5-Ethynyl-2'-deoxycytidine: a DNA building block with a 'clickable' side chain

Area of Science:

• Crystallography
• Structural Chemistry
• Nucleoside Analogues

Background:

• Understanding the solid-state structure of nucleoside analogues is crucial for drug design.
• Conformational flexibility can impact the biological activity and physical properties of molecules.

Purpose of the Study:

• To elucidate the crystal structure and conformational properties of 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-ethynylpyrimidin-2(1H)-one.
• To analyze the N-glycosylic bond and sugar pucker conformations in the crystalline state.

Main Methods:

• Single-crystal X-ray diffraction analysis was employed to determine the molecular structure.
• Conformational parameters, including N-glycosylic bond angles (χ) and sugar pucker (P, τ(m)), were calculated.

Main Results:

• Two distinct conformers (I-1 and I-2) were identified in the crystalline state.
• Both conformers exhibit an anti-range N-glycosylic bond conformation (χ ≈ -150°).
• Conformer (I-1) shows a C2'-endo sugar pucker, while conformer (I-2) displays a C3'-exo sugar pucker. The ethynyl groups are positioned proximally and do not engage in hydrogen bonding.

Conclusions:

• The compound exhibits significant conformational diversity in the solid state, with distinct sugar puckerings.
• The observed layered 3D crystal structure arises from the arrangement of these conformers.
• The ethynyl group's role in crystal packing appears to be non-covalent and positional.