Amino-substituted O⁶-benzyl-5-nitrosopyrimidines: interplay of molecular, molecular-electronic and supramolecular structures

Abstract

The structures of eight 2,4,6-trisubstituted-5-nitrosopyrimidines (one of which crystallizes in two polymorphs) have been determined, including seven O6-benzyl derivatives which are potential, or proven, in vitro inhibitors of the human DNA-repair protein O6-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 —NHCH2COOEt, —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.

Adsorption of Zn2+ and Cd2+ from Aqueous Solution onto a Carbon Sorbent Containing a Pyrimidine–Polyamine Conjugate as Ion Receptor

“…This trend to the inverse orientation of the pyrimidine planes in the stacking of analogous pyrimidine compounds has been widely observed. [17] Adsorption of Zn 2+ and Cd…”

Supramolecular structures of N 4-substituted 2,4-diamino-6-benzyloxy-5-nitrosopyrimidines

“…We have recently found that in a number of 2-amino-6benzyloxy-5-nitrosopyrimidines the supramolecular aggregation involves not only conventional hydrogen bonds of NÐ HÁ Á ÁN and NÐHÁ Á ÁO types, but also those of the NÐ HÁ Á Á%(arene) type, where the arene group involved is that of the O 6 -benzyl unit (Quesada, Low et al, 2002;Quesada, Marchal et al, 2002). Since NÐHÁ Á Á%(arene) hydrogen bonds do not occur in all of the 2-amino-6-benzyloxy-5-nitrosopyrimidines which we have studied, we have now undertaken a systematic study of a range of such compounds, carrying a range of amine substituents at the 4-position, in an attempt to discern the conditions under which such interactions are observed.…”

“…Since NÐHÁ Á Á%(arene) hydrogen bonds do not occur in all of the 2-amino-6-benzyloxy-5-nitrosopyrimidines which we have studied, we have now undertaken a systematic study of a range of such compounds, carrying a range of amine substituents at the 4-position, in an attempt to discern the conditions under which such interactions are observed. To this end, we present here a study of the molecular and supramolecular structures of (1)±(9) [see Scheme (I)]; of these, (6) has already been discussed elsewhere (Quesada, Marchal et al, 2002) and we refer to it here simply for the purposes of comparison. The amine substituents at the 4-position encompass a relatively wide range of structural diversity, including primary amines bearing linear alkyl substituents [of short, (1), medium, (2) and 7, and large chain length, (3)], cyclohexyl compound (4), phenyl compound (5), and benzyl compound (6), as well as piperidino substituents in (8) and (9) as representative of secondary amines.…”

Redetermination of 6-amino-5-formyl-1,3-dimethyluracil monohydrate at 120 K: a polarized molecular structure and two interwoven hydrogen-bonded frameworks

“…Recent studies (Low et al, 2000;Quesada et al, 2002;Melguizo et al, 2003) of amino-substituted 5-nitrosopyrimidines have provided compelling evidence for the development of extensively polarized molecular±electronic structures, in which forms such as A (Low et al, 2000) and B (Quesada et al, 2002;Melguizo et al, 2003) (see scheme) make important contributions to the overall molecular±electronic structures, normally represented by forms such as C and D. These polarized structures in turn lead to the formation of supramolecular networks built from charge-assisted (Gilli et al, 1993) hydrogen bonds. With these recent ®ndings in mind, we have now reinvestigated the structure of the title compound, (I) (Fig.…”

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The title compound [systematic name: 6-amino-5-formyl-1,3dimethylpyrimidine-2,4(1H,3H)-dione monohydrate], C 7 H 9 -N 3 O 3 ÁH 2 O, has been reexamined at 120 K. The improved precision of the intramolecular dimensions provides evidence for a polarized molecular±electronic structure, and the molecular components are linked by one NÐHÁ Á ÁO and two OÐ HÁ Á ÁO hydrogen bonds into two interwoven three-dimensional frameworks, which are weakly linked by the longer component of a three-centre NÐHÁ Á Á(O) 2 hydrogen bond.

CommentRecent studies (Low et al, 2000;Quesada et al, 2002;Melguizo et al, 2003) of amino-substituted 5-nitrosopyrimidines have provided compelling evidence for the development of extensively polarized molecular±electronic structures, in which forms such as A (Low et al, 2000) and B (Quesada et al, 2002;Melguizo et al, 2003) (see scheme) make important contributions to the overall molecular±electronic structures, normally represented by forms such as C and D. These polarized structures in turn lead to the formation of supramolecular networks built from charge-assisted (Gilli et al, 1993) hydrogen bonds. With these recent ®ndings in mind, we have now reinvestigated the structure of the title compound, (I) (Fig.

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