Thermochemical studies on 3-methyl-quinoxaline-2-carboxamide-1,4-dioxide derivatives: enthalpies of formation and of N-O bond dissociation

The standard molar enthalpies of formation of the 3-methyl-N-R-2-quinoxalinecarboxamide-1,4-dioxides (R = H, phenyl, 2-tolyl) in the gas phase were derived using the values for the enthalpies of combustion of the crystalline compounds, measured by static bomb combustion calorimetry, and for the enthalpies of sublimation, measured by Knudsen effusion, at T = 298.15 K. These values have also been used to calibrate a computational procedure that has been employed to estimate the gas-phase enthalpies of formation of the corresponding 3-methyl-N-R-2-quinoxalinecarboxamides and also to compute the first, second, and mean N-O bond dissociation enthalpies in the gas phase. It is found that the size of the substituent almost does not influence the computed N-O bond dissociation enthalpies; the maximum enthalpic difference is approximately 5 kJ.mol-1.     

Critical re-evaluation of the O-H bond dissociation enthalpy in phenol

The gas-phase O-H bond dissociation enthalpy, BDE, in phenol provides an essential benchmark for calibrating the O-H BDEs of other phenols, data which aids our understanding of the reactivities of phenols, such as their relevant antioxidant activities. In a recent review, the O-H BDE for phenol was presented as 90 +/- 3 kcal mol(-1) (Acc. Chem. Res. 2003, 36, 255-263). Due to the large margin of error, such a parameter cannot be used for dynamic interpretations nor can it be used as an anchor point in the development of more advanced computational models. We have reevaluated the existing experimental gas-phase data (thermolyses and ion chemistry). The large errors and variations in thermodynamic parameters associated with the gas-phase ion chemistry methods produce inconsistent results, but the thermolytic data has afforded a value of 87.0 +/- 0.5 kcal mol(-1). Next, the effect of solvent has been carefully scrutinized in four liquid-phase methods for measuring the O-H BDE in phenol: photoacoustic calorimetry, one-electron potential measurements, an electrochemical cycle, and radical equilibrium electron paramagnetic resonance (REqEPR). The enthalpic effect due to solvation, by, e.g., water, could be rigorously accounted for by means of an empirical model and the difference in hydrogen bond interactions of the solvent with phenol and the phenoxyl radical. For the REqEPR method, a second correction is required since the calibration standard, the O-H BDE in 2,4,6-tri-tert-butylphenol, had to be revised. From the gas-phase thermolysis data and three liquid-phase techniques (excluding the electrochemical cycle method), the present analysis yields a gas-phase BDE of 86.7 +/- 0.7 kcal mol(-1). The O-H BDE was also estimated by state-of-the-art computational approaches (G3, CBS-APNO, and CBS-QB3) providing a range from 86.4 to 87.7 kcal mol(-1). We therefore recommend that in the future, and until further refinement is possible, the gas-phase O-H BDE in phenol should be presented as 86.7 +/- 0.7 kcal mol(-1).     

Novel 2-amino-3-(2,4-dinitrophenylamino) derivatives of 1,4-naphthoquinone

The strong electron withdrawing nature of a 2,4-dinitrophenylamino group when attached to a chloro-naphthoquinone enhances the displacement of the chlorine atom by various aliphatic, cyclic and aromatic amines. A new series of 2-amino-3-(2,4-dinitrophenylamino) derivatives of 1,4-naphthoquinone were prepared. Three absorption maxima in the UV-vis spectra were typical, including one at 430-550 nm assigned to a CT transition.     

3-amino-1,2,4-benzotriazine 4-oxide: characterization of a new metabolite arising from bioreductive processing of the antitumor agent 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine).

Tirapazamine (1) is a promising antitumor agent that selectively causes DNA damage in hypoxic tumor cells, following one-electron bioreductive activation. Surprisingly, after more than 10 years of study, the products arising from bioreductive metabolism of tirapazamine have not been completely characterized. The two previously characterized metabolites are 3-amino-1,2,4-benzotriazine 1-oxide (3) and 3-amino-1,2,4-benzotriazine (5). In this work, 3-amino-1,2,4-benzotriazine 4-oxide (4) is identified for the first time as a product resulting from one-electron activation of the antitumor agent tirapazamine by the enzymes xanthine/xanthine oxidase and NADPH:cytochrome P450 oxidoreductase. As part of this work, the novel N-oxide (4) was unambiguously synthesized and characterized using NMR spectroscopy, UV-vis spectroscopy, LC/MS, and X-ray crystallography. Under conditions where the parent drug tirapazamine is enzymatically activated, the metabolite 4 is produced but readily undergoes further reduction to the benzotriazine (5). Thus, under circumstances where extensive reductive metabolism occurs, the yield of the 4-oxide (4) decreases. In contrast, the isomeric two-electron reduction product 3-amino-1,2,4-benzotriazine 1-oxide (3) does not readily undergo enzymatic reduction and, therefore, is found as a major bioreductive metabolite under all conditions. Finally, the ability of the 4-oxide metabolite (4) to participate in tirapazamine-mediated DNA damage is considered.     

