Synthesis, characterization and antibacterial applications of pyrazolyl-sulfonamides and their palladium complexes

A series of pyrazolyl sulfonamide compounds were prepared by a multi-step procedure involving preparation of phenyl pyrazolyl compounds (C1, C2) and their chlorosulfonated derivatives (C3-C5), which were then converted to sulfonamides (L1-L6). Complexes of L1-L6 with palladium(ii) show the standard trans square-planar coordination environment for the six complexes (1-6). All products were prepared in moderate to high yield (61-81%). All compounds were successfully characterized by NMR spectroscopy, IR spectroscopy, mass spectrometry and in one case single X-ray crystallography. Conversion of C1 and C2 to C3-C5 is governed by steric hindrance on the pyrazolyl group as sulfonation of the phenyl only is observed for Bu-t groups (C4), whereas for Me groups sulfonation of the pyrazolyl is observed C3 as well as phenyl ring for C5. Antimicrobial screening was carried out on the compounds using the agar-well diffusion method at varying concentrations of (62.5, 125, 250, 500 and 1000 mu g mL(-1)) on ten (10) bacteria strains. The zone of inhibition for all the compounds are within the ranges of 9.5 mm to 25 mm compared to the control antibiotic, gentamicin that was between 16.5 mm to 36 mm. The compounds L1-L6 generally showed mild to strong antibacterial activity in the zones of inhibition against most Gram negative bacteria strains tested, but no activity against Gram positive bacteria strains Staphylococcus aureus and Enterococcus faecalis, except L4 which showed activity towards Staphylococcus. The palladium(ii) complexes generally showed improved activities for all the bacteria strains studied with 4 exhibiting the most potent in vitro anti-bacterial activity with MICs of 1.046 mu g mL(-1) and 0.237 mu g mL(-1) against Staphylococcus epidermidis and Proteus mirabilis respectively. Theoretical Log P calculation show values between 3.06 and 5.95 for the ligands and between 6.67 and 12.36 for complexes. Suggesting high affinity of these compounds to the lipophilic medium. However, the experimental Log P value gave a different trend, which shows that compounds with sulfonation only on the phenyl ring (L3 (-0.83), L4 (-0.53), 3 (-0.96) and 4 (-0.72)) have high affinity for the hydrophilic medium.

Automated summary

A series of pyrazolyl sulfonamide compounds were successfully synthesized through a multi-step method, forming complexes with palladium(ii). These compounds showed strong antibacterial activity in screening tests, indicating potential medicinal value.