Molecular dimensions and properties of N-[1-(2-hydroxyethyl)-2-nitro-1H-imidazol-1-yl]acetamide (SR2508).
Hypoxic cells in tumors are resistant to radiation and chemotherapy treatment. To decrease this resistance, 2-nitroimidazoles are used as radiation and chemical sensitizers in the treatment of tumors. Their use is marred by their toxicity. Therefore, the compound SR2508, a new 2-nitroimidazole derivative, was introduced in an attempt to obtain a less toxic nitroimidazole than those used thus far. The molecular structure and conformation of SR2508, determined from X-ray diffraction studies, is reported. The compound, formula C7H10N4O4, molecular weight 214.18, crystallizes in the monoclinic system, space group P2(1)/c, unit cell dimensions a = 12.052(3), b = 11.116(4), c = 7.330(2) A, beta = 106.94(2) degrees, V = 939.4(5) A3, Z = 4. The crystal structure was refined to Robs = 0.041. The imidazole and C-NO2 groups are each planar and inclined at 6.6 degrees to each other. The side chain, which contains an amide group, is also planar. There are hydrogen bonds between different molecules and they involve O(11) and O(15), as well as N(12) and O(15). When compared to other 2-nitroimidazoles that have been clinically tested, the hydrogen bonds in SR2508 account for the increased hydrophilic character of the compound. Based on the crystal structure data, models for a possible interaction between SR2508 and DNA have been proposed.
Dabrow
M B
MB
University of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, Stratford 08084.
Katz
H
H
O'Dwyer
P J
PJ
Afshar
C
C
Glusker
J P
JP
D003460:Crystallization; D017341:Etanidazole / Q000737:chemistry*; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D015394:Molecular Structure; D014961:X-Ray Diffraction
D017341:Etanidazole