Kinetic and thermodynamic analysis of 10-hydroxy-camptothecin hydrolysis at physiological pH

To derive accurately the thermodynamic parameters governing the hydrolysis of the lactone ring at physiological pH, a derivative spectrophotometric technique was used for the simultaneous estimation of lactone and carboxylate forms of the 10-hydroxy-camptothecin (10-HC). Validation of the analytical method was done with respect to reproducibility, percent recovery, and level of detection. Hydrolysis of the lactone ring of 10-HC followed a 1st order decay with a rate constant equal to (0.0281 ± 0.001) min⁻¹ in PBS at pH 7.4 and at a temperature of 310 K. The activation energy for the hydrolysis reaction as calculated from the Arrhenius equation was (79.41 ± 0.92) kJ · mol⁻¹, whereas the enthalpy and entropy of hydrolysis of 10-hydroxy-camptothecin were on average 12.45 kJ · mol⁻¹ and 52.37 J · K⁻¹ · mol⁻¹, respectively. The positive enthalpy and entropy values of the 10-HC-lactone hydrolysis indicate that the reaction is endothermic and entropically driven.     

Mechanisms of amine-catalyzed organosilicate hydrolysis at circum-neutral pH

Mono- and polyamines can catalyze the hydrolysis and condensation of organosilicate starting materials in biomimetic silica synthesis pathways at circum-neutral pHs and room temperature. Our study is focused on understanding the mechanistic role of amines in catalyzing the hydrolysis process that precedes condensation. We have conducted (29)Si NMR experimental studies over a range of temperature and pHs for the hydrolysis rates of trimethylethoxysilane (TMES), a model compound with only one hydrolyzable bond, combined with quantum mechanical hybrid density functional theory calculations of putative intermediate and transition-state structures for TMES and tetramethyl orthosilicate (TMOS). Comparison of calculated energies with experimentally determined activation energies indicates that amine catalysis of TMES is primarily a consequence of the amine's acidity at neutral pH. The proton released by the amine is transferred to the organosilicate, producing a protonated ethoxy leaving group that can be displaced by water in an S(N)2 reaction. For TMOS, the activation energy of proton-transfer coupled with S(N)2 substitution is comparable to that for Corriu's nucleophile-activated nucleophilic displacement, such that the mechanism of amine-catalyzed hydrolysis is dependent mostly on the ambient pH conditions as well as the type of amine. The relevance of our results to biological silica precipitation is discussed.     

Synthetic method for multifunctionalized oligoarenes using pinacol esters of hydroxyphenylboronic acids

A synthetic method for multifunctionalized oligoarenes using rapid Suzuki-Miyaura coupling of pinacol esters of hydroxyphenylboronic acids and subsequent triflation of the hydroxy group was developed.     

Kinetic and thermodynamic characterization of camptothecin hydrolysis at physiological pH in the absence and presence of human serum albumin

To accurately derive the kinetic and thermodynamic parameters governing the hydrolysis of the lactone ring at physiological pH, a derivative spectrophotometric technique was used for the simultaneous estimation of lactone and carboxylate forms of camptothecin (CPT). The hydrolysis of the CPT‐lactone and the lactonization of CPT‐carboxylate at 310.15 K followed a first‐order decay with apparent rate constants equal to 0.0279 ± 0.0016 min^?1 and 0.0282 ± 0.0024 min^?1, respectively. The activation energy associated with the hydrolysis of the CPT‐lactone and the lactonization of the CPT‐carboxylate as calculated from the Arrhenius equation was 89.18 ± 0.84 and 86.49 ± 2.7 kJ mol^?1, respectively. The enthalpy and entropy of the thermodynamically favored hydrolysis reaction were on average 10.49 kJ mol^?1 and 48.00 J K^?1 mol^?1, respectively. The positive enthalpy and entropy values of the CPT‐lactone hydrolysis indicate that the reaction is endothermic and entropically driven. The stability of CPT‐lactone in the presence of human serum albumin (HSA) was also analyzed. Notwithstanding the much faster hydrolysis of the CPT‐lactone in the presence of HSA at various temperatures, the energy of activation was determined to be similar to the one estimated in the absence of HSA, suggesting that HSA does not catalyze the hydrolysis reaction, but it merely binds, sequesters, and stabilizes the CPT‐carboxylate species. © 2009 Wiley Periodicals, Inc. Int J Chem Kinet 41: 704–715, 2009     

