A refinement of the crystal structure of cytidine

Abstract

The crystal structure of cytidine has been refined by least-squares calculations to a final R index of 5.6 %. Three-dimensional photographic data were used. The essential features of the original structure are confirmed, but the standard deviations in the bond lengths are reduced to about 0.006 A and in the bond angles to less than 0.5 °. The distances and angles in the cytosine part of the molecule are closely similar to those found in cytosine monohydrate. The two angles at each external bond to pyrimidine appear to differ significantly. The N-glycosidic linkage is found to be 1.497 A. The two bonds to the furanose ring oxygen atom differ in length by 0.03 A. The existence of an intramolecular C-H • • • O interaction at 3.23 /k is confirmed.The crystal structure of cytidine, CgH1305N3, was determined by one of us fifteen years ago from three electron density projections refined to R=0. 17-0.19 (Furberg, 1950). Paul±rig & Corey (1956), not con. sidering this structure analysis reasonably reliable, deduced bond lengths and angles in the cytosine part of cytidine by considering the crystal structures of a number of other pyrimidines, mainly heavy atom derivatives. This work was later extended by Spencer Kinoshita, 1963), and precise information on the ribose residue has been obtained through three-dimensional analysis of calcium thymidylate (Trueblood, Horn & Luzzati, 1961) and adenosine 5-phosphate (Kraut & Jensen, 1963). However, cytidine is still the only unsubstituted nucleoside the structure of which has been solved. It contains no heavy atoms and its aromatic ring is not protonated. We have therefore refined the structure in order to obtain more exact information on this part of the nucleic acids. ExperimentalThe unit-cell dimensions were redetermined by leastsquares calculations based on measurements of 28 lines registered on a Guinier camcra calibrated against KC1. The following values were found" a--13.991 ± 0.002, b = 14.786 _ 0.002, c=5-116 i0.001 _~.The uncertainties indicated are estimated standard deviations. The space group is P212121 and there are four molecules in the unit cell. Integrated equi-inclination Weissenberg photographs hkO-hk2, hOl-h81 and Okl were taken. Of the total of about 1450 unique reflexions within the Cu Ka limit, 1195 were recorded. Of these 165 were too weak to measure. The intensities of each of the four equivalent reflexions were measured on a Hilger photometer and the mean value taken. The weakest reflexions were estimated visually. Crystals with cross-sections approximately 0.1 × 0-1 mm were used and no correction for absorption was applied. The various levels were placed on an approximately common absolute scale by means of calculated structure factors based on the two-dimensionally refined structure. Refinement of the structureThe coordinates of the original structure were first refined by a number of difference syntheses in the a and c projections, including finally the thirteen hydrogen atoms. A common isotropic temperature factor was applied, and the values 0.12 a...

Distance Measurements in Multiply Labeled Crystalline Cytidines by Dipolar Recoupling Solid State NMR

“…21 In nucleic acids, the isotropic chemical shifts of the sugar ring resonances are indicative of the ring conformation, 29 and the relatively upfield shifts of the C3′ and C5′ resonances in the cytidine spectra indicate that the sugar ring is in the C3′ endo conformation characteristic of A-form nucleic acid structures. This also agrees with the ring conformation observed in the crystal structure.…”

“…This also agrees with the ring conformation observed in the crystal structure. 21 The C2 carbon (138.9 ppm) may be indentified by a strong cross-peak to C1′ (88.8 ppm). Additionally, a very weak positive connectivity between the aromatic C2 nucleus and C2′ on the ribose ring appears with two repetitions of DRAWS mixing.…”

“…Input parameters for the simulations were determined as follows: CSA tensor principal values were measured using the method of Herzfeld and Berger 25 applied to a series of CP-MAS spectra of crystalline cytidine acquired at different sample spin rates. Internuclear distances were determined from the crystal structure of Furberg et al 21 The orientation of the cytidine C2 CSA tensor in the molecular frame was assumed to be analogous to that of the C2 tensor in 2′-deoxythymidine. 26 For the labeled sugar ring carbons, the CSA tensor orientations were assumed to be the same as those determined by McDowell et al for the analogous resonances in dipotassium R-D-glucose 1-phosphate dihydrate.…”

The crystal and molecular structure of 5,6-dihydroisocytidine monohydrate, C9H15N3O5.H2O

“…The presence of the saturated C(5)-C(6) bond is of a great influence on nucleobase geometry. For that reason the structure of cytidine (Furberg, Petersen & Romming, 1965) cannot be compared with 5,6-dihydroisocytidine. The ribose moiety is in the C(3')-endo conformation in both compounds and therefore its geometry is comparable to those given by Sundaralingam & Jensen (1965).…”

Pyridazine nucleosides. The structure and conformational analysis of 5-hydroxy-2-(1-β-D-ribofuranosyl)-3(2H)-pyridazinone

“…Lists of all bond lengths and angles within the nucleoside are compiled in Tables 2 and 3, respectively. A comparison of bond lengths within the pyrimidine portion of uridine (Green, Rosenstein, Shiono, Abraham, Trus & Marsh, 1975), cytidine (Furberg, Petersen & Romming, 1965), thymidine (Young, Tollin & Wilson, 1969), and their 3-deaza (Schwalbe & Saenger, 1973a;Hutcheon & James, 1977) and 6-aza derivatives (Schwalbe & Saenger, 1973b;Singh & Hodgson, 1974b;Banerjee & Saenger, 1978) reveals that a primary feature of the 6-aza structures is the expected shortening of the C(5)-N(6) bond and concomitant lengthening of the C(4)-C(5) bond relative to the corresponding bonds in the natural nucleosides. Another interesting characteristic is that the N(6)-N(1) bond length is very similar to the C(6)-N(1) distance in the natural analogs, indicating a loss of some double-bond character in the aza analogs.…”