Synthesis and Vibrational Studies of an AZT Derivative: Bis(3´-Azido-3´-Deoxythymidin-5’-yl) Carbonate. Its Interaction with Copper (II)

WILLIAMS PAM; ETCHEVERRY, S. B.; PIRO, O. E.; CASTELLANO, E. E.; RAVIOLO, M; BRIÑÓN, M

Buenos Aires, Argentina

Workshop; International Workshop on Infrared Spectroscopy Applied to Biological and Biomimetic Systems: From the Isolated Molecule to the Cell,; 2007

Synthesis and vibrational studies of an AZT derivative: bis(3´-azido-3´-deoxythymidin-5’-yl) carbonate. Its interaction with copper (II)   Williams, P.A.M.1, Etcheverry, S.B.1,2, Piro, O. E.3, Castellano, E.4, Raviolo, M.5, Briñón, M5.   1 CEQUINOR (Centro de Química Inorgánica), 2 Cátedra de Bioquímica Patológica, 3  Departamento de Física and Instituto IFLP (CONICET), Facultad de Ciencias Exactas, Universidad Nacional de La Plata. 47 y 115 (1900) La Plata, Argentina. 4  Instituto de Física de São Carlos, Universidade de São Paulo, 13560 São Carlos (SP), Brazil. 5 Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina. corresponding_author@email: williams@quimica.unlp.edu.ar   Zidovudine (AZT) is a synthetic analog of natural nucleosides have been used extensively in AIDS treatments. We report herein the synthesis, crystal structure and the vibrational characterization of a new derivative of AZT, the organic carbonate of AZT, bis (3’-azido-3’-deoxythymidin-5’-yl) carbonate [(AZT-O)2C=O] (Figure 1). The structure was determined by single crystal X-ray diffraction methods. The substance crystallizes in the tetragonal space group P41212 with a=b=15.284(1), c=21.695(1) Å, and Z=8 molecules per unit cell. Thymine=thymine base pairing between neighboring molecules in the lattice gives rise to H-bonded polymeric chains perpendicular to the crystal c-axis.     Figure 1. View of dimeric bis(3´-azido-2’,3´-dideoxythymidine) carbonate showing the thymine=thymine base pairing (in dashed lines) H-bonding neighboring molecules along the chain.   The copper complex obtained with its hydrolysis product, [Cu(ROCOO)OH(H2O)4], with (R= AZT(-OH)) is also reported. The new compound corresponds to a mixed carbonate derived from AZT and Cu(II). The vibrational FTIR and Raman studies show that the ligand splits into two moieties when it interacts with Cu(II) and coordinates to the metal ion through the anionic carbonate group generated in the reaction, while the bands of the free ligand n(C=O) and n(O-C-O) disappeared upon complexation.1,2 The strong antisymmetric stretching of azide group at 2106 cm-1 and the vibrational modes of the thymine moiety remain unchanged when the complex is formed. These results are indicative that the metal center does not interact with the azide and the thymine residues.   References   1.              B. Smith, Infrared Spectral Interpretation. A Systematic Approach. CRC-Press, Boca Raton, 1999, pp. 114-115. 2.              G.B. Deacon, R.J. Phillips, Coord. Chem. Rev. 33 (1980) 227-250.