Instability of 2,2-di(pyridin-2-yl)acetic acid. Tautomerization versus decarboxylation

The DFT calculations at the B3LYP level with 6-311G** basis set were carried out in order to reveal whether tautomerization or decarboxylation is responsible for the instability of 2,2-di(pyridin-2-yl)acetic (DPA) and 1,8-diazafluorene-9-carboxylic (DAF) acids. The carboxyl protons in both compounds are involved in the intramolecular hydrogen bonds (the pyridine nitrogen atoms are the hydrogen bond acceptors). Although formation of two intramolecular OH···N hydrogen bonds in the enols of both carboxylic acids enables effective electron delocalization within the quasi rings (···HO − C = C − C = N), only ene-1,1-diol of DAF has somewhat lower energy than DAF itself (ΔE is ca. 7 kcal mol^-1). DPA and its enediol have comparable energies. Migration of the methine proton toward the carbonyl oxygen atom (to form enediols) requires overstepping the energy barriers of 55-57 kcal mol^-1 for both DPA and DAF. The enaminone tautomers of the acids, formed by migration of this proton toward the pyridine nitrogen atom, are thermodynamically somewhat more stable than the respective enediols. The energy barriers of these processes are equal to ca. 44 and 62 kcal mol^-1 for DPA and DAF, respectively. Thus, such tautomerization of the acids is not likely to proceed. On the other hand, the distinct energetic effects (ca. 15 kcal mol^-1) favor decarboxylation. This process involves formation of (E)-2-(pyridin-2(1H)-ylidenemethyl)pyridine and its cyclic analogue followed by their tautomerization to (dipyridin-2-yl)methane and 1,8-diazafluorene, respectively. Although the later compound was found to be somewhat thermodynamically more stable, kinetic control of tautomerization of the former is more distinct.     

Circadian variations of plasma renin activity (PRA), aldosterone and electrolyte concentrations in plasma in pregnant and non-pregnant goats

The aim of this study was to estimate and analyse circadian variations of the renin-angiotensin-aldosterone system (RAA) activity in blood of goats and the influence of late pregnancy on the circadian variations of RAA system. The study was carried out on a group of 17 non-pregnant and 9 pregnant goats. The animals were kept in uniform environmental conditions, (9 h light/15 h darkness). Blood samples were collected seven times over a period of 24 h, every 4 h. Plasma renin activity (PRA), plasma aldosterone (PA), sodium, potassium and chloride concentrations were determined. PRA and PA of both groups changed during 24 h, with the highest values in the dark phase and with higher RAA system activity (especially during the night) in the pregnant goats. In the non-pregnant goats, no circadian changes in PRA and PA were observed. The circadian changes in PRA and PA found in pregnant goats had acrophases at 06:27 h and 01:13 h, respectively. Plasma electrolyte concentrations in both groups of goats also changed during 24 h. These results suggest that circadian changes of potassium concentration in plasma of goats during late pregnancy may be one of the main factors affecting the RAA system.     

The purine metabolism of human erythrocytes

This review summarizes currently available information about a crucial part of erythrocyte metabolism, that is, purine nucleotide conversions and their relationships with other conversion pathways. We describe the cellular resynthesis, interconversion, and degradation of purine compounds, and also the regulatory mechanisms in the conversion pathways. We also mention purine metabolism disorders and their clinical consequences. The literature is fragmentary because studies have concentrated only on selected aspects of purine metabolism; hence the need for a synthetic approach. Published in Russian in Biokhimiya, 2006, Vol. 71, No. 5, pp. 581–591.