Synthesis, X-ray crystal structure, anti-fungal and anti-cancer activity of [Ag 2 (NH 3 ) 2 (salH) 2 ] (salH 2 ¼ salicylic acid) Barry Coyle a , Malachy McCann a, * , Kevin Kavanagh b , Michael Devereux c , Vickie McKee d , Nijhuma Kayal d , Denise Egan e , Carol Deegan e , Gregory J. Finn f a Chemistry Department, National University of Ireland Maynooth, Maynooth, Co. Kildare, Ireland b Biology Department, National University of Ireland Maynooth, Maynooth, Co. Kildare, Ireland c Dublin Institute of Technology, Cathal Brugha Street, Dublin, Ireland d Chemistry Department, Loughborough University, Loughborough, Leics., LE11 3TU, UK e Department of Applied Science, Institute of Technology, Tallaght, Dublin 24, Ireland f Cancer Research Program, Beth Israel Deaconess Medical Centre, Harvard Institutes of Medicine, Harvard Medical School, Boston, MA, USA Received 21 January 2004; received in revised form 1 April 2004; accepted 26 April 2004 Available online 15 June 2004 Abstract [Ag 2 (NH 3 ) 2 (salH) 2 ] (salH 2 ¼ salicylic acid) was synthesised from salicylic acid and Ag 2 O in concentrated aqueous NH 3 and the dimeric Ag(I) complex was characterised using X-ray crystallography. The complex is centrosymmetric with each metal coordinated to a salicylate carboxylate oxygen and to an ammonia nitrogen atom in an almost linear fashion. The two [Ag(NH 3 )(salH)] units in the complex are linked by an Ag–Ag bond. Whilst metal-free salH 2 did not prevent the growth of the fungal pathogen Candida albicans [Ag 2 (NH 3 ) 2 (salH) 2 ], [Ag 2 (salH) 2 ] and some simple Ag(I) salts greatly inhibited cell reproduction. SalH 2 , [Ag 2 (NH 3 ) 2 (salH) 2 ] [Ag 2 (salH) 2 ] and AgClO 4 produced a dose-dependent cytotoxic response against the three human derived cancer cell lines, Cal-27, Hep-G2 and A-498, with the Ag(I)-containing reagents being the most effective. Ó 2004 Elsevier Inc. All rights reserved. Keywords: Silver(I); Salicylate; X-ray structure; Anti-fungal; Anti-cancer 1. Introduction In our efforts to develop new metal-based drugs for inhibiting the growth of the fungal pathogen Candida albicans, and also for deterring the proliferation of mammalian cancer cells, the most effective metal com- plex to emerge to date is the Ag(I) complex [Ag(phen- dio) 2 ]ClO 4 (phendio ¼ 1,10-phenanthroline-5,6-dione) [1]. The complex has a minimum inhibitory concentra- tion (MIC) against C. albicans of 0.5 lg cm À3 (0.3 lM) and tests on cultured human cancer cells produced an IC 50 (the concentration that inhibited growth by 50%) value of 0.025 lg cm À3 (0.40 lM). These findings for the Ag(I) complexes were a marked improvement on values obtained using other transition metals complexed by phendio or 1,10-phenanthroline [1–3] and have promp- ted investigations into the preparation, characterisation and testing of other Ag(I) complexes. The present paper details the synthesis, X-ray crystal structure and bio- logical activity of the dimeric Ag(I) complex [Ag 2 (NH 3 ) 2 (salH) 2 ] (salH 2 ¼ salicylic acid). 2. Results and discussion The method used for preparing [Ag 2 (NH 3 ) 2 (salH) 2 ] was quite similar to that employed for the preparation of the known non-amine analogue [Ag 2 (salH) 2 ] [4–6]. [Ag 2 (NH 3 ) 2 (salH) 2 ] was obtained from a suspension of Ag 2 O in water to which was added concentrated aque- ous NH 3 followed by salicylic acid (salH 2 ). On the other hand, [Ag 2 (salH) 2 ] was prepared in an 80:20 etha- nol:water solvent mixture to which was added salH 2 , * Corresponding author. Tel.: +353-1-7083767; fax: 353-1-7083815. E-mail address: mmcann@may.ie (M. McCann). 0162-0134/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.jinorgbio.2004.04.016 Journal of Inorganic Biochemistry 98 (2004) 1361–1366 www.elsevier.com/locate/jinorgbio JOURNAL OF Inorganic Biochemistry