Singlet oxygen oxidation of isolated and cellular DNA: product formation and mechanistic insights

This survey focuses on recent aspects of the singlet oxygen oxidation of the guanine moiety of nucleosides, oligonucleotides, isolated and cellular DNA that has been shown to be the exclusive DNA target for this biologically relevant photogenerated oxidant. A large body of mechanistic data is now available from studies performed on nucleosides in both aprotic solvents and aqueous solutions. A common process to both reaction conditions is the formation of 8-oxo-7,8-dihydroguanine by reduction of 8-hydroperoxyguanine that arises from the rearrangement of initially formed endoperoxide across the 4,8-bond of the purine moiety. However, in organic solvent the hydroperoxide is converted as a major degradation pathway into a dioxirane that subsequently decomposes into a complex pattern of oxidation products. A different reaction that involved the formation of a highly reactive quinonoid intermediate consecutively to the loss of a water molecule from the 8-hydroperoxide has been shown to occur in aqueous solution. Subsequent addition of a water molecule at C5 leads to the generation of a spiroiminodihy-dantoin compound via a rearrangement that involves an acyl shift. However, in both isolated and cellular DNA the latter decomposition pathway is at the best a minor process, because only 8-oxo-7,8-dihydroguanine has been found to be generated. It is interesting to point out that singlet oxygen has been shown to contribute predominantly to the formation of 8-oxo-7,8-dihydroguanine in the DNA of bacterial and human cells upon exposure to UVA radiation. It may be added that the formation of secondary singlet-oxygen oxidation products of 8-oxo-7,8-dihydroguanine, including spiroiminodihydantoin and oxaluric acid that were characterized in nucleosides and oligonucleotide, respectively, have not yet been found in cellular DNA.     

Acetylenedithiolate: alkyne complex formation renders it a dithiolate chelate ligand

The isostructural complexes [{Tp'W(CO)(2)(eta(2)-C(2)S(2))}(2)M] (M = Ni, Pd, Pt) show that the eta(2)-C,C'-alkyne complexes of acetylenedithiolate at [Tp'W(CO)(2)](+) can generally act as dithiolate chelate ligands, leading to dithiolene type complexes.     

Conformation as a protecting group: a regioselective aromatic bromination en route to complex pi-electron systems

A new strategy to achieve regioselective functionalization of a sterically congested aromatic system driven by conformational demands is described. Electrophilic substitution occurs at the more planarizable subunit without undesired chemistry at mutually reactive sites and without the need for protecting or masking groups that must be manipulated later. Model studies are described to understand this selectivity, and possibilities for the construction of orthogonal, differentially substituted pi-systems of relevance for molecular electronics are demonstrated.     

Oxygen dependent oxidation of trimethoprim by sulfate radical: Kinetic and mechanistic investigations

Trimethoprim (TMP) is a typical antibiotic to treat infectious disease, which is among the most commonly detected antibacterial agents in natural waters and municipal wastewaters. In the present study, the impacts of dissolved oxygen (DO) on the oxidation efficiency and pathways of TMP by reaction with sulfate radicals (SO₄⁻) were investigated. Our results revealed that the presence of DO was favourable for TMP degradation. Specifically, TMP would react initially with SO₄⁻ via electron-transfer process to form a carbon-centered radical. In the absence of oxygen, the carbon-centered radical could undergo hydrolysis to produce α-hydroxytrimethoprim (TMP−OH), followed by the further oxidation which generated α-ketotrimethoprim (TMP=O). However, in the presence of oxygen, the carbon-centered radical would alternatively combine with oxygen, leading to a sequential reaction in which peroxyl radical and a tetroxide were formed, and finally generated TMP−OH and TMP=O simultaneously. The proposed pathways were further confirmed by density functional theory (DFT) calculations. The results obtained in this study would emphasize the significance of DO on the oxidation of organic micro-pollutants by SO₄⁻.     

