454 Full Paper Received: 14 November 2010 Revised: 4 January 2011 Accepted: 19 January 2011 Published online in Wiley Online Library: 28 April 2011 (wileyonlinelibrary.com) DOI 10.1002/aoc.1786 Synthesis, spectroscopic, thermal and biological aspects of drug-based copper(II) complexes Paresh N. Patel, Darshana J. Patel and Hasmukh S. Patel ∗ A series of novel complexes of the type Cu(II)(L n ) 2 (H 2 O) 2 ] • xH 2 O [where L n = L 1–4 , these ligands being described as: L 1 , 2-({4-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-ylsulfonyl]phenylimino}methyl)phenol, x = 1; L 2 , 2-({4-[6,7-dihydrothieno[3,2-c] pyridin-5(4H)-ylsulfonyl]phenylimino}methyl)-5-(methoxy)phenol, x = 2; L 3 , 5-chloro-2-({4-[6,7-dihydrothieno[3,2-c]pyridin- 5(4H)-ylsulfonyl]phenylimino}methyl)phenol, x = 2; and L 4 , 5-bromo-4-chloro-2-({4-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)- ylsulfonyl]phenylimino} methyl)phenol, x = 1] was investigated. They were characterized by elemental analysis, IR, 1 H-NMR, 13 C-NMR and electronic spectra, magnetic measurements and thermal studies. The FAB-mass spectrum of [Cu(II)(L 1 ) 2 (H 2 O) 2 ] • H 2 O was determined. A magnetic moment and reflectance spectral study revealed that an octahedral geometry could be assigned to all the prepared complexes. Ligands (L n ) and their metal complexes were screened for their in vitro antibacterial activity against Bacillus subtillis, Pseudomonas aeruginosa, Escherichia coli and Serratia marcescens bacterial strains. Kinetic parameters such as order of reaction (n), the energy of activation (E a ), the pre-exponential factor (A), the activation entropy (S  = ), the activation enthalpy (H  = ) and the free energy of activation (G  = ) are reported. Copyright c  2011 John Wiley & Sons, Ltd. Keywords: Cu(II) complexes; spectroscopic; Freeman-Carroll method; antibacterial activity Introduction Compounds 4,5,6,7-tetrahydrothieno[3,2-c]pyridine and 4- aminobenzene-1-sulfonylchloride are extensively studied com- pounds owing to their wide spectrum of bioactivities. Despite numerous attempts to develop new structural prototypes in the search for more effective antimicro- bials, N-benzylidene-4-{6,7-dihydrothieno[3,2-c] pyridin-5(4H)- ylsulfonyl}aniline and its complexes comprise one of the most versatile classes of compounds against microbes and therefore are important components of molecules in drug discovery. A literature survey revealed that 4,5,6,7-tetrahydrothieno[3,2- c]pyridine and its various derivatives, such as clopidogrel [1,2] and ticlopidine, [3,4] are acknowledged to show noncyto- toxic and complement inhibition properties. A series of substituted 4,5,6,7-tetrahydrothieno[3,2-c]pyridines (THTPs) was synthesized and evaluated for human phenylethanolamine N-methyltransferase (hPNMT) inhibitory potency and affinity for the α 2 -adrenoceptor. [5] Various sulfonamide derivatives of 4-aminobenzene-1-sulfonylchloride like benzo[d]-isothiazol- 3-one benzenesulfonamides are also well known to have antimicrobial activity. [6] These medicinal properties render the two compounds useful structural units in drug re- search. These findings prompted us to synthesize benzylidene derivatives of 4,5,6,7-tetrahydrothieno[3,2-c] pyridine as part of our ongoing research program aiming at the synthe- sis of their various complexes for biological evaluation. Herein, we report the synthesis of a novel series of com- plexes of N-benzylidene-4-{6,7-dihydrothieno[3,2-c]pyridin-5(4H)- ylsulfonyl}aniline derivatives and investigation of their antibacte- rial activity profile. From this point of view, the objective of the present communication comprises the synthesis of a se- ries of new compounds. The synthetic approach is shown in Scheme 1. Many drugs possess modified pharmacological and toxico- logical properties when administered in the form of metallic complexes. Probably the most widely studied cation in this re- spect is Cu(II), since a host of low-molecular-weight copper complexes have been proven beneficial against diseases such as tuberculosis, rheumatoid, gastric ulcers and cancers. [7 – 10] There is a continuing interest in metal complexes of Schiff bases because of the presence of nitrogen and oxygen donor atoms in the backbones of these ligands. This means that they readily coordinate with a wide range of transition metal ions, yielding stable and intensely colored metal complexes, some of which have been shown to exhibit interesting physi- cal and chemical properties [11 – 13] and potentially useful biological activities. [14 – 16] Thermal analysis techniques are extensively used in studying the thermal behavior of metal complexes. [17 – 19] Thermogravimetry is a process in which a substance is decomposed in the presence of heat, which causes bonds of the molecules to be broken. [20,21] The present work describes the synthetic, thermal, spectroscopic aspects and anti-bacterial activity of new copper complexes [Cu(II)(L n ) 2 (H 2 O) 2 ] • xH 2 O. ∗ Correspondence to: Hasmukh S. Patel, Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar-388120, Gujarat, India. E-mail: drhspatel786@yahoo.com Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar-388120, Gujarat, India Appl. Organometal. Chem. 2011, 25, 454–463 Copyright c  2011 John Wiley & Sons, Ltd.