Matrix metalloproteinase inhibitors (MMPi) utilize zinc-binding groups (ZBGs) to chelate the catalytic Zn(II) ion resulting in enzyme inhibition. Adapting findings from the literature of Zn(II) ion sensors, we previously reported chelating sulfonamide inhibitors of MMP-2, some of which showed excellent selectivity over other gelatinases (MMP-9). Herein, we greatly expand our investigation of chelating sulfonamides as MMP inhibitors (MMPi) with the synthesis and screening of several new libraries consisting of 2-phenyl-7-sulfonamidobenzimidazole, 2-phenyl-7-sulfonamidobenzoxazole, 7-sulfonamidobenzimidazole, 7-sulfonamidobenzoxazole, and 2-(2-sulfonamidophenyl)-quinoline ZBG derivatives. A novel microwave irradiation synthetic procedure was utilized to rapidly and efficiently prepare these molecules. To better understand the coordination chemistry underlying these ZBGs, crystal structures of representative molecules with several first row transition metals were determined and differences in coordination preferences were considered. Surprisingly, only compounds with the 2-phenyl-7-sulfonamidobenzimidazole ZBG showed inhibition of MMP-2, suggesting that the specific structure of the ZBG can have a pronounced effect of inhibitory activity.