PHOTOLYSIS AND RADIOLYSIS OF PHENYL-ALANYLGLYCINE

T he P hotolysis of glycine and alanine containing peptides in oxygenated solution has been shown to result in the formation of glyoxylic and pyruvic acids, through oxidative cleavage of the peptide bond[1]. The same products were formed in the radiolysis of such peptides in the presence of oxygen[2]. In a peptide containing aromatic amino-acids the absorption of light results in the excitation of the aromatic ring and it has been postulated[3] that energy is transferred to the peptide bond, resulting in the formation of a radical on the carbon atom adjacent to the peptide bond. Radiolysis, however, involves the attack of hydroxyl radicals and other reactive species formed in the absorption of radiation by water[2]. This study compares the behavior of phenylalanylglycine to photolysis and radiolysis in aerated aqueous solution in relation to a possible energy transfer in photolysis.     

Generation and metathesis of azomethine imines in reaction of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with het(aryl)methylidenemalononitriles

A new metathesis reaction of azomethine imines is found. Catalytic or thermal diaziridine ring opening of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes leads to azomethine imines reacting further with het(aryl)methylidenemalononitriles to give in situ new azomethine imines inaccessible by common synthetic methods. New azomethine imines are detected as pyrazolines formed via a 1,4-H shift and trapped by the [3+2] cycloaddition with various dipolarophiles to yield 1,5-diazabicyclo[3.3.0]octane derivatives bearing pharmacophoric heterocycles, e.g. furan, nitrofuran, thiophene, and indole. The best results are achieved in the Et₂O·BF₃-catalyzed reactions in ionic liquids.     

Ethynylation of 2-(furan-2-yl)- and 2-(thiophen-2-yl)pyrroles with acylbromoacetylenes in the Al2O3 medium: relative reactivity of heterocycles

2-(Furan-2-yl)- and 2-(thiophen-2-yl)pyrroles are readily ethynylated with acylbromoacetylenes in the solid Al₂O₃ medium (no solvent, room temperature, 1 h) to afford 5-(furan-2-yl)- and 5-(thiophen-2-yl)-2-acylethynylpyrroles in 39–74% yields. In the case of 2-(furan-2-yl)pyrroles, an alternative ethynylation of the furan ring takes place, the ratio of the furan and pyrrole ring ethynylation products being 1:5–7. No ethynylation of the thiophene ring as well as ethynylation of both heterocycles in a one molecule has been detected. Thus the reactivity of the heterocycles towards the ethynylation system (acylbromoacetylenes/Al₂O₃) falls in the order: pyrrole>furan>thiophene.     

Quinolone analogues 7 [1‐6]. Synthesis of 3‐Heteroaryl‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones

The 3‐heteroaryl‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones 6a‐e were synthesized by the oxidative‐hydrolytic ring transformation of the 3‐heteroaryl‐1,2‐diazepino[3,4‐b]]quinoxaline‐5‐carbonitriles 9a‐c , which were obtained by the 1,3‐dipolar cycloaddition reaction of the 2‐(2‐heteroarylmethylene‐1‐methylhydrazino)quinoxaline 4‐oxides with 2‐chloroacrylonitrile. The assignment of the thiophene and furan ring protons was carried out through the data of the NOE, decoupling, and coupling constants.     

Kinetics of the reactions of O3 and OH radicals with furan and thiophene at 298 ± 2 K

Rate constants for the reactions of O₃ and OH radicals with furan and thiophene have been determined at 298 ± 2 K. The rate constants obtained for the O₃ reactions were (2.42 ± 0.28) × 10^?18 cm³/molec·s for furan and <6 ×10^?20 cm³/molec·s for thiophene. The rate constants for the OH radical reactions, relative to a rate constant for the reaction of OH radicals with n-hexane of (5.70 ± 0.09) × 10^?12 cm³/molec·s, were determined to be (4.01 ± 0.30) × 10^?11 cm³/molec·s for furan and (9.58 ± 0.38) × 10^?12 cm³/molec·s for thiophene. There are to date no reported rate constant data for the reactions of OH radicals with furan and thiophene or for the reaction of O₃ with furan. The data are compared and discussed with respect to those for other alkenes, dialkenes, and heteroatom containing organics.     

