Monika Wrona

Electrochemical properties of 4-thiouracil derivatives

A study has been made of the polarographic behaviour of 4-thiouracil and its N-methylated derivatives, and of 4-thiouridine. Similar electrochemical properties are exhibited by all the compounds with a 2-keto-4-thione structure. In acid medium they give a typical catalytic hydrogen discharge wave, which disappears completely at pH values above 6. At pH values above 4.2 a second catalytic wave appears. Maximal catalytic activity is exhibited at pH 7.1, and decreases with increasing pH. Both catalytic waves possess pronounced surface characteristics, most likely due to adsorption of the molecules with differing orientations on the electrode surface. The second catalytic wave overlaps the reduction wave, which is placed in evidence under conditions where the catalytic effect is absent. The reduction wave is a 4e−/4H+ process involving reduction of the 4-thiouracil ring to 5,6-dihydropyrimidone-2. The same product is formed by a 2e−/2H+ reduction of 5,6-dihydro-4-thiouracil. The potential applications of the electrochemical properties of 4-thiouracil to studies on tRNA structure are discussed.

Electrochemical reduction of 4-thiomethyluracil derivatives

Summary The polarographic reduction of 4-thiomethyluracil, 1-methyl-4-thiomethyluracil and 4-thiomethyluridine was investigated by d.c. and a.c. polarography, cyclic voltammetry at HMDE, preparative electrolysis, and coulometry. The reduction mechanisms of the compouds studied were found to be similar, i.e. a two-step reduction in the pH range 1.0–6.0, and merging of the two steps into one at higher pH. In the 1st two-electron reduction step HSCH3 was eliminated. Subsequently, in the 2nd one-electron reduction step, a free radical was formed, which underwent either dimerization to 6,6′-bis-(3,6-dihydropyrimidone-2) or a further one-electron reduction to 3,6-dihydropyrimidone-2. The products obtained were identical to those formed by polarographic reduction of pyrimidone-2 and cytosine. The compounds investigated and their reduction products were strongly absorbed on mercury.

Electrochemically induced pyrimidine dimerization

Abstract A study has been made of the polarographic behaviour and the mechanisms of electroreduction of N-methyl derivatives of pyrimidone-2 and 4-methylthiouracils. One of the major electroreduction products of all the foregoing is a 6,6′-bis(3,6-dihydro-pyrimidone-2) dimer similar to that previously described as the major reduction product of the parent pyrimidone-2. The properties of the dimers are described, including their ability to undergo photodissociation to the parent pyrimidone-2 derivatives. The mechanisms of the electroreductions and their significance in relation to the photochemistry of some nucleic acids and their constituents is discussed.

281 - Electroreduction mechanism of 2-thiopyrimidine derivatives: Part I. Polarographic study

The mechanism of the polarographic reduction of 2-thiopyrimidine and its N— and S—methyl derivatives, with stabilized tautomeric thione or thiol structure, has been studied over the normal pH range. 2-Thiol-pyrimidine undergoes electroreduction via the same pathway as 1.4.6-trimethyl-2-thiopyrimidine in the thione form. The C−4 atom is th electroactive center and the sulfur substituent remains intact. In a ie−, iH+ process a free radical is formed which dimerizes to products identified as 4,4′-bis-(3,4-dihydro-2-thiopyrimidine) and the corresponding C−4, C6− and/or N1-methyl derivatives. For 2-thiopyrimidine the free radical can be further reduced (ie− process) to 3,4-dihydro-2-thiopyrimidine. In the use of 4,6-dimethyl-2-thiomethylpyrimidine, a model compound of the thiol form, the electroactive center is shifted to the carbon C−2 and the sulphur substituent undergoes elimination.

