properties and global chemical descriptors were also calculated, and the findings obtained are discussed in detail herein. Additionally, several photophysical properties were determined in both the free ligand and in several lanthanide complexes, and with the sample in the solid state and in DMSO solution. A blue shift in the fluorescence of the complexes was observed compared to the free ligand, as well as in the solid-state sample compared to the solution.

Unpredictable, dose-limiting toxicity remains a challenge in cancer treatment. We evaluated dihydropyrimidine dehydrogenase (DPD) and UDP-glucuronosyltransferase 1A1 (UGT1A1) plasma levels in the context of chemotherapy-induced toxicity and disease progression. Seventy gastrointestinal cancer patients (30 FOLFOX; 40 FOLFIRI) were enrolled. DPD and UGT1A1 plasma levels were determined using ELISA. Univariable and bivariable analyses and a general linear model (GLM) framework were used. Post-infusional reductions in white blood cell and granulocyte counts were observed. For FOLFOX, the granulocyte counts decreased by 17% (r = 0.54; p = 0.0030), while FOLFIRI caused a 41% reduction (r = 0.43; p = 0.0063). DPD levels were lower in FOLFOX than in FOLFIRI (2.543 vs. 3.579; p = 0.0363; Cohen’s d = 0.52). The multiple linear regression models associated DPD levels with cancer progression (b* = 0.258, p = 0.034). The bivariate analysis and multiple linear regression indicated some trends of association between UGT1A1 levels and reduction in white blood cell (b* = 0.359, p = 0.042) and granulocyte counts (b* = 0.383, p = 0.030) among FOLFIRI-treated patients. These preliminary observations suggest that DPD and UGT1A1 might contribute to evaluating response assessment.

A novel Ce(III) complex with the triazole ligand 2b, which presents four H-bonded sites with amino acids of the MMP-2 receptor, was synthesized. The experimental IR and Raman spectra of this Ce(III) complex were well-interpreted based on their comparison to the theoretical scaled spectra using the scaling equations determined by two procedures and four density functional theory (DFT) levels. Therefore, the structure predicted for the synthesized Ce(III) complex was clearly characterized and confirmed. The potential antioxidant action of this complex was compared with the analogous La(III) complex, and it was found that the coordination of ligand 2b with Ce(III) improves the ligand’s ability to participate in single-electron transfer (SET), as observed in the ABTS^·+ assay, and this complex seems to scavenge the stable radical much more actively compared to its La(III) counterpart. Additionally, interactions with potassium superoxide and sodium hypochlorite indicate a high pro-oxidant behavior of the complex. The effects of different ligands on the geometric parameters, atomic charges, and molecular properties of the Ce(III) complex were analyzed at four DFT levels, and several relationships were clearly established. These relationships can facilitate the selection of new ligands with improved properties in the design of novel lanthanide–triazole carboxylate complexes with promising biological activity. The ligand size increase in the complexes facilitates the electronic transfer of negative charge, and the low HOMO (highest occupied molecular orbital)–LUMO (lowest unoccupied molecular orbital) energy gap indicates a large reactivity and low energy for their excitation.

The effect of La, Ce, Pr and Nd ions on four Ln(ligand)₃ complexes and at three DFT levels of calculation was analyzed. Four ligands were chosen, three of which were based on the 1,2,3-triazole ring. The DFT methods used were B3LYP, CAM-B3LYP and M06-2X. The relationships established were between the geometric parameters, atomic charges, HOMO-LUMO energies and other molecular properties. These comparisons and trends will facilitate the synthesis of new complexes by selecting the ligand and lanthanide ion best suited to the desired property of the complex. The experimental IR and Raman spectra of Ln(2b′)₃ complexes where Ln = La, Ce, Pr, Nd, Sm, Gd, Dy, Ho and Er ions have been recorded and compared to know the effect of the lanthanide ion on the complex. The hydration in these complexes was also analyzed. Additionally, the effect of the type of coordination center on the ability of an Ln(ligand)₃ complex to participate in electron exchange and hydrogen transfer was investigated using two in vitro model systems—DPPH and ABTS.

Coumarin (2H-1-benzopyran-2-one) presents the fundamental structure of an enormous class of biologically active compounds of natural, semi-synthetic, and synthetic origin. Extensive efforts are continually being put into the research and development of coumarin derivatives with medicinal properties by the broad scientific community. Transition metal coordination compounds with potential biological activity are a “hot topic” in the modern search for novel drugs. Complexation with transition metals can enhance the physiological effect of a molecule, modify its safety profile, and even imbue it with novel attributes of interest in the fields of medicine and pharmacy. The present review aims to inform the reader of the latest developments in the search for coumarin transition metal complexes with biological activity, their potential applications, and structure-activity relationships, where such can be elucidated. Each section of the present review addresses a certain kind of biological activity (antiproliferative, antioxidant, antimicrobial, etc.), explores the most recent discoveries in the field, and, at the same time, tries to offer useful perspectives for potential future investigations.

