Two-Electron Aromatics with Classical and Non-Classical Homobridges

Bishomotriborirane anions with a B-H-B bridge, 7, have been synthesized by a) protonation and b) methylation of bishomodianions, 3, as well as by c) hydride addition to 1,2,4-triboracyclopentanes, 15. Compounds 7 were characterized by ¹H, ¹³C and ¹¹B NMR spectroscopy and X-ray diffraction analyses. The suggested mechanism for the formation of 7 is supported by MP4SDTQ/6-311++G**//MP2(fc)/6-31+G* computations on [C₂B₃H₈]^- model compounds. Classical 1,2-dibora-4-borata-cyclopentane intermediates 16 undergo an intramolecular hydrogen shift to the B-B unit in their envelope conformation to give intermediates 17, which easily isomerize to 7. Relative energies for the parent compounds, 16u, 17u, 7u and the transition structures, TS-16/17u and TS-7/17u are predicted to be 30.7, 14.5, 0.0, 32.6 and 23.5 kcal mol^-1, respectively. The terms classical and non-classical homobridges are suggested for methylene and hydrogen bridges in 7 and in related compounds on the grounds of common building principles. The strength of homoaromaticity in 7u was estimated to be at least 23.5 kcal mol^-1, neglecting the much higher strain in 7u compared to TS-7/17u without a 3c2e bond.Electronic Supplementary Material available.     

The effect of calcium on the thermotropic properties of bovine blood coagulation factors IX and X and their activation intermediates and products

The thermotropic properties of bovine blood coagulation Factors IX and X, as well as the activation intermediates and products of these proteins, have been investigated by differential scanning microcalorimetry in the presence and absence of Ca²⁺. Bovine Factor IX displays a single thermal-denaturation transition characterized by a temperature midpoint (T_M) of 54.5 ± 0.5 °C and a calorimetric enthalpy (ΔH_c) of 105 ± 15 kcal/mol, in the absence of Ca²⁺. In the presence of Ca²⁺ concentrations sufficient to saturate its sites on Factor IX, the T_m value is increased to 57.0 ± 0.5 °C and the ΔH_c is virtually unchanged. When the activation intermediate, Factor IXα, is similarly analyzed in the absence of Ca²⁺, a broad, diffuse thermogram was obtained which did not lend itself to calculation of thermodynamic parameters. In the presence of Ca²⁺, Factor IXα displayed thermograms characterized by a T_M of 51.0 ± 0.5 °C and a ΔH_c of 109 ± 10 kcal/mol. The activated product, Factor IXaα, in the absence of Ca²⁺ (the values in the presence of saturating Ca²⁺ are given in parentheses), undergoes thermal denaturation with a T_M of 54.5 ± 0.5 °C (57.0 ± 0.5 °C) and a ΔH_c of 158 ±10 kcal/mol (156 ± 10 kcal/mol). Similarly, the terminal-activation product, Factor IXaβ, displays a T_M of 51.5 ± 0.5 °C (54.0 ± 0.5 °C) and a ΔH_c of 85 ± 5 kcal/mol (126 ± 10 kcal/mol). Bovine blood coagulation Factor X has been analyzed in this same fashion, and shows very similar thermal properties to Factor IX. The thermal denaturation of Factor X is represented by a T_M of 54.0 ± 0.5 °C (55.0 ± 0.5 °C) and a ΔH_c of 102 ± 10 kcal/mol (118 ± 10 kcal/mol), whereas its activated form, Factor Xaβ, possesses a T_M of 55.0 ± 0.5 °C (55.0 ± 0.5 °C) and a ΔH_c of 92.0 ± 5 kcal/mol (136 ± 10 kcal/mol). These studies indicate that, for many of these proteins, Ca²⁺ induces a conformational alteration to a more thermally stable form, which also requires the absorption of greater amounts of heat for thermal denaturation.     