Kinetics and mechanism of the oxidation of some carboxylates by a nickel (III) oxime-imine complex

The kinetics of the oxidation of formate, oxalate, and malonate by |Ni^III(L¹)|²⁺ (where HL¹ = 15-amino-3-methyl-4,7,10,13-tetraazapentadec-3-en-2-one oxime) were carried out over the regions pH 3.0–5.75, 2.80–5.50, and 2.50–7.58, respectively, at constant ionic strength and temperature 40°C. All the reactions are overall second-order with first-order on both the oxidant and reductant. A general rate law is given as - d/dt|Ni^III(L¹)²⁺| = k_obs|Ni^III(L¹)²⁺| = (k_d + nk_s |R|)|Ni^III(L¹)²⁺|, where k_d is the auto-decomposition rate constant of the complex, k_s is the electron transfer rate constant, n is the stoichiometric factor, and R is either formate, oxalate, or malonate. The reactivity of all the reacting species of the reductants in solution were evaluated choosing suitable pH regions. The reactivity orders are: k_HCOOH > k; k > k > k, and k > k < k for the oxidation of formate, oxalate, and malonate, respectively, and these trends were explained considering the effect of hydrogen bonded adduct formation and thermodynamic potential. © 1997 John Wiley & Sons, Inc. Int J Chem Kinet 29: 225–230, 1997.     

Zirconium-catalyzed amine oxidation: a mechanistic study

The zirconium-catalyzed oxidation of amines in the presence of hydroperoxides gives the corresponding nitro compounds in high yields. In the present paper, we describe mechanistic details of this three-step oxidation, which was investigated by means of DFT calculations. It is shown that N-oxides, hydroxylamines, and nitroso derivatives are formed as intermediates. These compounds had already been postulated on the basis of synthetic experiments. During the oxidation process, the nitrogen atom changes its electronic character from a strong nucleophilic center to a moderate electrophilic center; this is reflected by the geometry of the transition states of the oxygen-transfer process.     

Stereochemical and mechanistic aspects of the nickel complex catalysed formation of olefins from allylic alcohols and Grignard reagents

The reaction of (+)-S-but-1-en-3-ol with phenylmagnesium bromide in the presence of bis(triphenylphosphine)nickel dichloride has been shown to proceed with inversion of configuration to yield (?)-R-3-phenylbut-1-ene.     

Multistep solution-mediated formation of AuCuSn2: mechanistic insights for the guided design of intermetallic solid-state materials and complex multimetal nanocrystals

Understanding how solids form is a challenging task, and few strategies allow for the elucidation of reaction pathways that are useful for designing new solids. Here, we describe an unusual multistep reaction pathway that leads to the formation of AuCuSn(2), a new ternary intermetallic compound that was discovered as nanocrystals using a low-temperature solution route. The formation of AuCuSn(2) using a modified polyol process occurs through a multistep pathway that was elucidated by taking aliquots throughout the course of the reaction and studying the products using a variety of techniques. The reaction proceeds through four distinct steps: (a) formation of Au nanoparticles at or near room temperature, mediated by a galvanic reaction between Au(3+) and Sn(2+) (forming Au(0) and Sn(4+), precipitated as SnO(2) that forms a shell around the nanoparticles), (b) formation of NiAs-type AuSn nanoparticles, along with Cu and Sn, upon addition of NaBH(4), (c) aggregation and thermal interdiffusion to form AuCu(x)Sn(y) alloy nanoparticles, and (d) nucleation of intermetallic AuCuSn(2), which has an ordered NiAs-derived structure. The proposed mechanism was tested by starting the reaction with the AuSn intermediate. AuSn nanoparticles were synthesized separately and reacted with Cu and Sn nanoparticles, and ordered AuCuSn(2) formed as expected. Elucidation of this reaction pathway has important implications for guiding the design of new intermetallic solids, as well as for controlling the synthesis of complex multimetal nanocrystals.     

