Crystal engineering of cytidine and deoxycytidine sulphates. I. Preparation, and unusual properties.

Abstract

From three possible simple salts of Cyd (dCyd) 1 with H 2SO 4, we succeeded in preparation of only one type of a crystalline salt in which two monoprotonated cations: 2CydH + (2dCydH +) pair with one sulphate dianion (SO 2− 4) (Fig.3) 4. Attempts to obtain crystalline sulphates with dimeric hemi-cations and/or hydrogen sulphate anions completely failed. The presence or absence of 2′OH group drastically changes the thermochemical properties of Cyd and dCyd sulphates (Fig.4). Cyd sulphate undergoes rapid one-step thermal decomposition within the range 205–260°C with subsequent smoth further mass loss up to 340°C, whereas dCyd sulphate (Form A and B) undergoes a three stage thermal decomposition: I. 25–170°C, II. 170–230°C, III. 230–340°C. Clear differences in the DSC and TGA curves of both types of salt may reflect dissimilar mechanisms of their crystal structure decomposition. An extremely easy transformation of dCyd sulphates into the hydrochloride salt in the crystal phase was discovered. The reaction proceeds both in finely ground stoichiometric mixtures of 2dCydH +·SO 2− 4 + 2NaCl or KCl, and also in a nujol suspension of pure dCyd sulphate placed between NaCl plates. Similar transformation occurs also with KBr and leads to the crystalline dCyd hydrobromide which is isostructural to dCyd hydrochloride. Form A of dCyd sulphate, which contains methanol trapped in its crystal lattice, is particularly susceptible to the above transformation. Cyd sulphate undergoes transformation to hydrochloride and hydrobromide salts by a few orders of magnitude slower. These unidirectional ion exchange reactions proceed quantitatively in crystalline phase only, showing the significance of crystal structures of nucleosides and their salts. Unusual properties of sulphate counter anions may be exploited for a controlled modulation of reactivity of nucleosides. The unidirectional ion exchange reactions take place in 100 % in crystalline phase only , revealing the significance of information coded in crystal structures of nucleosides.