Evidence for ditopic coordination of phosphate diesters to [Mg(15-crown-5)]<Superscript>2+</Superscript>. Implications for magnesium biocoordination chemistry

The interaction of a series of phosphate diesters and triesters (1=diphenyl phosphate, 2=dimethyl phosphate, 3=bis(2-ethylhexyl) phosphate, 4=trimethyl phosphate, 5=methyldiphenyl phosphate, 6=triphenyl phosphate) with [Mg(15-crown-5)]²⁺ (15-crown-5=1,4,7,10,13-pentaoxocyclopentadecane) was studied as a simplified model for the interaction of aqueous Mg²⁺ ion with phosphate-containing biomolecules such as RNA. Using electrospray mass spectrometry, we confirm the formation of 1:1 adducts in the gas phase. Proton and ³¹P NMR titration data were used to construct binding isotherms, and a 1:1 binding equilibrium was fit to the isotherms at room temperature to estimate the binding affinities. The binding affinity data are consistent with ditopic coordination of neutral dialkyl phosphate ligands to the [Mg(15-crown-5)]²⁺ unit. This involves inner-sphere coordination to the Mg²⁺ via an oxygen atom, which is complemented by a weak hydrogen-bonding interaction with the crown ether ligand. Ditopic interaction is consistent with low-temperature NMR spectra showing four different configurations for 1 coordinated to [Mg(15-crown-5)]²⁺, which are interpreted in terms of hindered rotation around the Mg–O_phos bond. Thermochemical analysis of the binding affinity data suggests that the second-shell interaction contributes only about 1 kcal/mol to the binding free energy, so additional factors, such as steric constraints, must be operative to give a preferred phosphate orientation in this system. However, the experimental data do suggest that second-shell interactions contribute as much as 40% of the total binding energy, consistent with the pronounced ability of aqueous Mg²⁺ to form salt-bridges linking secondary and tertiary elements of RNA structure.Abbreviations OTf trifluoromethanesulfonate - ESI-MS electrospray mass spectrometry     

Synthesis,cyclooxygenase inhibition and anti-inflammatory evaluation of new 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives possessing methanesulphonyl pharmacophore

A new series of 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives 13a–p were synthesized via aldol condensation of 3/4-nitroacetophenones with appropriately substituted aldehydes followed by cyclization of the formed chalcones with 4-methanesulfonylphenylhydrazine hydrochloride. All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity and ulcerogenic liability. All compounds were more potent inhibitors for COX-2 than COX-1. While most compounds showed good anti-inflammatory activity, compounds 13d, 13f, 13k and 13o were the most potent derivatives (ED₅₀?=?66.5, 73.4, 79.8 and 70.5?μmol/kg, respectively) in comparison with celecoxib (ED₅₀?=?68.1?μmol/kg). Compounds 13d, 13f, 13k and 13o (ulcer index?=?3.89, 4.86, 4.96 and 3.92, respectively) were 4–6 folds less ulcerogenic than aspirin (ulcer index?=?22.75) and showed approximately ulceration effect similar to celecoxib (ulcer index?=?3.35). In addition, molecular docking studies were performed for compounds 13d, 13f, 13k and 13o inside COX-2 active site which showed acceptable binding interactions (affinity in kcal/mol ?2.1774, ?6.9498) in comparison with celecoxib (affinity in kcal/mol ?6.5330).     

EFFECT OF TEMPERATURE AND IONOPHORES ON THE PERMEABILITY OF SYNAPTOSOMES

Synaptosomes swell rapidly in isosmotic solutions of glycerol or urea, but the swelling in solutions of larger non-electrolytes, such as erythritol, glucose or sucrose is slower. The permeability of synaptosomes to non-electrolytes is temperature dependent, and the low activation energies for the permeation of urea (13 kcal/mol) and erythritol (9.5 kcal/mol) indicate that the penetration of non-electrolytes into the synaptosomes does not imply complete dehydration of the molecules. The relative permeability of synaptosomes to cations, as measured by the rate of swelling in isosmotic solutions of acetate salts is in the order: NH⁺₄ > Na⁺ > Li⁺ > K⁺ > Ca²⁺. The ionophores, X-537A and nigericin, or valinomycin + FCCP, which promote exchange of cations for H⁺, cause swelling of synaptosomes in solutions of potassium salts of acetate or propionate, but not in KCI, whereas H⁺ release is higher in KCI medium. This suggests that the organic unions cross the membrane after combining with H⁺ to form the respective weak acids. The relative permeability to anions is in the order: acetate ? propionate > Cl^? > SO^2-₄? maleate ? succinate. The energies of activation for the permeability of synaptosomes to potassium acetate in the presence of X-537A or gramicidin D are 13 kcal/mol and 7.5 kcal/mol, respectively, which reflects different mechanisms of action for the two ionophores in the membranes.     