Selective oxidations of a dithiolate complex produce a mixed sulfonate/thiolate complex

Oxygenation or peroxidation of a planar, tetracoordinate, low-spin nickel(II) complex of a N2S2-donor ligand, (N,N'-dimethyl-N,N'-bis(2-mecaptoethyl)-1, 3-propanediaminato)nickel(II), proceeds via the formation of a mixed sulfinate/thiolate complex and leads to the production of a novel dimeric complex containing both sulfonate and thiolate ligands. Thus, reaction proceeds via selective oxidation of the sulfinate sulfur atom, leaving the thiolate reduced. The novel sulfonate/thiolate complex has been isolated and characterized by electospray ionization mass spectrometry and single-crystal X-ray diffraction. Crystals form in the monoclinic space group P2(1)/c with cell dimensions a = 8.4647(12) A, b = 12.592(3) A, and c = 12.531(2) A, angles alpha = gamma = 90 degrees and beta = 106.645(11) degrees , and Z = 2. The structure was refined to R = 5.20% and R(w) = 12.86% [I > 2sigma(I)]. The isolation of this mixed sulfonate/thiolate complex from oxidation of a mixed sulfinate/thiolate complex provides experimental evidence for the formation of a sulfonate ligand via a Ni-O-O-SO2R intermediate, as suggested by recent density functional theory calculations.     

Large-scale synthesis of uniform nanotubes of a nickel complex by a solution chemical route

Novel layer-rolled nanotubes of a nickel complex have been successfully synthesized by a simple wet chemical method. The nanotubes are assembled by rolling the (111) sheets of [Ni(NH3)6]Cl2 with the assistance of a polymer. The remarkable uniformity and high yields of the nickel complex nanotubes point to future applications in various fields of nanotechnology.     

A new, higher yielding synthetic route towards dodecaphenyl cage silsesquioxanes: synthesis and mechanistic insights

Cage dodecaphenylsilsesquioxane (T12-Phenyl) was synthesized in a one batch, mildly basic aqueous solution under room temperature conditions using a trialkoxysilane precursor. Significant improvements in synthetic yield (>95%) were observed compared with previous reports. Kinetic studies of the hydrolysis of phenyltrimethoxysilane were conducted and the condensation was monitored by (29)Si NMR which revealed the presence of a transient, intermediary T1 species as the pathway to dodecaphenylsilsesquioxane spherulites, and the tendency for T12 structures over T8, T10, and other substructures was explained through MM2 simulations.     

Stereospecific cyclodehydration of 1,4-sulfanylalcohols to thiolanes: mechanistic insights

A series of thiolanes were prepared by cyclodehydration of sulfanylalcohols in the presence of catalytic amounts of p-toluenesulfonic acid or by using K10 clay. The sulfur heterocycles were synthesised in good to excellent yields using either a conventional Dean-Stark method or microwave irradiation under solvent-free conditions. The reaction could be performed regio- and stereoselectively and its mechanism was investigated by means of enantio- and diastereomerically enriched substrates. In contrast to previous studies, our results are consistent with an intramolecular S_N2-type mechanism as a general pathway.     

Singlet oxygen oxidation of 2′-deoxyguanosine. Formation and mechanistic insights

Emphasis was placed in this work on the delineation of mechanistic aspects of the singlet oxygen-mediated oxidation reactions of 2′-deoxyguanosine 1 used as a DNA model compound in aerated aqueous solution. For this purpose a thermolabile naphthalene endoperoxide derivative was used allowing the generation of [¹⁸O]-labeled singlet oxygen for dedicated mechanistic studies. The analysis and characterization of the oxidized nucleosides of the ¹O₂ reactions were achieved on the basis of accurate HPLC-tandem mass spectrometry measurements. Thus it was found that primary oxidation products include, in addition to the previously identified 8-oxo-7,8-dihydro-2′-deoxyguanosine 5 and the two diastereomers of spiroiminodihydantoin 8, two relatively minor nucleosides, namely the two diastereomers of 4-hydroxy-8-oxo-4,8-dihydro-2′-deoxyguanosine 9.     