Electrochemically Reduced Photoreversible Products of Pyrimidine and Purine Analogues

HI Electroroduction of 2-Oxopyrimidine . . . . . . . . . . . . . . . . . 140 III.1 Pyr imidone-2 . . . . . . . . . . . . . . . . . . . . . . . 140 I I I . l .1 Pho tochemis t ry o f Pyr imidone-2 D i m e r Reduc t ion Produc t 141 III. 1.2 Te t ramer ic P h o t o p r o d u c t o f Thymine and Pyr imidone-2 141 III .2 N M e t h y l a t e d Pyr imidone-2 . . . . . . . . . . . . . . . . . 143 III .3 4 ,6 -Dimethy lpyr imidone-2 . . . . . . . . . . . . . . . . . . 144 I I I .4 Pyr imidone-2 in D M S O . . . . . . . . . . . . . . . . . . . 146

Electrochemical reduction mechanism of 2-thiouracil derivatives

Summary The mechanism of the polarographic reduction of 2-thiouracil and its S-methyl and ethoxy derivatives with stabilized 2-thiol-4-keto or 2-thione-4-enol structure has been studied. 2-Thiouracil is not electroreducible in aqueous solutions. However, it exhibits a strong tendency to adsorption and association on the mercury electrode. 2-Thio-4-ethoxypyrimidine undergoes a 4 e − , 4 H + reduction which involves 2 e − reduction of the 3,4 N=C bond, elimination of the ethoxy substituent to form 2-thiopyrimidine and 2 e − , 2 H + reduction of the latter to 3,4-dihydroderivative. For 2-thiomethyluracil, a model compound of the 2-thiol-4-keto form, the electroactive centre is shifted to C-2 and in a 2 e − , 2 H + reduction process the sulphur substituent undergoes elimination, to give pyrimidone-4; the latter can be further reduced at more negative potentials to tetrahydroderivatives (4 e − -process). Biological implications of these results have been discussed.

Electroreduction mechanism of 2-thiopyrimidine derivatives: Part II. Correlation with electronic structure indices

Summary The experimentally observed changes in the electroreductionmechanism of 2-thiopyrimidine derivatives were interpretated on the basis of their electronic structure, calculated by the CNDO/2 and Huckel methods. For some of the examined compounds a linear correlation has been found between the experimental measurement of the electron acceptor properties of molecules (represented by a polarographic potential U 1/2 Red ) and the theoretical computation of the energy of the lowest unoccuppied molecular orbital (LUMO). For the same compounds it was also found that U 1/2 Red linearly correlates with the N 3 =C 4 bond order and the electronic charge distribution on N 3 and C 4 but not with other bond orders and charges. These results confirm the experimental data, indicating that the N 3 =C 4 bond is the electroactive centre of the molecules considered.

Investigation of the enzymatic, chemical and electrochemical oxidation of 4-thiouracil

Abstract The electrochemical oxidation of 4-thiouracil (4TU) at the pyrolytic graphite electrode has been compared to its enzymatic oxidation with the type VI peroxidase/H 2 O 2 system and to chemical oxidation with H 2 O 2 . The results obtained support the conclusion that the electrochemical and enzymatic reactions proceed, in a chemical sense, by identical mechanisms, whereas the chemical oxidation of 4TU with H 2 O 2 exhibits a different mechanism. These investigations also give insights into the mechanism of 4TU oxidation by other oxidizing agents.

Electrochemical oxidation of 4-thiouracil to bis(4-thiouracil)disulfide and chemical transformations of the disulfide

Abstract The electrochemical oxidation of 4-thiouracil (4TU) and 4-thiouridine (4TUr), which give one voltammetric peak at the pyrolytic graphite electrode (p.g.e.), has been investigated by linear sweep and cyclic voltammetry, macroscale electrolysis and product analysis. Oxidation of 4TU and 4TUr is an irreversible 1 e − , 1 H + process leading to formation of free radicals which rapidly dimerize to bis(4-thiouracil)disulfide (DIS) or its riboside analog (rDIS). These disulfides can be readily electrochemically reduced back to the parent compounds. They also undergo spontaneous transformations in aqueous solution to various products, including the corresponding derivatives of 4TU, uracil, sulfenic acid and thiosulfonate, depending on pH and the presence of oxygen. The possible biological meaning of the results reported is discussed.