Aminopyrimidine-carboxyl(ate) interactions in trimethoprim maleate, an antifolate drug.
In the title cocrystal, trimethoprim maleate [2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidin-1-ium maleate], C(14)H(19)N(4)O(3)(+).C(4)H(3)O(4)(-), the trimethoprim molecule is protonated at N1. The carboxyl group of the maleate ion makes a specific double hydrogen bond of type N-H.O with the 2-amino group and the protonated N1 atom of the trimethoprim cation which is similar to the carboxylate-trimethoprim cation interaction observed in the complex of dihydrofolate reductase with trimethoprim. The pyrimidine moieties of trimethoprim cations are centrosymmetrically paired through a pair of N-H.N hydrogen bonds involving the 4-amino group and the pyridinium N3 atom of a symmetry-related molecule. One of the O atoms at the maleate carboxylate group bridges the 2-amino and 4-amino groups on either side of the paired trimethoprim cations. The other O atom of the carboxylate group forms an intramolecular O-H.O hydrogen bond with the carboxyl group. These characteristic hydrogen bonds result in infinite two-dimensional aggregation of rings into a supramolecular ladder, which is further crosslinked through weak C-H.O interactions with methoxy groups of neighbouring trimethoprim molecules to form a layered structure.
Prabakaran
P
P
Department of Chemistry, Bharathidasan University, Tiruchirapalli 620 024, India.
Robert
J J
JJ
Muthiah
P T
PT
Bocelli
G
G
Righi
L
L
D018360:Crystallography, X-Ray; D005493:Folic Acid Antagonists / Q000737:chemistry*; D008298:Maleates / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry*
C431784:2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidin-1-ium maleate; D005493:Folic Acid Antagonists; D008298:Maleates; D011743:Pyrimidines