Activation of 3-amino-1,2,4-benzotriazine 1,4-dioxide antitumor agents to oxidizing species following their one-electron reduction

The mechanism by which a benzotriazine 1,4-dioxide class of anticancer drugs produce oxidizing radicals following their one-electron reduction has been investigated using tirapazamine (3-amino-1,2,4-benzotriazine 1,4-dioxide, 1) and its 6-methoxy (6), 7-dimethylamino (7), and 8-methyl (8) analogues. By measuring the changes in absorption with pH, we found that the radical anions undergo protonation with radical pK(r) values of 6.19 +/- 0.05, 6.10 +/- 0.03, 6.45 +/- 0.04, and 6.60 +/- 0.04, respectively. The one-electron reduced species underwent a first-order reaction, with increased rate constants from 112 +/- 23 s(-)(1) for 1 to 777 +/- 12 s(-)(1)(6), 1120 +/- 29 s(-)(1) (7), and 825 +/- 89 s(-)(1) (8) at pH 7. No overall change in conductance was observed following the one-electron reduction of 6, and 8 at pH 4.5, consistent with the protonation of the radical anions, but a loss in conductance was seen for one-electron reduced 7 because of further protonation of the initially formed radical. This is assigned to the protonation of the dimethylamino group of the radical species, which has a pK(a) of 8.8 +/- 0.3. All conductance changes take place on a time-scale shorter than those of the above first-order reactions, which are not associated with the formation or loss of charged species. The absorption spectra present at the end of the unimolecular reactions were found to be similar to those formed immediately upon the one-electron oxidation of the respective substituted 3-amino-1,2,4-benzotriazine 1-oxides, and it is suggested that common benzotriazinyl radicals are formed by both routes. All these intermediate radicals underwent dismutation to produce final spectra matched by equal contributions of the parent compound and their respective substituted 3-amino-1,2,4-benzotriazine 1-oxides. By establishing redox equilibria between the intermediate radicals formed on the one-electron oxidation of the respective 3-amino-1,2,4-benzotriazine 1-oxides of the compounds and reference compounds, we found the one-electron reduction potential of the oxidizing radicals to range from 0.94 to 1.31 V. The benzotriazinyl radical of tirapazamine was found to oxidize dGMP and 2-deoxyribose with rate constants of (1.4 +/- 0.2) x 10(8) M(-)(1) s(-)(1) and (3.7 +/- 0.5) x 10(6) M(-)(1) s(-)(1), respectively.     

Thermal decomposition of 2-amino-3-aziridino-1,4-naphthoquinones

The course of the thermal decomposition of various 2-amino-3-substituted aziridino-1,4-naphthoquinones (Ia-g) was investigated. In all the cases, the thermal decomposition gave variable amounts of 2,3-diamino-1,4-naphthoquinone (II) and of substituted 1,2,3,4,5,10-hexahydrobenzo[g]quinoxaline-5,10-diones (IIIa-g) with complete stereospecificity. The decomposition of the aziridines Ib,f also gave significative amounts of 2-amino-3-allylamino-1,4-naphthoquinones (IVb,f). In the case of 2-amino-3-(2′-phenyl-3′-ethylaziridino)-1,4-naphthoquinone (Ig), the formation of trans-1-phenyl-1-butene (V), 2-(1-phenylpropyl)-1H-naphtho-imidazole-4,9-dione (VI), 2-phenyl-3-ethyl-3,4,5,10-tetrahydrobenzo[g]quinoxaline-5,10-dione (VII), 2-phenyl-3-ethyl-5,10-dihydrobenzo[g]quinoxaline-5,10-dione (VIII), and a mixture of cis- and trans-4H-2,3,5,6-tetra-hydro-2-phenyl-3-ethyl-5-iminonaphtho[1,2-b]oxazin-6-one (IX) also occurred. Hypotheses concerning the mechanism and the steric course of this reaction are given. The reaction is a general method for the stereospecific synthesis of 2,3-disubstituted 1,2,3,4,5,10-hexahydrobenzo[g]quinoxalines.     

Calorimetric and computational study of 1,4-dithiacyclohexane 1,1-dioxide (1,4-dithiane sulfone)

This work reports the enthalpies of formation in the condensed and gas state of 1,4-dithiacyclohexane 1,1-dioxide (1,4-dithiane sulfone, 5), derived from the enthalpy of combustion in oxygen, measured by a rotating bomb calorimeter and the variation of vapor pressures with temperatures determined by the Knudsen effusion technique. The theoretically estimated enthalpy of formation was calculated from high-level ab initio molecular orbital calculations at the G2(MP2) level. The theoretical calculations appear to be in very good agreement with experiment. A comparison of the conversion of thiane sulfone 3 to 1,3-dithiane sulfone 4 and 1,4-dithiane sulfone 5 clearly shows the 1,3 isomer to be 6.7 kJ mol(-1) less stable, probably owing to diminished electrostatic repulsion between the sulfur heteroatoms in 1,4-sulfone 5.     