The radiation chemistry of acyclic hydrofluoro and perhalogenated ether and hydrocarbon compounds

The radiolytic stability of some hydrofluoroethers and hydrofluorocarbons was investigated and compared with those of perfluoropolyethers (PFPEs) and the CCl₂FCClF₂ (CFC 113). The experimental results indicate that stability depends mainly on the relative abundance of hydrogen atoms in the molecule; however, a significant role is played also by the chemical structure (i.e. the relative positions of the hydrogen atoms in the molecule). As a result, molecules containing hydrogen atoms as OCF₂H chain ends show a higher stability compared with the other hydrofluoro compounds. Based on the analysis of the end products and on the nature of radicals detected by EPR, radiolysis mechanisms are proposed and discussed. Due to their high dipole moments the hydrofluoro compounds and CCl₂FCClF₂ degrade mainly through an ionic mechanism.     

C?H Bond Activation/Borylation of Furans and Thiophenes Catalyzed by a Half‐Sandwich Iron N‐Heterocyclic Carbene Complex

A coordinatively unsaturated iron‐methyl complex having an N‐heterocyclic carbene ligand, [Cp*Fe(L^Me)Me] ( 1 ; Cp*=η⁵‐C₅Me₅, L^Me=1,3,4,5‐tetramethyl‐imidazol‐2‐ylidene), is synthesized from the reaction of [Cp*Fe(TMEDA)Cl] (TMEDA=N,N,N′,N′‐tetramethylethylenediamine) with methyllithium and L^Me. Complex 1 is found to activate the C? H bonds of furan, thiophene, and benzene, giving rise to aryl complexes, [Cp*Fe(L^Me)(aryl)] (aryl=2‐furyl ( 2 ), 2‐thienyl ( 3 ), phenyl ( 4 )). The C? H bond cleavage reactions are applied to the dehydrogenative coupling of furans or thiophenes with pinacolborane (HBpin) in the presence of tert‐butylethylene and a catalytic amount of 1 (10 mol % to HBpin). The borylation of the furan/thiophene or 2‐substituted furans/thiophenes occurs exclusively at the 2‐ or 5‐positions, respectively, whereas that of 3‐substituted furans/thiophenes takes place mainly at the 5‐position and gives a mixture of regioisomers. Treatment of 2 with 2 equiv of HBpin results in the quantitative formation of 2‐boryl‐furan and the borohydride complex [Cp*Fe(L^Me)(H₂Bpin)] ( 5 ). Heating a solution of 5 in the presence of tert‐butylethylene led to the formation of an alkyl complex [Cp*Fe(L^Me)CH₂CH₂tBu] ( 6 ), which was found to cleave the C? H bond of furan to produce 2 . On the basis of these results, a possible catalytic cycle is proposed.     

Bond dissociations in hypervalent ammonium radicals prepared by collisional neutralization of protonated six-membered nitrogen heterocycles

Hypervalent organic ammonium radicals were generated by collisional neutralization with dimethyl disulfide of protonated 1,4-diazabicyclo[2.2.2]octane (1H⁺), N,N′-dimethylpiperazine (2H⁺) and N-methylpiperazine (3H⁺). The radicals dissociated completely on the 5.1 μs time-scale. Radical 1H^• underwent competitive N−H and N−C bond dissociations producing 1,4-diazabicyclo[2.2.2]octane and small ring fragments. Dissociations of radical 2H^• proceeded by N−H bond dissociation and ring cleavage, whereas N−CH₃ bond cleavage was less frequent. Radical 3H^• underwent N−H, N−CH₃ and N−C_ring bond cleavages followed by post-reionization dissociations of the formed cations. The pattern of bond dissociations in the hypervalent ammonium radicals derived from six-membered nitrogen heterocycles is similar to those of aliphatic ammonium radicals. © 1997 John Wiley & Sons, Ltd.     

Cyclisation radicalaire de la desoxy-2′-adenosine en solution aqueuse,sous l'effet du rayonnement gamma

5′,8-Cyclo-2′-deoxy-adenosine 2 has been identified as one of the principal products of gamma radiolysis of 2′-deoxyadenosine (G = 0.03 in the presence of oxygen; G = 0.05 in the absence of oxygen). This compound is likely to play a role in the phenomena of radio-induced mutation. ¹H-NMR studies at 250 MHz have shown the remarkable geometry of the compound since three coupling constants of the vicinal protons of the sugar fragment have not been detected. The study of the model has in fact shown that the corresponding protons form an angle close to 90°. The formation of 2 shows that the C8-N7 double bond is attacked by the radical on the carbon 5′ of 1, produced by the action of OH· radicals formed by the radiolysis of water.     

