Tailoring antibacteria agents: Sulfonamide-based dinuclear and 1D polymer Cu(II) complexes

Abstract Starting from two bioactive sulfonamide-based ligands (HL1: 4-amino- N -(2,6-dimethoxy-4-pyrimidinyl)benzenesulfonamide; HL2: 4-amino- N -(4-methyl-2-pyrimidinyl)benzenesulfonamide) and Cu(II) salts ([Cu 2 (Ac) 4 ] and CuCl 2 , Ac = acetate), the synthesis of [Cu 2 (Ac) 2 (L1) 2 ] ( 1 ) and [Cu 2 (L2) 4 ] ( 2 ) and {Cu(L1) 2 (bipy)} n ·2 n H 2 O· n (CH 3 OH) ( 1′ ) (bipy = 4,4′-bipy) architectures with potential antibiotic and antiseptic activities is reported. To confirm the possibility to fulfill specific criteria and ultimately combine both properties, the bioactive sulfonamide-based complexes are structurally, electrochemically and magnetically characterized. Depending on the synthesis conditions, the Cu:sulfonamide stoichiometry and Cu···Cu communication are first varied by controlling the chemical nature of the ancillary ligand (Ac or bipy). Then, electrochemistry data support the stability of 1 and 2 dinuclear complexes, and 1′ 1D polymer, a prerequisite for their bioactivity in solution. Interestingly, the synthesis leads to architectures where the (SO 2 -Ph-NH 2 ) moiety which is responsible for the antibacterial activity remains non-coordinated in the vicinity of Cu(II) antiseptic ions. Magnetic susceptibility measurements combined to multireference wavefunction ab initio calculations evidence a rather strong antiferromagnetic behavior in the dinuclear compounds ( H  =  − 2 JS 1 S 2 , 2 J 1  = −307.8 cm −1 in 1 , 2 J 2  = −63.2 cm −1 in 2 ) whereas chain 1′ is paramagnetic. The cooperativity quantified by the hopping integral which is available from the ab initio calculations of the exchange coupling constant is reduced by a factor of two when the number of sulfonamide ligands increases in complexes 1 and 2 . In contrast, it is negligibly small in the 1D polymer 1′ . These characterized bioactive sulfonamide-based Cu(II) compounds appear as promising targets, complying with the structural and electronic expectations for antibacterial and antiseptic purposes. Finally, the antibacterial activity studies question the prerequisite for cooperative metal centers to rationally design antibacterial agents since the minimum inhibitory concentration in the paramagnetic chain 1′ is greatly reduced as compared to antiferromagnetic complexes 1 and 2 .