The Relationship between Hydrogen Bonding and Base Stacking in Crystalline 4‐Thiouridine Derivatives

Abstract

The tRNA minor constituent 4-thiouridine and four of its derivatives with identical or similar nucleobases (arabino-4-thiouridine, 1-methyl-4-thiouracil, 3′-O-acetyl-4-thiothymidine and 2,4-dithiouridine) have been crystallized from water and examined by single-crystal X-ray diffraction methods. From the packing patterns and hydrogen-bonding schemes found in the crystal structures the following observations were made. 1 The forces which determine the crystal structures are mainly stacking interactions due to hydrophobic and polarization forces. The hydrogen-bonding forces play only a minor or no role. 2 The hydrogen-bond formation is determined by geometrical factors imposed on the system through packing patterns. 3 Oxygen atoms, due to their greater electronegativity, are better proton acceptors than sulfur atoms. However, when certain stacking patterns must be followed, all predictions concerning hydrogen-bonding schemes become meaningless. 4 In cocrystals of complementary base pairs, however, the hydrogen bonding schemes are determining the crystal structures.