Alterations in phospholipid-dependent (Na++K+)-ATPase activity due to lipid fluidity: Effects of cholesterol and Mg2+

The (Na⁺+K⁺)-activated, Mg²⁺-dependent ATPase from rabbit kidney outer medulla was prepared in a partially inactivated, soluble from depleted of endogenous phospholipids, using deoxycholate. This preparation was reactivated 10 to 50-fold by sonicated liposomes of phosphatidylserine, but not by non-sonicated phosphatidylserine liposomes or sonicated phosphatidylcholine liposomes. The reconstituted enzyme resembled native membrane preparations of (Na⁺+K⁺)-ATPase in its pH optimum being around 7.0 showing optimal activity at Mg²⁺: ATP mol ratios of approximately 1 and a K_m value for ATP of 0.4 mM.Arrhenius plots of this reactivated activity at a constant pH of 7.0 and an Mg²⁺: ATP mol ratio of 1:1 showed a discontinuity (sharp change of slope) at 17 °C, With activation energy (E_a) values of 13–15 kcal/mol above this temperature and 30–35 kcal below it. A further discontinuity was also found at 8.0 °C and the E_a below this was very high (> 100 kcal/mol).Incresed Mg²⁺ concentrations at Mg²⁺: ATP ratios in excess of 1:1 inhibited the (Na⁺+K⁺)-ATPase activity and also abolished the discontinuities in the Arrhenius plots.The addition of cholesterol to phosphatidylserine at a 1:1 mol ratio partially inhibited (Na⁺+K⁺)-ATPase reactivation. Arrhenius plots under these conditions showed a single discontinuity at 20°C and E_a values of 22 and 68kcal/mol above and below this temperature respectively. The ouabain-insensitive Mg²⁺-ATPase normally showed a linear Arrhenius plot with an E_a of 8 kcal/mol. The cholesterol-phosphatidylserine mixed liposomes stimulated the Mg²⁺-ATPase activity, which now also showed a discontinuity at 20 °C with, however, an increased value of 14 kcal/mol above this temperature and 6 kcal/mol below. Kinetic studies showed that cholesterol had no significant effect on the K_m for ATP.Since both of cholesterol and Mg²⁺ are know to alter the effects of temperature on the fluidity of phospholipids the above result are discussed in this context.     

Synthesis and biological activity of pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one derivatives: in silico approach

Xanthine oxidase (XO) is responsible for the pathological condition called gout. Inhibition of XO activity by various pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidine-4-one derivatives was assessed and compared with the standard inhibitor allopurinol. Out of 10 synthesized compounds, two compounds, viz. 3-amino-6-(2-hydroxyphenyl)-1H-pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one (3b) and 3-amino-6-(4-chloro-2-hydroxy-5-methylphenyl)-1H-pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one (3g) were found to have promising XO inhibitory activity of the same order as allopurinol. Both compounds and allopurinol inhibited competitively with comparable Ki (3b: 3.56?µg, 3g: 2.337?µg, allopurinol: 1.816?µg) and IC₅₀ (3b: 4.228?µg, 3g: 3.1?µg, allopurinol: 2.9?µg) values. The enzyme–ligand interaction was studied by molecular docking using Autodock in BioMed Cache V. 6.1 software. The results revealed a significant dock score for 3b (?84.976?kcal/mol) and 3g (?90.921?kcal/mol) compared with allopurinol (?55.01?kcal/mol). The physiochemical properties and toxicity of the compounds were determined in silico using online computational tools. Overall, in vitro and in silico study revealed 3-amino-6-(4-chloro-2-hydroxy-5-methylphenyl)-1H-pyrazolo[3,4-d]thiazolo[3,2–a]pyrimidin-4-one (3g) as a potential lead compound for the design and development of XO inhibitors.     

