Graham E. Jeffs

Photocatalytic degradation of 1,4-dioxane in aqueous solution

Abstract 1,4-Dioxane is readily mineralized by the photocatalytic action of TiO 2 via an accumulation and slower degradation of ethylene diformate.

Guanine sulphinate is a major stable product of photochemical oxidation of DNA 6-thioguanine by UVA irradiation

The DNA of patients taking the immunosuppressant and anticancer drugs azathioprine or 6-mercaptopurine contains 6-thioguanine (6-TG). The skin of these patients is selectively sensitive to ultraviolet A radiation (UVA) and they suffer an extremely high incidence of sunlight-induced skin cancer with long-term treatment. DNA 6-TG interacts with UVA to generate reactive oxygen species, which oxidize 6-TG to guanine sulphonate (GSO3). We suggested that GSO3 is formed via the reactive electrophilic intermediates, guanine sulphenate (GSO) and guanine sulphinate (GSO2). Here, GSO2 is identified as a significant and stable UVA photoproduct of free 6-TG, its 2′-deoxyribonucleoside, and DNA 6-TG. Mild chemical oxidation converts 6-TG into GSO2, which can be further oxidized to GSO3—a stable product that resists further reaction. In contrast, GSO2 is converted back to 6-TG under mild conditions. This suggests that cellular antioxidant defences might counteract the UVA-mediated photooxidation of DNA 6-TG at this intermediate step and ameliorate its biological effects. In agreement with this possibility, the antioxidant ascorbate protected DNA 6-TG against UVA oxidation and prevented the formation of GSO3.

Photo-induced electron transfer in small peptides: glycylalanine

Participation of the peptide bond in photoinduced electron transfer accounts for product distributions in the photolysis of XG dipeptides and predicts the possibility that the side-chain will be involved in similar reactions of GX dipeptides. Product analysis following exposure of aqueous glycyl-DL-alanine to UV radiation shows this prediction is fulfilled. Thus, unlike XG peptides, glycylalanine degrades to acetamide substantially without co-production of CO2 and to products where bonding in the side-chain is involved in relaxation of the intermediate diradical. At a lower pH, decarboxylation radicals from glycylalanine have the opportunity to disproportionate as well as dimerize, and this accounts satisfactorily for the difference in product distribution when compared with that from XG photolysis under the same conditions.

Enantioselection in peptide bond formation

Selectivity in abiotic condensations of amino acids remains controversial and stereochemically little explored. We find that competitive activated couplings of N-acyl derivatives of glycine, alanine, valine, proline and phenylalanine with binary, ternary and quaternary mixtures of amides and esters of the same group of amino acids show little selectivity among the reactants, except with respect to configuration, where a consistent and significant preference for heterochiral outcomes, mostly > 80%, is observed. One possible explanation of this selectivity predicts a predisposition to homochiral coupling under conditions that would require the two carboxyl functions to be co-facial in the activated complex.

Photochemically induced ring-opening in prolyl peptides

Abstract Irradiation of prolylglycine in neutral, aqueous solution results in decarboxylative ring-opening to 5-amino-N-hydroxymethylpentanamide.

Photoinduced electron transfer in aliphatic peptides

Product analysis in the photolysis of triglycine in neutral aqueous solution suggests that the initial intramolecular electron transfer from the carboxylate to the peptide group, shown to lead to efficient (ϕ 0.44 ± 0.11) photodegradation for glycylglycine, may be followed by transfer to the second peptide group.

Photodegradation of aryl sulfonamides: N-tosylglycine

Continuing uncertainty about pathways and consequences of the photolability of aryl sulfonamides is partly resolved by the results of comprehensive product analysis in the photolysis of aqueous N-tosylglycine, which indicate that intramolecular electron or hydrogen transfer (according to conditions) promote the widely reported S–N cleavage and reveal the nature of subsequent and competing processes.

Efficient one-step synthesis of diastereoisomeric cyclic dipeptides from amino acids: three diastereoisomers of cyclo-L-isoleucyl-L-isoleucine

Cyclic dipeptides formed by the self-condensation of amino acids in ethane-1,2-diol comprise readily separable diastereoisomeric mixtures which, in the case of isoleucine, affords three isomers in good yield.

Stereochemical preference for heterochiral coupling controls selectivity in competitive peptide synthesis

Competitive activated couplings of N-phthaloyl amino acids with amino acid dimethylamides show little selectivity among substrates in respect of their sidechains, but a consistent and significant preference for heterochiral outcomes.

Enhanced photodeamination of prolyl tripeptides

When compared with results from other tripeptides, high yields of ammonia in the aqueous photolyses of glycylprolylglycine and alanylprolylglycine suggest that the prolyl residue can promote peptide conformations favourable for long-range electron transfer.