Indeno[1,2-b]pyridin-5-one derivatives containing azo groups and their hydrazonal precursors: Synthesis,antimicrobial profile,DNA gyrase binding affinity,and molecular docking

The prevalence of germs that are resistant to many antibiotics is rising rapidly the world over. There is a large group of researchers actively looking for better medicines. Here, we designed two series of hydrazonal and indeno[1,2-b]pyridin-5-one bearing hydrazone and azo-groups to test their antimicrobial activity. Molecular structures of all derivatives were assured based on their spectral data and elemental analyses. Results of the antimicrobial activity of the tested hydrazone and azo compounds showed promising potential for several derivatives. The minimum inhibitory concentrations (MICs) of hydrazones 4a - h and 6a - g displayed good antibacterial reactivities with a range of 3.91–250 μg/mL and moderate antifungal activity with a range of 15.6–500 μg/mL. The most promising hydrazone 4f and azo- 6a compounds demonstrated MIC values against Streptococcus faecalis and Escherichia coli equal to 3.91 and 7.81 μg/mL, respectively. Moreover, azo compound 6a showed MIC value equal to 3.91 μg/mL against Enterobacter cloacae species. Additionally, derivative 4f exhibited a significant inhibitory profile against the E. coli gyrase A enzyme (IC₅₀ = 5.53 μg/mL). On the other hand, compound 6a (IC₅₀ 14.05 μg/mL) exhibited the lowest DNA gyrase inhibitory activity as compared to compounds 4f and reference standard drug novobiocin, IC₅₀ 5.53 and 1.88 μg/mL, respectively. Pharmacokinetic and pharmacodynamic profiles and molecular docking studies for the two most promising molecules 4f and 6a were computed and revealed that both compounds have good ADME profiles and high binding affinity to DNA gyrase binding site.     

Photobleaching Kinetics and Effect of Solvent in the Photophysical Properties of Indocyanine Green for Photodynamic Therapy

Indocyanine green is an attractive molecule for photodynamic therapy due to its near infrared absorption, resulting in a higher tissue penetration. However, its quantum yields of the triplet and singlet state have been reported to be low and then, reactive oxygen species are unlikely to be formed. Aiming to understand the ICG role in photodynamic response, its photobleaching behavior in solution has been studied under distinct conditions of CW laser irradiation at 780 and 808 nm, oxygen saturations and solvents. Sensitizer bleaching and photoproduct formation were measured by absorption spectroscopy and analyzed using the PDT bleaching macroscopic model to extract physical parameters. ICG photobleaching occurs even at lower oxygen concentrations, indicating that the molecule presents more than one way of degradation. Photoproducts were produced even in solution of less than 4 % oxygen saturation for both solvents and excitation wavelengths. Also, the amplitude of absorption related to J-dimers was increased during irradiation, but only in 50 % PBS solution. The formation of photoproducts was enhanced in the presence of J-type dimers under low oxygen concentration, and the quantum yields of triplet and singlet states were one order of magnitude and two times higher, respectively, when compared to ICG in distilled H₂O.     

A simple one-pot synthesis of 3-alkoxy-3-cyanocarboxylic acids: a rapid entry to new GABA derivatives

A simple one-pot procedure to obtain a series of new 3-alkoxy-3-cyanocarboxylic acids from the reaction of 4-alkoxy-1,1,1-trichloro-but-3-en-2-ones with sodium cyanide is described.     

Fe(II) hydrolysis in aqueous solution: A DFT study

Species arising from Fe(II) hydrolysis in aqueous solution have been investigated using density-functional methods (DFT). The different tautomers and multiplicities of each species have been calculated. The solvation energy has been estimated using the UAHF–PCM method. The hydrolysis free energies have been estimated and compared with the available experimental data. The different hydrolysis species have distinct geometries and electronic structures. The estimated ionization potential of the hydrolyzed species is linearly dependent to the number of hydroxyls present in the complex. The estimated Fe(II)/Fe(III) oxidation potential is in good agreement with previously published results about 0.29 V larger than the experimental value. The results highlight the importance of the chemical speciation in describing electron transfer processes at a molecular level. The PBE/TZVP/UAHF–PCM method has been found to describe correctly the hydrolysis free energies of Fe(II) with an average error about 5 kcal mol⁻¹ from the experimental values.     

Simultaneous determination of aluminoxamine and ferrioxamine in post-hemodialysis fluids by spectrophotometry and multivariate calibration

A spectrophotometric method for simultaneous determination of Al(III) and Fe(III) using the chelator Desferal® (desferrioxamine B) was developed. Partial least squares (PLS) regression was performed to resolve the overlapped signals obtained from Al(III) and Fe(III) complexes. The parameters controlling behavior of the system were investigated and optimum conditions were selected. PLS was the choice for the analysis of binary mixtures of Fe(III) and Al(III) over the range of 0.1 to 0.8 mg L^?1 by using the data of first derivative spectra. Absorbance data were taken between 200 and 600 nm. The calculated sensitivity values for the multivariate method were 4.88 and 5.64 for Al(III) and Fe(III), respectively. Multivariate detection limits were 0.075 and 0.064 mg L^?1 for Al(III) and Fe(III), respectively. The method was applied to real post-hemodialysis samples, and sample digestion by UV irradiation was discussed.     

Multiobjective vehicle routing problem with fixed delivery and optional collections

We present an adaption on the formulation for the vehicle routing problem with fixed delivery and optional collections, in which the simultaneous minimization of route costs and of collection demands not fulfilled is considered. We also propose a multiobjective version of the iterated local search (MOILS). The performance of the MOILS is compared with the $\epsilon $ -constrained ( $P_{\epsilon }$ ) ILS, the NSGA-II and the indicator-based multi-objective local search methods in the solution of 14 problem instances containing between 50 and 199 customers plus the depot. The results indicate that the MOILS outperformed the other approaches, obtaining significantly better average values for coverage, hypervolume and cardinality.