Nitro-substituted stilbeneboronate pinacol esters and their fluoro-adducts. Fluoride ion induced polarity enhancement of arylboronate esters

A series of stilbeneboronate pinacol cyclic esters, containing none to three nitro groups, have been synthesized by various olefination reactions and characterized by X-ray single-crystal structure analysis. A stilbeneboronate ester bearing electron-acceptor groups experiences transition to a push-pull pi-electron system upon complexation with one fluoride ion at the boron atom. The UV-vis absorption maxima of the presented nitro-substituted stilbeneboronate esters are red-shifted upon addition of fluoride ions, indicating this binding event. The enhancement of the polarity of the investigated compounds and the changes in the electronic system were investigated by UV-vis absorption spectroscopy and solvatochromism. Additionally, studies were performed by natural bond orbital (NBO) analysis and RI-CC2 calculations of the vertical excitation energies. The synergism of fluoride ion complexation and solvation upon the UV-vis band shift is interpreted in terms of linear solvation energy relationships (LSERs) using the Kamlet-Taft solvent parameter set. It is found that the UV-vis absorption of the fluoro-boronates is strongly dependent on the solvents hydrogen-bond donating ability.     

Preparation and Suzuki-Miyaura coupling reactions of tetrahydropyridine-2-boronic acid pinacol esters

[reaction: see text] A study on the conversion of lactam-derived vinyl triflates and phosphates into the corresponding vinyl boronates was carried out. While delta-valerolactam-derived vinyl triflates were successfully converted into 1,4,5,6-tetrahydropyridine-2-boronic acid pinacol ester derivatives by Pd-catalyzed coupling reaction with both bis(pinacolato)diboron and pinacolborane, pyrrolidinone and epsilon-caprolactam derivatives either did not react or were readily reduced. The delta-valerolactam-derived vinyl boronates are thermally stable compounds that efficiently coupled, under Pd catalysis, with structurally diverse aryl and heteroaryl bromides and triflates, vinyl iodides and bromides, and aromatic acid chlorides, to give the corresponding 2-substituted piperidines in good to excellent yields. The number of electrophiles that can virtually be coupled with these new boronic esters makes them very useful reagents for the synthesis of N-heterocyclic compounds.     

2-二氟甲氧(硫)基吡啶-5-硼酸频哪醇酯类化合物的合成

以吡啶类化合物作为起始原料,先经二氟甲基化反应在羟基或巯基上引入二氟甲基基团,再用铱催化剂活化吡啶环的C-H并直接引入硼酸频哪醇酯基团,得到目标化合物,其产物结构经1 H NMR、13 C NMR、MS和元素分析确证.该方法具有合成路线较短、反应条件温和、原料廉价易得以及产率较高等优点.     

Ratiometric fluorescent chemosensor for silver ion at physiological pH

Bis-pyrene derivative 1, bearing two pyrene and pyridine groups, was synthesized as a ratiometric fluorescent chemosensor for Ag(+) in aqueous solution. Fluorescent chemosensor 1 displayed a selective ratiometric change with Ag(+), which was attributed to the excimer-monomer emissions of pyrenes. A mechanism for the binding mode was proposed based on fluorescence changes, NMR experiments, and theoretical calculations.     

Anti-viral cyclam macrocycles : rapid zinc uptake at physiological pH

NMR and UV-vis spectroscopic studies show that Zn(II) binds to cyclam rapidly at micromolar concentrations, an observation relevant to the anti-viral activity and co-receptor binding of anti-HIV cyclams.     

