The bis-(1,10-phenanthroline)copper(I) complex, [Cu(I)(phen)₂]⁺, was the first copper-based artificial nuclease reported in the literature. The biological and ligand-like properties of sulfonamides make them good candidates for fine-tuning the reactivity of the [Cu(phen)₂] motif with biomolecules. In this context, we developed three novel copper(II) complexes containing the sulfonamides sulfameter (smtrH) and sulfadimethoxine (sdmxH) and (N^N)-bidentate ligands (2,2′-biyridine or 1,10-phenantroline). The compounds were characterized by chemical and spectroscopic techniques and single-crystal X-ray crystallography. When targeting plasmid DNA, the phen-containing compounds [Cu(smtr⁻)₂(phen)] (1) and [Cu(sdmx⁻)₂(phen)] (2) demonstrated nuclease activity even in the absence of reducing agents. Addition of ascorbic acid resulted in a complete cleavage of DNA by 1 and 2 at concentrations higher than 10 μM. Experiments designed to evaluate the copper intermediates involved in the nuclease effect after reaction with ascorbic acid identified at least the [Cu(I)(N^N)₂]⁺, [Cu(I)(sulfa)(N^N)]⁺ and [Cu(I)(sulfa)₂]⁺ species. The compounds interact with DNA via groove binding and intercalation as verified by fluorescence spectroscopy, circular dichroism (CD) and molecular docking. The magnitude and preferred mode of binding are dependent on the nature of both N^N ligand and the sulfonamide. The potent nuclease activity of compounds 1 and 2 are well correlated with their antiproliferative and anti-M. tuberculosis profiles. The results presented here demonstrated the potential for further development of copper(II)-sulfonamide-(N^N) complexes as multipurpose metallodrugs.

双-（1,10-菲咯啉）铜（I）络合物[Cu（I）（phen）₂ ] ⁺是文献中报道的第一种基于铜的人工核酸酶。磺酰胺的生物学和配体性质使其成为微调[Cu（phen）₂ ]基序与生物分子反应性的良好候选者。在这种情况下，我们开发了三种新型的铜（II）配合物，它们分别包含磺酰胺磺胺法（smtrH）和磺胺二甲氧嘧啶（sdmxH）和（N ^ N）双齿配体（2,2'-联吡啶或1,10-菲咯啉）。通过化学和光谱技术以及单晶X射线晶体学对化合物进行表征。当靶向质粒DNA，含啉化合物[铜（SMTR ^- ）₂（苯）]（1）和物[Cu（SDMX ^- ）₂（苯）]（2）证实核酸酶活性甚至在不存在还原剂的。抗坏血酸的加入导致浓度高于10μM的DNA被1和2完全裂解。设计用于评估与抗坏血酸反应后参与核酸酶作用的铜中间体的实验至少鉴定出[Cu（I）（N ^ N）₂ ] ⁺，[Cu（I）（sulfa）（N ^ N）] ⁺和[Cu（I）（sulfa）₂ ] ⁺物种。如荧光光谱，圆二色性（CD）和分子对接所证实的，这些化合物通过凹槽结合和嵌入与DNA相互作用。结合的程度和优选方式取决于N 1 N配体和磺酰胺的性质。化合物1和2的有效核酸酶活性与其抗增殖和抗结核分枝杆菌的特性密切相关。本文介绍的结果证明了进一步开发铜（II）-磺酰胺-（N ^ N）配合物作为多用途金属药物的潜力。