A Study and Optimization of Complexation of Cobalt Ions with Dihydroquercetin in Aqueous Solutions

This work continues a series of studies devoted to complex formation of ions of biogenic metals with the flavonoid dihydroquercetin (DHQ). The interaction of Со²⁺ ions with DHQ in aqueous solutions has been investigated. It has been found that, at different pH of a solution, complex compounds (CC) with different stoichiometry are formed; a variation of the pH value of a solution from 6.0 to 7.0 results in the formation of compounds (1)–(3) with the metal : flavonoid ligand ratio (Met : L) from 1 : 2 at рН 6.0 (1), through 2 : 3 at pH 6.4–6.7 (2), to 1 : 1 at рН 6.8–7.0 (3). By using the thermogravimetric method and the data of the elemental analysis, the most probable composition of the compounds with the determination of the amount of bound water has been proposed: [CoL₂(H₂O)₄] for (1), [Co₂L₃(ОН)(H₂O)₄] for (2), and [CoL(ОН)(H₂O)₂] for (3). Conditions for the optimization of product yield in the complexation reaction of Со²⁺ ions with DHQ in an aqueous solution have been determined for compound (2): the рН value of solution 6.7; the reaction time 15 min; the temperature of the reaction solution 90°С; the molar ratio of the initial reagents DHQ : Со²⁺ 1 : 1.5; the initial concentration of DHQ 0.020 mol/L and that of Со²⁺ 0.030 mol/L; and the use of CoSO₄ ? 7H₂O as a source of cobalt ions. The yield of the product is 81.8%.

     

Purification and properties of indole 2,3-dioxygenase from maize leaves

An indole 2,3-dioxygenase was purified ca 38-fold from maize leaves. The enzyme had an MW of about 98000, an optimum pH of 5.0 and the energy of activation was 9.1 kcal/mol. The K_max for indole was 1.4 × 10^?4 M. The enzyme was inhibited by diethyldithiocarbamate, salicylaldoxime and sodium dithionite. The inhibition by diethyldithiocarbamate was specifically reversed by Cu²⁺. The dialysed enzyme was stimulated by Cu²⁺. Four atoms of oxygen were utilized in the disappearance of 1 mole of indole. Inhibition of the enzyme by -SH compounds and -SH group inhibitors, and their partial removal by Cu²⁺ only, suggested the involvement of -SH groups in binding of Cu²⁺ at the catalytic site.     

Computational study on the mechanisms of action of the potential anticancer drug trans-isopropylaminedimethylaminedichloroplatinum (trans-IPADMADP) and its cis isomer with DNA purine bases

The monofunctional and bifunctional bindings of the potential anticancer drug trans-isopropylaminedimethylaminedichloroplatinum (trans-IPADMADP) and its cis isomer to purine base in DNA are explored by using density functional theory and IEF-PCM solvation models. The computed lowest free energy barrier in the aqueous solution is 14.0/11.6 kcal/mol (from trans-Pt-chloroaqua complex to trans-/cis-monoadduct) for guanine(G), and 11.7/13.3 kcal/mol (from trans-Pt-chloroaqua complex to trans-/cis-monoadduct) for adenine(A). Our calculations demonstrate that the trans reactant complexes (or isolated reactants) can generate trans- or cis-monoadducts via similar trigonal bipyramidal transition state structures, suggesting that the monoadducts can subsequently close to form the bifunctional intrastrand Pt-DNA adducts and simultaneously distort DNA in the similar way as cisplatin. Our calculations show that Pt(isopropylamine)(dimethylamine)G₂²⁺ head-to-head path has the lowest free energy of activation at 17.6 kcal/mol, closely followed by the Pt(isopropylamine)(dimethylamine)GA²⁺ head-to-head path at 19.6 kcal/mol when the monofunctional cis-Pt-G complex serves as the reactant; while the Pt(isopropylamine)(dimethylamine)G₂²⁺ head-to-tail adduct has the lowest barrier of 20.5 kcal/mol, closely followed by the Pt(isopropylamine)(dimethylamine)GA²⁺ head-to-tail adduct at 23.0 kcal/mol if the monofunctional trans-Pt-G complex is the reactant.The calculated relatively lower activation energy barrier than that of cisplatin theoretically confirm that trans-[PtCl₂(isopropylamine)(dimethylamine)] is a potential anticancer drug as described by experiment.     

