Silver is one of the noble metals, which has been used not only as money, jewelry, ornaments, and kitchen utensils, but also as a medicinal material. The efficacy of silver nitrate as a antimicrobial agent has been known since the 19th century, and it has been in wound care for over 150 years[1], and it is still used today. In 1968, silver sulfadiazine was introduced as antimicrobial to treat Pseudomonas infection in burns [2], making the beginning of the true revival of silver antibiotics[3]. Nowadays, silver sulfadiazine is one of the most effective and commonly used topical agent for outpatients, widely used for the treatment of second- and third-degree burns[4]. Recently, several silver(I) complexes with antibacterial activity which can inhibit the growth of bacteria or fungi have been reported[[5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18]]. With the increase cancer patients, antitumor activity of silver(I) complexes is also concerned[[5], [6], [7], [8],[19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32]]. Some silver-triphenylphosphine complexes are among the many antimicrobial or anticancer silver compounds[[25], [26], [27], [28], [29], [30], [31], [32],48]. As a mitochondrion-targeted ligand, triphenylphosphine, can penetrate the mitochondrial membrane for its lipophilicity and stable cationic charge[28,33]. Several complexes containing mitochondria targeting group triphenylphosphine have been reported, for example, Zhou W et al. introduced one mitochondrion-targeting copper complex which could penetrate the cytoplasmic and mitochondrial membranes of cancer cells and affected the mitochondrial membrane potential[34]. Gao Z et al. reported Sm-TCPP-Pt/TPP nanosheets with the ability to target mitochondria and induce tumor cell apoptosis by the generating ROS close to mitochondria[35]. Banti et al. reported three Ag(I) complexes containing mefenamato and pnictogen derivatives ligand and their micelles strongly interacted with the mitochondrion membrane, resulting in apoptosis[27].

Tolfenamic acid (Htolf) and ibuprofen (Hibu) are non-steroidal anti-inflammatory drugs (NSAIDs), and used as anti-inflammatories, analgesics and antipyretic drugs. In addition, NSAIDs can lower the risk and mortality of several cancers[36]. Recently, it was found that the metal complexes of NSAIDs have antitumor activity, and when compared to free NSAIDs, the metal-NSAIDs complexes show a number of biological activities[25]. In this context, there are number of studies on synthesis and anticancer activity of metal-complexes with tolfenamic acid and ibuprofen as ligands[23,[37], [38], [39], [40], [41]], some of these are more effective than cisplatin or carboplatin. Based on these studies we decided to introduce triphenylphosphine into the system of Ag(I)/tolfenamic acid or Ag(I)/(S)-(+)-ibuprofen. Finally, we obtained two Ag(I) complexes: [Ag(tpp)2(tolf)] (1) and [Ag(tpp)2(ibu)] (2) where tpp = triphenylphosphine, tolf = deprotonated tolfenamic acid, ibu = deprotonated (S)-(+)-ibuprofen (Scheme 1). Herein, we describe the synthesis, structures, and biological properties of the two Ag(I) complexes. Both the complexes were characterized by FT-IR, 1H NMR, 13C NMR, and single-crystal X-ray diffraction. The interactions of the two Ag(I) complexes with DNA/BSA were investigated by UV or fluorescence spectra. The cytotoxic potency in vitro of 1 and 2 against A549, HeLa, HepG-2, and MCF-7 cancer cells was evaluated. The reactive oxygen species (ROS)-mediated apoptosis was studied by fluorescence microscopy. The induction of apoptosis and changes in cell cycle arrest were measured by flow cytometry.