Amino-substituted O(6)-benzyl-5-nitrosopyrimidines: interplay of molecular, molecular-electronic and supramolecular structures.
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 -NHCH(2)COOEt, -NHCH(2)CH(2)COOEt and -NHCH(CH(2)Ph)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.
Quesada
Antonio
A
Departamento de Química Inorgánica y Orgánica, Universidad de Jaén, 23071 Jaén, Spain.
Marchal
Antonio
A
Melguizo
Manuel
M
Nogueras
Manuel
M
Sánchez
Adolfo
A
Low
John N
JN
Cannon
Debbie
D
Farrell
Dorcas M M
DM
Glidewell
Christopher
C