The crystal structure of substituted purine derivative, 8-(3-butyl-4-phenyl-2,3-dihydrothiazol-2-ylidene)hydrazino-3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-diones, caffeine derivative, has been determined. It crystallized in monoclinic system and space group P21/c with unit cell parameters a = 15.2634 (9), b = 13.4692 (9), c = 11.9761 (7)？？, and β = 108.825 (3)°. Although each constituting moiety of the structure individually is planar, nonplanar configuration for the whole molecule was noticed. Molecular mechanics computations indicated the same nonplanar feature of the whole molecule. A network of intermolecular hydrogen bonds contacts and π interactions stabilized the structure. 1. Introduction Caffeine (1,3,7-trimethylxanthine or 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione) is a well-known purine derivative and can be biosynthesized naturally in plants from the purine nucleotides. Caffeine has wide range of pharmacological applications due to its effects on the central nervous, heart, and vascular system [1, 2]. Purine ring system is one of the most heterocyclic ring systems in nature possessing the potential to impact several areas, such as a better understanding of the biological effect of DNA damaging agents, enzymes/substrate interactions, and the development of more potent medicines, such as antineoplastic (anti abnormal tissue growth, tumor), antileukemic (blood cancer), anti-HIV (anti-human immunodeficiency virus), and antimicrobial. Moreover, caffeine has been found to enhance anticancer activity of some chemotherapeutic agents and ionizing radiation. Previously, it was reported that methylxanthines may protect cells against the cytotoxic (poisonous to cells) effects and significantly decrease the mutagenicity of the anticancer aromatic drugs [2]. Recently, the activity of the present compound has been studied and it was found to have a great pharmaceutical and pharmacological interest [2]. Neither the crystal structure nor the molecular modeling has been reported yet. Therefore, in the present work, we introduce the X-ray crystallographic analysis of the molecular structure and discuss the results with the molecular mechanics computations; such results should be valuable information in the fields of pharmaceutics and pharmacology. In computational terms, molecular mechanics is the least expensive and fastest method. It is a method to calculate the structure and energy of molecules for providing excellent structural parameters in terms of bond distances, angles, and so forth, for the most stable conformation of the molecules [3, 4].
References
[1]
H. Ashihara, A. M. Monteiro, F. M. Gillies, and A. Crozier, “Biosynthesis of caffeine in leaves of coffee,” Plant Physiology, vol. 111, no. 3, pp. 747–753, 1996.
[2]
S. M. Rida, F. A. Ashour, S. A. M. El-Hawash, M. M. El-Semary, and M. H. Badr, “Synthesis of some novel substituted purine derivatives as potential anticancer, anti-HIV-1 and antimicrobial agents,” Archiv der Pharmazie, vol. 340, no. 4, pp. 185–194, 2007.
[3]
A. Leach, Molecular Modelling: Principles and Applications, Prentice Hall, 2nd edition, 2001.
[4]
N. L. Allinger, “Conformational analysis. 130. MM2. A hydrocarbon force field utilizing V1 and V2 torsional terms,” Journal of the American Chemical Society, vol. 99, no. 25, pp. 8127–8134, 1977.
[5]
O. Q. Munro and L. Mariah, “Conformational analysis: crystallographic, mole-cular mechanics and quantum chemical studies of C-H...O hydrogen bonding in the flexible bis(nosylate) derivative of catechol,” Acta Crystallographica B: Structural Science, vol. 60, no. 5, pp. 598–608, 2004.
[6]
J. C. Burley, R. Gilmour, T. J. Prior, and G. M. Day, “Structural diversity in imidazolidinone organocatalysts: a synchrotron and computational study,” Acta Crystallographica C: Crystal Structure Communications, vol. 64, no. 1, pp. o10–o14, 2007.
[7]
H. Novoa De Armas, E. Ruiz Reyes, E. Salfrán Solano, M. Suárez Navarro, and N. Blaton, “Methyl [(1E)-(4-methoxy-phen-yl)methyl-eneamino]acetate,” Acta Crystallographica E: Structure Reports Online, vol. 63, no. 3, Article ID fj2002, pp. o1459–o1461, 2007.
[8]
X-ray Crystallography Lab., National Research Center of Egypt (NRC), http://www.xrdlab-nrc-eg.org/.
[9]
Enraf-Nonius, COLLECT, Nonius BV, Delft, The Netherlands, 1998.
[10]
Z. Otwinowski and W. Minor, “Processing of X-ray diffraction data collected in oscillation mode,” Methods in Enzymology, vol. 276, pp. 307–326, 1997.
[11]
G. M. Sheldrick, “A short history of SHELX,” Acta Crystallographica A: Foundations of Crystallography, vol. 64, no. 1, pp. 112–122, 2007.
[12]
G. M. Sheldrick, SHELXS-97-A Program For Crystal Structure Determination, University of G？ttingen, G？ttingen, Germany, 1997.
[13]
S. Mackay, C. J. Gilmore, C. Edwards, N. Stewart, and K. Shankland, MaXus Computer Program For the Solution and Refinement of Crystal Structures, Japan & the University of Glasgow, Madison, Wis, USA, 1999.
[14]
L. J. Farrugia, “ORTEP-3 for windows—a version of ORTEP-III with a graphical user interface (GUI),” Journal of Applied Crystallography, vol. 30, no. 5, p. 565, 1997.
[15]
K. Brandenburg, DIAMOND Software, Crystal Impact GbR, Bonn, Germany, 2012.
[16]
J. D. Gans and D. Shalloway, “Qmol: a program for molecular visualization on Windows-based PCs,” Journal of Molecular Graphics and Modelling, vol. 19, no. 6, pp. 557–609, 2001.
[17]
HyperChem (TM) Professional 7. 51, Hypercube, Inc., 1115 NW 4th Street, Gainesville, Florida 32601, USA.
[18]
N. L. Allinger and Y. H. Yuh, Quantum Chemistry Program Exchange, Bloomington, Indiana, Program No. 395, Molecular Mechanics, Burkert, U.; Allinger, N.L., Ed., ACS Monograph 177, American Chemical Society, Washington, DC, USA, 1982.
[19]
J.-H. Lii and N. L. Allinger, “Molecular Mechanics. The MM3 force field for hydrocarbons. 3. The van der Waals' potentials and crystal data for aliphatic and aromatic hydrocarbons,” Journal of the American Chemical Society, vol. 111, no. 23, pp. 8576–8582, 1989.
[20]
A. Chandramohan, D. Gayathri, D. Velmurugan, K. Ravikumar, and M. A. Kandhaswamy, “1,3,7-Trimethylxanthenium 2,4,6-trinitrophenolate,” Acta Crystallographica E: Structure Reports Online, vol. 63, no. 5, pp. o2495–o2496, 2007.