Four models of Ce(III) complexes with four ligands based on a 1,2,3-triazole derivatives were studied at four DFT levels. The effect of different ligands on the atomic charge value on the cerium ion was analyzed. Several relationships were clearly established between this atomic charge and that of the surrounding atoms, as well as with several geometric parameters of the ligand and with the molecular properties of the Ce(III) complex. The experimental IR and Raman spectra of the newly obtained Ce(III) complex with the (pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylate ligand were interpreted based on their comparison to the theoretical scaled ones using the scaling equations determined by two procedures and four DFT levels. Therefore, the structure predicted for the synthesized Ce(III) complex was clearly characterized and confirmed. The potential antioxidant action of Ce(III) complex was elucidated and compared with other Ln(III) complexes in order to find out the differences in their biological activity profiles.

The 1,2,3-triazole derivative 2-(4-chlorophenyl)-5-(pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylic acid with potential anticancer activity was used as a ligand in complex formation with the lanthanum(III) ion. The molecular structure and vibrational spectra of the complex were optimized at three DFT levels, and the scaled IR and Raman spectra were compared to the experimental ones. Several scaling procedures were used. Through a detailed analysis, the structure predicted for the newly synthetized La(III) complex was confirmed by the good accordance of the calculated/experimental IR and Raman spectra. The best DFT method appeared to be M06-2X with the Lanl2mb basis set, followed closely by Lanl2dz. The effect of the lanthanide atom on the molecular structure and atomic charge distribution of the triazole ring was evaluated. The potential free radical scavenging activity of both the ligand and the complex was investigated in several radical-generating model systems. The potential mechanisms of antioxidant action (hydrogen atom transfer (HAT) and single-electron transfer (SET)) were elucidated.

The 1,2,3-triazole derivative 2-(4-chlorophenyl)-5-(pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylic acid with potential anticancer activity was used as a ligand in complex formation with the lan-thanum(III) ion. The molecular structure and vibrational spectra of the complex were optimized at three DFT levels and the scaled IR and Raman spectra were compared to the experimental ones. Several scaling procedures were used. Through a detailed analysis, the structure predicted for the newly synthetized La(III) complex was confirmed by the good accordance of the calculat-ed-experimental IR and Raman spectra. The best DFT method appears to be M06-2X with the Lanl2mb basis set, followed closely by Lanl2dz. The effect of the lanthanide atom on the molecular structure and atomic charge distribution of the triazole ring was evaluated. Potential free radical scavenging activity of both, ligand and complex, was investigated in several radical-generating model systems. Potential mechanisms of antioxidant action (hydrogen atom transfer – HAT and single electron transfer - SET) were elucidated.

The emergence of drug-resistant bacterial and fungal pathogens has highlighted the urgent need of innovative antimicrobial therapeutics. Transition metal complexes with biologically active ligands (coumarins, terpyridines, triazoles, uracils, etc.) have long been investigated for antimicrobial activity. 1,2,3-Triazoles and their molecular derivatives are well known for a plethora of physiological activities, including antibacterial and antifungal. The aim of the present mini-review is to inform the reader about research conducted on potential antimicrobial 1,2,3-triazole complexes with transition metals. What the authors find surprising is how little such research and experimentation has actually been performed and reported in scientific literature. The goal is to highlight research efforts up to now and impress upon the reader the vast perspectives for novel, effective medicinal substances hidden in this yet unexplored field.

Ubiquitously present in plant life, coumarins, as a class of phenolic compounds, have multiple applications—in everyday life, in organic synthesis, in medicine and many others. Coumarins are well known for their broad spectrum of physiological effects. The specific structure of the coumarin scaffold involves a conjugated system with excellent charge and electron transport properties. The antioxidant activity of natural coumarins has been a subject of intense study for at least two decades. Significant research into the antioxidant behavior of natural/semi-synthetic coumarins and their complexes has been carried out and published in scientific literature. The authors of this review have noted that, during the past five years, research efforts seem to have been focused on the synthesis and examination of synthetic coumarin derivatives with the aim to produce potential drugs with enhanced, modified or entirely novel effects. As many pathologies are associated with oxidative stress, coumarin-based compounds could be excellent candidates for novel medicinal molecules. The present review aims to inform the reader on some prominent results from investigations into the antioxidant properties of novel coumarin compounds over the past five years.