Interactive intoxicating and ameliorating effects of tannic acid,aluminum (Al3+), copper (Cu2+), and selenate (SeO42−) in wheat roots: a descriptive and mathematical assessment

Tannic acids and tannins are produced by plants and are important components of soil and water organic matter. These polyphenolic compounds form complexes with proteins, metals and soil particulate matter and perform several physiological and ecological functions. The tannic acid (TA) used in our study was a mixture of gallic acid and galloyl glucoses ranging up to nonagalloyl glucose. TA inhibited root elongation in wheat seedlings (Triticum aestivum L. cv. Scout 66) at concentrations >4 mg l^?1; but TA alleviated the toxicity of Al³⁺, Cu²⁺ and SeO₄^2?; and Al³⁺ and SeO₄^2? alleviated the toxicity of TA. The interactions of Al³⁺ and TA (each toxic but each alleviating the toxicity of the other) were stoichiometric. Growth was affected as though 1 kg TA bound 2.76 mol Al so strongly that if (mol Al)/(kg TA) <2.76, then free Al ≈ 0, and if (mol Al)/(kg TA) >2.76, then free TA ≈ 0. This stoichiometry is consistent with one mole of galloyl groups binding approximately 0.5 mol Al. Using this binding scheme, growth was modeled successfully on the basis of free TA and free Al. TA enhanced the negativity of root surfaces and enhanced the binding of Al and Cu there without enhancing their toxicity. These and other interactions among TA, Al³⁺, Cu²⁺, SeO₄^2?, Ca²⁺, Na⁺ and H⁺ were quantified with a comprehensive non‐linear equation with statistically significant coefficients.     

Spin Labeled Nucleoside Analogues: 4′-Hydroxymorpholin-2′-Ylpurines and Pyrimidines

Abstract

Upon borane-pyridine reduction, a series of nucleoside dialdehyde dioximes 2 underwent cyclization to the corresponding 4′-hydroxymorpholin-2′-ylpurines or pyrimidines 3 from which the peracetyl derivatives 4 were prepared. At room temperature, compounds 3 and 4 exist as a mixture of invertomers in which the 4′S (equatorial 4′-OH or 4′-OAc) predominates. A 14 kcal/mol, nitrogen inversion barrier was estimated from variable temperature experiments. N.O.E. and ³J_CH measurements established the anti conformation of the base-“sugar” bond. Compounds 3 spontaneously oxidized to the corresponding aminoxyl free radicals, EPR spectra of which showed that they existed in a chair conformation.     

Thermodynamics of B-Z Transition of Poly[d(G-C)] in a Water-Ethanol Solution. The “Tie Calorimetry”

Abstract

Poly[d(G-C)] in a 55% ethanol solution undergoes a transition from the Z form to the B form when the temperature is increased from 20° to 50°C. The enthalpy of the transition, ΔH_BA =—1.4 kcal/mol, has been determined with a “tie” polyamine which stabilizes the Z conformation. This value has been shown to be practically independent of ionic strength within the range of 5 x 10⁴ M—2 x 10³ M NaCl.     

Properties of spinach chloroplast fructose-1,6-diphosphatase

Photosynthetic fructose-1,6-diphosphatase (FDPase) fractions I and II, earlier purified from spinach leaves, show a similar amino acid composition, with the exception of a higher glutamic acid content in the latter. In both fractions glutamic and aspartic acids are the main amino acids. pH activity profiles of fractions I and II are similar, with optima at 8·65–8·70, both showing a high specificity for fructose- 1,6-diphosphate. These two fractions are Mg²⁺-dependent for activity, with an Optimum Mg²⁺ concentration of 10 mM in standard conditions, which shifts to 5 mM when the MG²⁺/EDTA ratio is increased to 10; Mn²⁺ and Co²⁺ are slightly active. EDTA enhances FDPase activity slightly, with an optimum at 0·4–0·8 mM. Cysteine has no activating effect, and acts as an inhibitor above 10 mM. Both I and II have an optimum substrate concentration of 4 mM, and the substrate inhibits at concns above this value. Kinetic velocity curves are sigmoidal, with the concave zone located in the range of physiological substrate concns. (Hill coefficient 1·75 for both). This suggests a strong regulatory role of fructose-1,6-diphosphate. K_m values are 1·4 × 10⁻³ M (fraction I) and 1·1 × 10⁻³ M (fraction II). The highest activity rate occurs at 60°, in accordance with the high thermostability of both fractions; the activation energies are 14·3 kcal/mol (fraction I) and 13·0 kcal/mol (fraction II).     