Unprecedented polymerization of trimethylene carbonate initiated by a samarium borohydride complex: mechanistic insights and copolymerization with epsilon-caprolactone

Poly(trimethylene carbonate) (PTMC) was synthesized through ring-opening polymerization by using a rare-earth borohydride initiator, [Sm(BH(4))(3)(thf)(3)]. This initiator shows a high activity to give high-molar-mass PTMCs with molar-mass distributions ranging from 1.2 to 1.4, and with a regular structure void of ether linkages. The polymers were characterized by (1)H and (13)C NMR spectroscopy, (1)H-(1)H COSY, (1)H-(13)C HMQC NMR spectroscopy, size-exclusion chromatography (SEC), viscosimetry, and MALDI-TOF MS analyses. A coordination-insertion mechanism was established based on detailed NMR characterizations, especially of the polymer chain end-functions. The monomer initially coordinates the samarium to give [Sm(BH(4))(3)(tmc)(3)], 1. The monomer then opens up through cleavage of the cyclic ester oxygen--acyl bond and inserts into the Sm--HBH(3) bond resulting in an alkoxide complex, [Sm{O(CH(2))(3)OC(O)HBH(3)}(3)], 2, or [Sm{O(CH(2))(3)OC(O)H}(3)], 2', which then propagates the polymerization of TMC to give the active polymer [Sm({O(CH(2))(3)OC(O)}(n)O(CH(2))(3)OC(O)HBH(3))(3)], 3 or [Sm(O(CH(2))(3)OC(O){O(CH(2))(3)OC(O)}(n)O(CH(2))(3)OC(O)H)(3)], 3'. Finally, acidic hydrolysis of 3 or 3' gives HO(CH(2))(3)OC(O)[O(CH(2))(3)OC(O)](n)O(CH(2))(3)OC(O)H, 4. This novel alpha-hydroxy,omega-formatetelechelic PTMC represents the first example of a formate-terminated polycarbonate. TMC and epsilon-caprolactone (CL) were copolymerized to afford both random PTMC-co-PCL and block PTMC-b-PCL copolymers that were characterized by (1)H NMR spectroscopy, SEC, and differential scanning calorimetry (DSC). The structure of the block copolymers depends on the order of addition of monomers: if CL is introduced first, dihydroxytelechelic HO-PTMC-b-PCL-OH polymers are formed, whereas introduction of TMC first or simultaneous addition of comonomers leads to hydroxyformatetelechelic HC(O)O-PTMC-b-PCL-OH analogues.     

Electrochemical oxidation of some catechol derivatives in the presence of some betadicetone derivatives: mechanistic and thermodynamic study

Electrochemical oxidations of 4-methylcatechol (1), 4-tert-butylcatechol (5) and catechol (7) in the presence of different nucleophiles have been investigated both experimentally and theoretically. Experimental results have been obtained by means of cyclic voltammetry and controlled-potential coulometry. Also the theoretical results were calculated at DFT (B3LYP) level of theory and 6–311+G (p, d) basis set. The calculated results indicate that oxidation potential of catechols (1, 5, 7) and their substituted species are directly dependent on the ?G _tot, and continuance of reactions during electrolysis is dependent on ?G _tot of produced species on the surface of electrode. The current study indicates that theoretical studies along with empirical research can be useful in displaying electrochemical reaction mechanisms.     

A fascinating journey into history: exploration of the world of isonitriles en route to complex amides

We describe herein our recent explorations in the field of isonitrile chemistry. An array of broadly useful coupling methodologies has been developed for the formation of peptidyl and glycopeptidyl amide bonds. We further describe the application of these methods to the syntheses of complex systems, including the cyclic peptide cyclosporine A, constrained peptide systems, and heterocycles.     

Unexpected Schiff-base complex formation from the oxidation reaction of a nickel(II) complex with the meso-HMPAO ligand by molecular oxygen

The synthesis and characterization of the amine–oxime complex [Ni(meso-HMPAO)–H] · ClO₄ (1) and its oxidized Schiff-base product [Ni(meso-HMPAO)-5H] · ClO₄ (2), where HMPAO is hexamethyl propylene amine oxime, are presented. Complex 2 results from the oxidation of 1 by molecular oxygen in basic aqueous solution. The structural change of the amine complex 1 to the Schiff-base complex 2 was investigated by the means of NMR spectroscopy and X-ray crystallography.