Synthesis of novel spiro-condensed 2-amino-4H-pyrans based on 1,2-benzoxathiin-4(3H)-one 2,2-dioxide

Chemistry of Heterocyclic Compounds - A series of new spiro-condensed 2-amino-4H-pyrans were synthesized by three-component interaction of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide, malononitrile, and...     

Synthesis of 2H-1,4-thiazin-3(4H)-one 1-oxide and 2H-1,4-thiazin-3-(4H)-one 1,1-dioxide,structural analogs of uracil

The synthesis of 1,4-thiazine 1-oxide and 1,1-dioxide analogs of the antibiotic emimycin is described. Reaction of methylthioglycolate with 1-bromo-2,2-diethoxyethane gave methyl (2,2-diethoxyethylthio)acetate ( 2 ). Treatment of 2 with methanolic ammonia followed by cyclization furnished 2H-1,4-thiazin-3(4H)-one ( 5 ). Oxidation of 5 with m-chloroperoxybenzoic acid converted it to 2H-1,4-thiazin-3(4H)-one 1-oxide ( 6 ). Oxidation of 2 with potassium permanganate, followed by treatment with methanolic ammonia, and cyclization gave 2H-1,4-thiazin-3(4H)-one 1,1-dioxide.     

三元配合物Tb(Et2dtc)3(phen)的热化学性质

以铜试剂(NaEt2dtc•3H2O)和邻菲咯啉(o-phen•H2O) 与水合氯化铽(TbCl3•3.75H2O)在无水乙醇中制得了三元固态配合物.化学分析和元素分析确定其组成为Tb(Et2dtc)3(phen).IR光谱研究表明配合物中Tb3＋与NaEt2dtc中的硫原子双齿配位,同时与phen的氮原子双齿配位.用Calvet微热量计测定了298.15 K下液相生成反应的焓变ΔrHmθ(l),为(－21.819±0.055) kJ•mol－1,通过热化学循环计算了固相生成反应焓变ΔrHmθ(s),为(128.476±0.675) kJ•mol－1.改变反应温度,研究了液相生成反应的热动力学.用精密转动弹热量计测得配合物的恒容燃烧能ΔcU为(－17646.95±8.64) kJ•mol－1,经计算其标准燃烧焓ΔcHHmθ和标准生成焓ΔfHmθ分别为(－17666.16±8.64) kJ•mol－1和(－1084.04±9.49) kJ•mol－1.     

Thermochemistry of the Ternary Complex Nd（Et2dtc）3（phen）

Introduction A series of lanthanide sulfide complexes have beenlargely used for ceramics and thin film materials1 andthese complexes could be prepared from the precursorswhich are the compounds containing lanthanide-sulfurbonds.2-4 For instance, the compounds synthesized with[(alkyl)2dtc]-, phen?H2O and lanthanide salts were usedas the volatile precursors for preparing lanthanide sul-fide, its friction properties in lubricant was investigatedin literature 5 and the preparation and propertie…     

Syntheses, Crystal Structures and Fluorescence of Cadmium(Ⅱ) Coordination Polymers with Pyrazine-1,4-dioxide, 2-Methylpyrazine-1,4-dioxide and Thiocyanate as Mixed Bridge Ligands

Two Cd(Ⅱ) coordination polymers have been synthesized with pyrazine-1,4-dioxide(L1), 2-methylpyrazine-1,4-dioxide (L2), and thiocyanate anion as mixed bridge ligands. Crystal data for complex 1 [Cd(μ13-SCN-)2(L1)]n: monoclinic system, space group P21/n with a =6.8342(11), b = 14.349(2), c = 10.5443(16) (A), β = 98.534(2)°, V = 1022.5(3) (A)3, Z = 4,C6H4CdN4O2S2, Mr = 340.65, Dc. = 2.213 g/cm3, F(000) = 656 andμ = 2.527 mm-1; and those for2: triclinic system, space group P1 with a = 7.877(3), b = 8.693(3), c = 8.754(3) (A), α =102.297(6), β= 102.464(6), γ= 98.480(6)°, V = 560.0(3) (A)3, Z = 2, C7H6CdN4O2S2, Mr = 354.68,Dc = 2.103 g/cm3, F(000) = 344 and μ = 2.311 mm-1. 1 shows a three-dimensional network structure, and along the c direction a one-dimensional chain is constructed by the coordination of Cd(Ⅱ) ions withμ1,3-SCN- ligands, and the L1 bridging ligands made the chains connect each other leading to the formation of a three-dimensional structure. For 2, the one-dimensional chains along the b axis are generated by the coordination of L2 bridging ligands with Cd(Ⅱ) ions, and the chains are further joined byμ1,3-SCN- bridging ligands forming a two-dimensional sheet structure on the (1 0 -1) plane. Both complexes 1 and 2 exhibit strong fluorescence emission.