A computational study of barium blockades in the KcsA potassium channel based on multi-ion potential of mean force calculations and free energy perturbation

Electrophysiological studies have established that the permeation of Ba²⁺ ions through the KcsA K⁺-channel is impeded by the presence of K⁺ ions in the external solution, while no effect is observed for external Na⁺ ions. This Ba²⁺ “lock-in” effect suggests that at least one of the external binding sites of the KcsA channel is thermodynamically selective for K⁺. We used molecular dynamics simulations to interpret these lock-in experiments in the context of the crystallographic structure of KcsA. Assuming that the Ba²⁺ is bound in site S₂ in the dominant blocked state, we examine the conditions that could impede its translocation and cause the observed “lock-in” effect. Although the binding of a K⁺ ion to site S₁ when site S₂ is occupied by Ba²⁺ is prohibitively high in energy (>10 kcal/mol), binding to site S₀ appears to be more plausible (ΔG > 4 kcal/mol). The 2D potential of mean force (PMF) for the simultaneous translocation of Ba²⁺ from site S₂ to site S₁ and of a K⁺ ion on the extracellular side shows a barrier that is consistent with the concept of external lock-in. The barrier opposing the movement of Ba²⁺ is very high when a cation is in site S₀, and considerably smaller when the site is unoccupied. Furthermore, free energy perturbation calculations show that site S₀ is selective for K⁺ by 1.8 kcal/mol when S₂ is occupied by Ba²⁺. However, the same site S₀ is nonselective when site S₂ is occupied by K⁺, which shows that the presence of Ba²⁺ affects the selectivity of the pore. A theoretical framework within classical rate theory is presented to incorporate the concentration dependence of the external ions on the lock-in effect.     

The standard Gibbs free energy change of hydrolysis of alpha-D-ribose 1-phosphate

The standard Gibbs free energy change of hydrolysis of α-d-ribose 1-phosphate has been measured at pH 7.0, ionic strength 0.1 m, and 25 °C by combining the corresponding values of the two following reactions: adenosine + H₂O ág adenine + ribose (ΔG^0′ = ?2.3 ± 0.1 kcal/mol), catalyzed by adenosine nucleosidase, and ribose 1-phosphate + adenine ág adenosine + P_i (ΔG^0′ = ?3.1 ± 0.1 kcal/mol), catalyzed by adenosine phosphorylase. The standard Gibbs free energy changes were calculated for both reactions from the equilibrium constant. A value of -5.4 ± 0.15 kcal/mol, comparable to that of other hemiacetal phosphoric esters, was obtained for the hydrolysis of ribose 1-phosphate.     

Effect of Composition and Impurities on the Phosphorescence of Green-Emitting Alkaline Earth Aluminate Phosphor

Recent improvements to SrAl₂O₄:Eu²⁺, Dy³⁺ phosphors have enabled the use of luminescent hosts with a stable crystal structure and high physical and chemical stability, thus overcoming the bottleneck in the applicability of ZnS:Cu phosphors. However, enhancement of afterglow lifetime and brightness in SrAl₂O₄:Eu²⁺, Dy³⁺ phosphors remains a challenging task. Here, we have improved the afterglow characteristics in terms of persistence time and brightness by a systematic investigation of the composition of Eu-doped alkaline earth aluminate SrAl₂O₄:Eu²⁺, Dy³⁺ crystals. We found that a Dy³⁺/Eu²⁺ ratio of ~2.4 and ~0.935 mol Eu²⁺ (per mol of SrAl₂O₄) gave the brightest and longest emissions (11% and 9% increase for each). Doping with Si⁴⁺ also resulted in a slight increase in brightness up to ~15%. Doping with alkali metal or alkaline earth metal significantly enhanced the phosphorescence intensity. In particular, doping with 0.005 mol Li⁺ (per mol of SrAl₂O₄) alone boosted the phosphorescence intensity to 239% of the initial value, as compared to that observed for the non-doped crystal, while doping with 0.01 mol Mg²⁺ and 0.005 mol Li⁺ (per 1 mol SrAl₂O₄) boosted the phosphorescence intensity up to 313% of the initial value. The results of this investigation are expected to act as a guideline for the synthesis of bright and long persistent phosphors, and facilitate the development of persistent phosphors with afterglow characteristics superior to those of conventional phosphors.     