黄酮类化合物与α-羟乙基过氧自由基反应的脉冲辐解研究

由于脂质过氧化反应(LPO)是导致人体疾病(如肝炎、肝硬化、动脉硬化、脑溢血等)的主要原因, 而黄酮类化合物是一类很强的过氧化反应抑制剂, 因此有必要研究其化学结构与过氧化反应的关系及其抗氧化机理.本文选择α-羟乙基过氧自由基为脂质过氧自由基的模拟物, 采用脉冲辐解方法研究了乙醇溶液中4种典型的黄酮类化合物(槲皮素、芦丁、儿茶素以及黄岑甙)与α-羟乙基过氧自由基的反应动力学, 测得其反应活性顺序为:芦丁>槲皮素>黄岑甙>儿茶素. 同时以黄酮体和邻苯二酚为黄酮类化合物不同结构特征的模型化合物, 用脉冲辐解法测得二者与α-羟乙基过氧自由基的反应速率常数分别为(1.7±0.1)×10⁶和(2.9±0.1)×10⁵ mol^-1·dm³·s^-1.实验结果表明, 在黄酮类化合物与α-羟乙基过氧自由基的反应中, A环C₅位的羟基, C环C₂＝C₃或B-C环的大π键和B环邻二羟基共存时清除α-羟乙基过氧自由基活性最好, 而且C环C₂＝C₃或B-C环大π键的清除活性好于B环邻二羟基, 同时C环是否含有C₃-醣甙结构对清除作用没有明显影响. 因此我们推测在黄酮类化合物抑制脂质过氧化反应过程中, 起主要作用的是C环C₂＝C₃或B-C环的大π键与脂质过氧自由基的双键加成反应.     

Glycoside bond cleavage in the radiolysis of aqueous solutions of methylglycosides and disaccharides

The kinetics of formation of methylglycoside and disaccharide radiolysis products resulting from the O-glycoside bond cleavage was studied, and the yields of these products were determined. It was found that oxygen inhibits these processes. The findings suggest that the fragmentation reaction of C’₂ radicals plays an important role in the formation of carbohydrate degradation products in the radiolysis of aqueous carbohydrate solutions.     

Radiolysis of aqueous DCH18C6 solutions at 77 K

Low-temperature (77 K) γ- and X-ray radiolysis of aqueous DCH18C6 solutions was studied by ESR-spectroscopy. OH radicals, trapped electrons and macrocyclic radicals -CH₂-CH-O- resulting from H-atom abstraction from methylene groups of polyether ring were identified as predominant radiolysis products. Increasing the crown ether concentration in aqueous solution leads to the growth of relative yields of the trapped electron and macrocyclic radicals as well as the decrease of that of hydroxyl radical. Neither radical products of macrocycle rupture nor H-atom abstraction from cyclohexane rings were observed.     

Stability of [MeBu3N][Tf2N] under gamma irradiation

The stability of the ionic liquid [MeBu3N][Tf2N], dry or after contact with water (where [MeBu3N]+ is the methyltributylammonium cation and [Tf2N](-) is the bistriflimide anion), was studied under 137Cs gamma irradiation in argon and in air. In a quantitative study with an absorbed dose of 2 MGy this ionic liquid was highly stable regardless of the radiolysis conditions. The radiolytic disappearance yields determined by ESI-MS were -0.38 and -0.25 micromol J(-1) for the cation and anion, respectively. ESI-MS, NMR, and liquid chromatography coupled with ESI-MS identified a large number of degradation products in very small quantities for the same dose. The cation radicals were formed by the loss of a Bu group, the Me group, or two H atoms to form a double bond with the butyl chain. Radiolysis of the anion produced mainly F and CF3 radicals. The anion radicals recombined with the cation to form a wide range of secondary degradation products regardless of the radiolysis conditions.     

Radiolysis of iodotyrosines in aqueous-ethanol solutions

⁶⁰Co-gamma radiolysis of 3-iodotyrosine and 3,5-diiodotyrosine in aqueous-ethanol solutions has shown that the chemical effects are mainly determined by the interaction of radicals from the radiolysis of solvent and controlled by the composition of the solution. The influence of varying solvent composition and radiation dose on the amount of iodoamino acid converted and on the yields of the radiolysis products (I₂, I^–, IO ₃ ^– and H₂O₂) formed in aerated solutions at room termperature were investigated. The formation of I₂ is dependent upon the acidity of the solution and is mainly produced as an after-effect due to the interaction of H₂O₂ with I^– ions, both being radiolysis products. The variation of radiation-chemical yields with the solute and solvent composition, and the probable mechanisms for formation of the radiolysis products are discussed.     

