M.D. Bratek-Wiewiórowska

Crystal Structure of 2′-Deoxycytidine Hemidihydrogenphosphate Reveals C+·C Base Pairs and Tight, Hydrogen-Bonded (H2PO4 −)∞ Columns (1)

Abstract 2′-Deoxycytidine hemidihydrogenphosphate has been crystallized in the hexagonal space group P62 with α=25.839(3), c = 12.529(1) A. The structure has been solved using the Patterson search method. The asymmetric unit contains two protonated, base-paired 2′-deoxycytidine dimers and two H2PO4 − anions. The C+·C base pairs are composed of a protonated and a neutral species each and are triple H-bonded, the central N(3)…N(3) bonds being 2.850(7) and 2.884(5) A. The conformations of the four nucleosides fall in the same category (sugar puckers 2·-endo, glycosidic links anti) but in one of them the glycosidic torsion angle is quite low with consequences in other geometrical parameters. The H2PO4 − anions are located on twofold axes and form two types of tight columns with P…P separations about 4.18 A The neighboring units along a column are linked via two very short O…H…O hydrogen bonds (O…O about 2.49 A) leading to effective equalization of the P-O bonds. The base pairs of the two dC+·dC cations are co...

The nature of drastic differences in the recognition of protonated cytidinium and deoxycytidinium cations by their parent nucleosides within dihydrogenphosphate salts in the light of the computer-simulated crystal structure of dCyd hemiphosphate (dCyd)2H+ H2PO−*4

Abstract In the crystal structures of cytidine (Cyd), deoxycytidine (dCyd) and their dihydrogen phosphates, we have found important information about their abilities to resist transformation in the solid phase. On this basis we predicted and realised the transformation of the monophosphate into the hemiphosphate of dCyd and vice versa [dCydH + H 2 PO − 4 ⇌ (dCyd) 2 H + H 2 PO − 4 ], and simulated the latter structure by computer modelling of the former. We also discuss the molecular mechanism of both transformations in which protonation and deprotonation processes play leading roles. In the light of observations accumulated in this paper, further progress in the crystal engineering of nucleosides appears to be promising.

Further investigation of the chemistry and structure of angustifoline and its derivatives: Part V. The conformation of angustifoline and its simple derivatives

Abstract Most of the structural assignments presented in this paper were based on the conformation of angustifoline selectively deuterated at the 13β position (13β 2 H I). To confirm the absolute stereoselectivity of the reaction introducing 2 H at 13C on the β face, 13β 2 H I was transformed into four deuterated derivatives of I and sparteine, the structures of which have previously been determined (in two cases by X-ray analysis). Angustifoline (I), dihydroangustifoline (II) and deoxyangustifoline (V) exist exclusively in the all-chair conformation, in which the 12NH bond and allylic chain are axial, and the lone pair of 12N equatorial. The unusual orientation of the NH bond in the piperidine fragment is stabilized in V by an intramolecular hydrogen bond, but there is no clear evidence as to which factors stabilize this conformation in I and II. The NH protons in I and II are inaccessible to self-association and hence their spectroscopic properties (IR, 1 H NMR) differ considerably from those of “normal” piperidine derivatives. N -methyl- and N -cyanomethyl-angustifoline (III and IV) exist predominantly in the all-chair conformation, with the N -methyl (or N -cyanomethyl) substituent equatorial, and the lone pair at 12N axial. The infrared evidence is in full agreement with the X-ray data for a single crystal of IV. Drastic differences between the conformation of III and IV and that of lupanine (VIII) make it possible to discuss the factor responsible for the conformation of the flexible cis quinolizidine moiety in the molecule of sparteine and its derivatives. Tetrahydrorombifoline (VI) and its 11-cyano derivative (VII), like III and IV, exist in the all-chair cisoidal conformation. The absolute stereoselective exchange of hydrogen atoms by deuterium at 11β, 13β and bis-14 positions makes it possible to establish the contribution of specific ν(CH) app and ν(C 2 H) app bands to the shape and intensity of the “ trans ” band. A semi-quantitative measurement of the relative intensities of ν(C 2 H) bands at ∼2200 and ∼2000 cm −1 in deuterated III and IV gave promising results which could be used for the determination of the conformational equilibria.

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

Abstract From three possible simple salts of Cyd (dCyd)1 with H2SO4, we succeeded in preparation of only one type of a crystalline salt in which two monoprotonated cations: 2CydH+ (2dCydH+) pair with one sulphate dianion (SO2−4) (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+·SO2−4 + 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.