Synthesis and in vitro antitumor and antimicrobial activity of some 2,3-diaryl-7-methyl-4,5,6,7-tetrahydroindazole and 3,3a,4,5,6,7-hexahydroindazole derivatives

The synthesis of a series of 2,3-diaryl-7-methyl-4,5,6,7-tetrahydroindazole and 3,3a,4,5,6,7-hexahydroindazole derivatives substituted with various biologically-active function groups with anticipated chemotherapeutic activity is described. 4-(7-methyl-3-aryl-3,3a,4,5,6,7-hexahydro-indazol-2-yl)benzenesulfonamides 2a–c, which were employed as key intermediates in this study, were synthesized by cyclocondensation of 6-arylidene-2-methylcyclohexanones 1a–c with 4-hydrazinobenzenesulfonamide hydrochloride. A detailed discussion of the reactions utilized in the preparation of the intermediate and target compounds is reported, and the structures of the newly synthesized compounds were substantiated with IR, ¹H and ¹³C NMR spectral data and elementary microanalyses. Twenty of the newly synthesized compounds were selected by National Cancer Institute (NCI), Maryland, USA, to be evaluated for their antitumor activity and the results revealed that six compounds 3c, 4d,e, 5a,d and 8c exhibited broad spectrum of antitumor activity against most of the tested tumor cell lines. In addition, the in vitro antibacterial and antifungal activities of a number of the target compounds were also tested using the Agar-diffusion method. Some of these compounds have shown significant antibacterial and mild to moderate antifungal activities.     

In-silico analysis of Sirt2 from Schistosoma mansoni: structures,conformations, and interactions with inhibitors

Sirtuins are NAD+-dependent lysine deacetylases member of the class III HDAC family. These are demonstrated to be therapeutic targets in parasitic diseases like schistosomiasis. Observations suggested that sirtuin enzyme is necessary for the functionality of fe/male reproductive system, due to which SmSirt2 is treated as a potential therapeutic target. There are no structural and molecular features of SmSirt2 have been reported yet. In this study, homology modeling has been used to determine the three-dimensional features of the SmSITRT2. Further, structure validation has been performed by energy minimization and Ramachandran plot. Validated structures are further subjected to molecular docking and virtual screening to find the best lead molecules for downstream analysis. Ten lead molecules were selected while comparing virtual screening of hSirt2 and SmSirt2 both. These leads are further compared with AKG2 which is known inhibitor of hSirt2 (?8.8 kcal/mol). Out of selected 10 leads, four of them (ZINC23995485 (?9.5 kcal/mol), ZINC53298162 (?9.4 kcal/mol), ZINC70927268 (?10.0 kcal/mol), ZINC89878705 (?11.2 kcal/mol)) have shown better interaction with SmSirt2, in which ZINC89878705 (?11.2 kcal/mol) shows a more compact packing as compared to AKG2 and rest of ligands. These molecules could be further subject to in vitro study and model of SmSirt2 has been proposed for further structure-based drug design projects concerning sirtuins from Schistosoma mansoni.     

Bis-dibenzo[a.i]fluorenylidene, does it exist as stable 1,2-diradical?

The geometries, energies, and electronic properties of the two possible configurations of bis-[dibenzo[a.i]fluorenylidene] were investigated theoretically by density functional theory DFT B3LYP at the UB3LYP/6-311?+?G(2d,p) // UB3LYP/6-31?+?G(d,p) level of theory. According to the performed calculations, it was found that the singlet is 3.4?kcal?mol^-1 lower in energy compared to triplet state at room temperature. This gap is compared with those of other alkenes like ethylene, (61.9?kcal?mol^-1) tetra-tert-butyethylene, (6.4?kcal?mol^-1) and bis-fluorenylidene (19.5?kcal?mol^-1). These results confirm the experimental findings of the paramagnetic properties determined by Franzen and Joschek. The low singlet-triplet gap in the case of bis-[dibenzo[a.i]fluorenylidene] is the result of a steric destabilization of the singlet due to strain and stabilization of the triplet electronic state by delocalization of each free electron within each aromatic moiety. This correlates with the special electronic structure of the triplet state of this compound, where facial interaction of two hydrogen atoms lying close to the lobes of each p-orbital occupied with a single electron at the distorted double bond in the triplet electronic state.