Amino-substituted O-6-benzyl-5-nitrosopyrimidines: interplay of molecular, molecular-electronic and supramolecular structures

A Quesada, A Marchal, M Melguizo, M Nogueras, A Sanchez, J N Low, D Cannon, D M M Farrell, C Glidewell

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

The structures of eight 2,4,6-trisubstituted-5-nitrosopyrimidines (one of which crystallizes in two polymorphs) have been determined, including seven O-6-benzyl derivatives which are potential, or proven, in vitro inhibitors of the human DNA-repair protein O-6-alkylguanine-DNA-transferase. In the derivatives having an amino substituent at the 4-position, an intramolecular N-H...O hydrogen bond with the nitroso O as an acceptor leads to an overall molecular shape similar to that of substituted purines. There is a marked propensity for these nitroso compounds to crystallize with Z' = 2. The structure of an analogue with no nitroso group is also reported for comparative purposes. Compounds containing the N-alkyl substituents DNHCH2COOEt, -NHCH2CH2COOEt and -NHCH(CH2Ph)COOEt, derived from amino acid esters, exhibit a rich variety of conformational behaviour, and in all of the nitroso compounds the bond lengths provide strong evidence for a highly polarized electronic structure. Associated with this polarization is extensive charge-assisted hydrogen bonding between the molecules, leading to supramolecular aggregation in the form of finite (zero-dimensional) aggregates, chains, molecular ladders, sheets and frameworks.

Original languageEnglish
Pages (from-to)300-315
Number of pages16
JournalActa Crystallographica. Section B, Structural Science
Volume58
DOIs
Publication statusPublished - Apr 2002

Keywords

  • HUMAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE
  • DIFFRACTION DATA
  • O-6-BENZYLGUANINE
  • DERIVATIVES

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