Spectroscopic analysis on the resveratrol-DNA binding interactions at physiological pH

The interaction of resveratrol with calf thymus deoxyribonucleic acid (ctDNA) under physiological conditions (Tris–HCl buffer solutions, pH 7.4) was studied by spectroscopy, fluorescence spectroscopy and viscosity measurement method, respectively. Results indicated that a complex of resveratrol with ctDNA was formed with a binding constant of K_{17 °C} = 5.49 × 10³ L mol⁻¹ and K_{37 °C} = 1.90 × 10⁴ L mol⁻¹. The fluorescence quenching mechanism of acridine orange (AO)-ctDNA by resveratrol was shown to be a static quenching type. The thermodynamic parameters of the complex were calculated by a double reciprocal method: , and (37 °C). Spectroscopic techniques together with viscosity determination provided evidences of intercalation mode of binding for the interaction between resveratrol and ctDNA.     

Kinetic and thermodynamic analysis of 9‐nitrocamptothecin hydrolysis at physiological pH in the presence and absence of human serum albumin

Kinetic and thermodynamic analysis of the 9‐nitrocamptothecin (9NC) hydrolysis reaction in the presence and absence of human serum albumin (HSA) in phosphate‐buffered saline (PBS) of pH 7.4 was carried out by first derivative absorption spectroscopy. The thermodynamic parameters determined in these studies provided a mechanistic explanation toward the endothermic but yet thermodynamically favorable hydrolysis of 9NC at physiological temperature and pH. In the presence of HSA, the apparent rate constant of 9NC hydrolysis was 3–3.5 times higher than in 9NC solutions alone, whereas the apparent equilibrium constant of 9NC hydrolysis was found to increase at a higher extent in the presence of HSA than in PBS with increasing temperature, reaching almost complete hydrolysis of the 9NC to the 9NC‐carboxylate at 315.15 K. Importantly, the E_a of the 9NC hydrolysis reaction in the presence of HSA was determined to be on average 17 kJ mol^?1 lower than the E_a determined in plain PBS. Moreover, analysis of binding isotherms constructed for the HSA interaction with 9NC, using infinitely cooperative and independent binding models, demonstrated an incredibly higher binding constant for the 9NC‐carboxylate form as compared to the very weak and concentration‐dependent binding for the 9NC‐lactone species at 310.15 K. Taken together, the preferential association of the carboxylate form with HSA and the lower E_a of 9NC hydrolysis in the presence of HSA provide a mechanistic explanation for the shift of lactone–carboxylate equilibria toward the carboxylate product under physiological conditions of pH and ionic strength. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 693–703, 2010     

Asymmetric synthesis of new bicyclic phenylboronic esters containing configurationally stable chiral nitrogen and boron

The reaction between phenylboronic acid and N-alkyl-N-(ethyl-2-hydroxy)-aminoacetic acids leads stereoselectively to stable bicyclic esters containing chiral boron and nitrogen atoms.     

Catalytic hydrolysis of phosphate esters in microemulsions

We have continued our kinetics investigation of the iodosobenzoate (IBA) catalysis of the hydrolysis of p-nitrophenyl diphenyl phosphate (PNDP), in microemulsion media composed of hexadecane in water stabilized by cetyltrimethylammonium bromide and 1-butanol over a range of water mass fractions. We have examined two iodosobenzoic acid derivatives (5-nitro-2-iodosobenzoic acid and 5-octyloxy-2-iodosobenzoic acid) as catalysts. In addition, we have determined by³¹P FT-NMR techniques that the major product of the hydrolysis of PNDP, both in IBA catalyzed and in uncatalyzed media, is diphenylphosphate.     