Multiforms and behavior of crystalline 2′-deoxycytidine

Abstract Three different forms of 2′deoxycytidine (dCyd) could be obtained by crystallization from different mixtures of solvents. In the solid state, under suitable conditions, five forms of dCyd could be obtained: dCydA, dCydB, dCydC·H2O, dCydC-anhydro and dCydD. The conditions of transformation in the solid state of one form of dCyd into another were precisely determined and a comparative analysis of all the forms has been carried out. The course of transformations was followed by FTIR-PAS spectroscopy.

Comparative study of the hydration systems formed during interactions of hydrogen phosphate dianions with putrescine, nor-putrescine and magnesium dications

Abstract A comparative study of hydration systems, formed as a result of the interaction between hydrogen phosphate dianions and three naturally occurring cations (putrescine (Put), its nor-homologue (nPut) and magnesium), is presented. On the basis of X-ray data and IR, NMR and calorimetric measurements, we have determined how the structure and physicochemical properties of the cations influence the system of phosphate residue hydration. Our study demonstrates that the stability of the hydration systems depends not only on the character of the bonds used by water to link with other salt components (coordinate or hydrogen bonds), but also on the location of the water molecules in the crystal lattice. In addition, contrary to magnesium salts, the dehydration of diamine (Put and nPut) hydrogen phosphates is reversible. Both dehydration and rehydration processes take place in the solid state. During rehydration, the crystalline anhydrous salt absorbs water molecules from the atmosphere. This leads to the reconstruction of the hydrated salt structure; this means that the salt which is the product of rehydration is identical with that obtained by crystallization from water solution.

Further investigations on the chemistry and structure of angustifoline and its derivatives. Part 6. New evidence of factors responsible for basicity of α-cyanoamines: crystal and molecular structure of N-cyanomethylangustifoline

The crystal and molecular structure of N-cyanomethylangustifoline (III) has been determined from three-dimensional X-ray data by direct methods and refined by full-matrix least-squares calculations to a final R of 0.039 for 1 055 observed reflections. Crystals are monoclinic, a= 10.223(1), b= 9.416(1), c= 7.846 4(7)A, β= 94.741(8)°, space group P21, and Z= 2.The conformation of the cyanomethyl group was found to be the same as that preferred in solution. The lone pair at nitrogen N(12), bearing the cyanomethyl group, is trans to the nitrile group and gauche to the methylene hydrogen atoms. Possible factors stabilizing this conformation are discussed. Direct electrostatic interactions through space between the lone pair and ‘acidic’ protons of the bridging methylene group may cause a greater decrease in the basicity of α-cyanoamines than that due to the inductive effect of the nitrile group.There is a weak C–H ⋯ OC intermolecular hydrogen bond [3.284(5)A].

Cytidinium H-Phosphonate Monohydrate, bis 2′-Deoxycytidinium H-Phosphonate and 2′-Deoxycytromium H-Phosphonate -Structures and Properties

Abstract The crystal structures of cytidinium H-phosphonate monohydrate, bis 2′-deoxycytidinium H-phosphonate and 2′-deoxycytidinium H-phosphonate have been determined by single crystal X-ray diffraction and FTIR spectroscopy. The influence of protonation and hydrogen bond formation on geometry of the cytidine fragment has been studied. All three compounds have similar geometry and conformation but they form different H-bond networks. Contrary to the phosphates of cytidine and deoxycytidine, the phosphonates do not form direct base pairs but they strongly interacts with H3PO3 acid and/or its anions present in the crystal lattice. This seems to be more favourable than the base-base interactions. As a result a pleated sheets are formed consisting from alternating columns of the cations and anions. The sheets are joined by additional O-H… O=P bonds giving a 3D network.

Monomorphism of cytidine (Cyd) vs. polymorphism of 2′deoxycytidine (dCyd). Structural and functional consequences

Abstract It has been found that 2′deoxycytidine (dCyd) crystallizes in different forms, denoted dCyd A, dCyd B and dCyd C·H2O. In the crystal lattice of the newly discovered form dCydC·H2O there is a crystalline water molecule present. The monohydrate of dCydC, under suitable conditions (RT, over P2O5, 48h), undergoes transformation into the fully dehydrated form—dCydC anhydro. The whole process of de- and re-hydratation has been observed by FTIR-PAS spectroscopy. The nature of the differences and similarities between structural and functional properties of crystalline forms of 2′dCyd and Cyd molecules has been discussed.