Synthesis of isomeric bromo(diethoxyphosphorylmethyl)furans

Series of the previously unknown bromo(diethoxyphosphorylmethyl)furans including four of six possible regioisomers is synthesized. The target products were obtained by bromination of the corresponding (diethoxyphosphorylmethyl)furans or by a four-step synthesis including bromination of isomeric methyl-furancarboxylates, reduction of the products formed to the corresponding alcohols, substitution of hydroxy group with halogen and phosphorylation by the Michaelis-Becker reaction. It was established for the first fime that in the course of bromination of alkyl carboxylates and phosphonates of the furan series under the typical conditions of electrophilic reaction (Br₂ + 10% molar of AlCl₃, chloroform) the substituent enters not only into the heteroring, but also into the side chain. In the case of 5-methyl-2-(diethoxyphosphorylmethyl)furan only the last reaction pathway is observed. It is shown that bromo(chloromethyl)furans react with sodium diethyl phosphite not only according to the Michaelis-Becker scheme leading to phosphonates, but also by the pathway of debromination of the furan ring. The last unexpected reaction may acquire a practical use for removing a substituent protecting the α-position of the furan ring under mild conditions.     

Synthesis and Properties of 2-(2-Furyl)- and 2-(2-Thienyl)-1-methylphenanthro[9,10-d]imidazoles

Condensation of 9,10-phenanthrenequinone with 2-furaldehyde and 2-thiophenecarbaldehyde in glacial acetic acid in the presence of ammonium acetate gave 2-(2-furyl)- and 2-(2-thienyl)phenanthro[9,10-d]imidazoles which were converted into the corresponding 1-methyl derivatives. The furan and thiophene rings in the products lose their acidophobic properties. Depending on the conditions, electrophilic substitution reactions in 2-(2-furyl)- and 2-(2-thienyl)phenanthro[9,10-d]imidazoles occur both at the furan (thiophene) and phenanthrene moieties.     

Molecular rearrangements—XII: Pyrolysis of α-phenylacetanilide

Pyrolysis of α-phenylacetanilide resulted in migration of the benzyl group to the o and p positions of the aniline nucleus and formation of CO, NH₃, toluene benzaldehyde, dibenzyl, trans stilbene, aniline, 9 phenylacridine and 2,3 diphenyl-indole. With o-toluidine as a solvent the previous products were accompanied by 2,3 diphenyl-7-methylindole and 4 amino 3 methyl diphenylmethane. With isoqumoline 1 benzyl isoquinoline and 1,1' bi-isoquinolyl were also obtained.It is concluded that the pyrolysis of phenylacetanilide depends on the homolytic fission of the amide C-N bond into anilino and phenylacetyl free radicals followed by the interaction of the primary and secondary formed radicals with the rearrangement products and solvent nuclei.     

13C NMR spectra of benzo[b]thiophene and 1-(X-benzo[b]thienyl)ethyl acetate derivatives

Carbon-13 chemical shift assignments are reported for benzo[b]thiophene and 1-(X-benzo[b]thienyl)ethyl acetate derivatives, where X=? CH(OAc)CH₃ substituted at positions 2-7. Substituent chemical shift (SCS) effects for the ethyl acetate group are additive at all positions. A substantial upfield shift was observed at C-3, arising from the peri interaction of H-3 and the 4-ethyl acetate substituent. Carbon-13 relaxation times (T₁) and nuclear Overhauser enhancements (η) have been measured for benzo[b]thiophene and its derivatives, and the contributions of dipolar, T^DD₁, and spin rotation, T^SR₁, relaxation have been determined. Intramolecular dipole–dipole interactions are found to provide by far the most important spin-lattice relaxation mechanism whenever protons are bound directly to the carbons under investigation. Nonprotonated ring carbons are relaxed by both DD and SR mechanisms. Anisotropic motion has an easily observable effect on the DD contribution to T₁, and can form the basis for spectral assignments, as in 1-phenylethyl acetate. Long-range ¹³C? ¹H coupling constants were observed both between ring carbons and between ring carbons with ring side-chain hydrogens. These results have been used for the structure determination of the title compounds.     

Cation radicals of N-substituted phenothiazines

The reaction of N-substituted phenothiazines with certain acceptors (halogenated solvents CHCl₃, CH₂Br₂, CCl₄, o-chloranil, AlCl₃, SnCl₄, concentrated H₂SO₄, concentrated HNO₃ in HClO₄) has been studied by EPR spectroscopy. The hyperfine structure in the EPR spectra of the cation radicals is analyzed. To interpret the EPR spectra obtained in terms of the MNDO-PM3 method we carried out a calculation of the electronic structure of phenothiazine cation radicals containing N-CH₃ and N-CH₂R substituents. In these radical systems, there are significant steric hindrances to conformational rotation of the CH₂ substituent around the N-C bond leading to a conformation with magnetically non-equivalent protons in the methylene group.Mordovian State University, Saransk 430000. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 420–426, March, 1996. Original article submitted July 28, 1995.