New 1H-pyrazole-containing polyamine receptors able to complex L-glutamate in water at physiological pH values

The interaction of the pyrazole-containing macrocyclic receptors 3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.1(11,14)]-octacosa-1(27),11,14(28),24-tetraene 1[L1], 13,26-dibenzyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.1(1)(1,14)]-octacosa-1(27),11,14(28),24-tetraene 2[L2], 3,9,12,13,16,22,25,26-octaazatricyclo-[22.2.1.1(11,14)]-octacosa-1(27),11,14(28),24-tetraene 3[L3], 6,19-dibenzyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.1(11,)(14)]-octacosa-1(27),11,14(28),24-tetraene 4[L4], 6,19-diphenethyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.1(11,14)]-octacosa-1(27),11,14(28),24-tetraene 5[L5], and 6,19-dioctyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.1(11,14)]-octacosa-1(27),11,14(28),24-tetraene 6[L6] with l-glutamate in aqueous solution has been studied by potentiometric techniques. The synthesis of receptors 3-6[L3-L6] is described for the first time. The potentiometric results show that 4[L4] containing benzyl groups in the central nitrogens of the polyamine side chains is the receptor displaying the larger interaction at pH 7.4 (Keff = 2.04 x 10(4)). The presence of phenethyl 5[L5] or octyl groups 6[L6] instead of benzyl groups 4[L4] in the central nitrogens of the chains produces a drastic decrease in the stability [Keff = 3.51 x 10(2) (5), Keff = 3.64 x 10(2) (6)]. The studies show the relevance of the central polyaminic nitrogen in the interaction with glutamate. 1[L1] and 2[L2] with secondary nitrogens in this position present significantly larger interactions than 3[L3], which lacks an amino group in the center of the chains. The NMR and modeling studies suggest the important contribution of hydrogen bonding and pi-cation interaction to adduct formation.     

Unprecedented acceleration of zirconium(IV)-assisted peptide hydrolysis at neutral pH

4,13-Diaza-18-crown-6 substantially increases the rate of zirconium(IV) hydrolysis of unactivated peptide amide bonds under near-physiological conditions of temperature and pH. In the presence of this azacrown ether, ZrCl(4) efficiently hydrolyses both neutral and negatively charged peptides (pH 7.0-7.3, 37-60 degrees C).     

Synthesis and hydrolysis of 5-nitrofurandicarboxylic acid esters

A method of the hydrolysis of 5-nitrofurandicarboxylic acid testers is proposed. The difference in the reactivities of the ester groups attached to the furan ring and in the side chain is explained by the effect of steric factors. It is shown that the direction of hydrolysis is determined by the structure of the alkyl substituent in the ester group. The mechanisms of the hydrolysis are discussed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 311–313, March, 1977.     

Intramolecular general base catalyzed ester hydrolysis. The hydrolysis of 2-aminobenzoate esters

Rate constants have been obtained for the hydrolysis of the trifluoroethyl, phenyl, and p-nitrophenyl esters of 2-aminobenzoic acid at 50 degrees C in H(2)O. The pseudo-first-order rate constants, k(obsd), are pH independent from pH 8 to pH 4 (the pK(a) of the amine group conjugate acid). The 2-aminobenzoate esters hydrolyze with similar rate constants in the pH-independent reactions, and these water reactions are approximately 2-fold slower in D(2)O than in H(2)O. The most likely mechanism involves intramolecular general base catalysis by the neighboring amine group. The rate enhancements in the pH-independent reaction in comparison with the pH-independent hydrolysis of the corresponding para substituted esters or the benzoate esters are 50-100-fold. In comparison with the hydroxide ion catalyzed reaction, the enhancement in k(obsd) at pH 4 with the phenyl ester is 10(5)-fold. Intramolecular general base catalyzed reactions are assessed in respect to their relative advantages and disadvantages in enzyme catalysis. A general base catalyzed reaction can be more rapid at low pH than a nucleophilic reaction that has a marked dependence on pH and the leaving group.