Ligand-exchangeability of 2-coordinate phosphinegold(I) complexes with AuSP and AuNP cores showing selective antimicrobial activities against Gram-positive bacteria. Crystal structures of [Au(2-Hmpa)(PPh(3))] and [Au(6-Hmna)(PPh(3))] (2-H(2)mpa=2-mercaptopropionic acid, 6-H(2)mna=6-mercaptonicotinic acid).
Selective and effective antimicrobial activities against Gram-positive bacteria (B. subtilis and/or S. aureus) were found in 2-coordinate gold(I)-PPh(3) complexes with AuSP and AuNP cores, i.e. [Au(L)(PPh(3))] (HL=2-H(2)mna [H(2)mna=mercaptonicotinic acid] 3, D-H(2)pen [H(2)pen=penicillamine] 4, D,L-H(2)pen 5, 4-H(2)mba [H(2)mba=mercaptobenzoic acid] 8, Hpz [Hpz=pyrazole] 9, Him [Him=imidazole] 10, 1,2,3-Htriz [Htriz=triazole] 11, 1,2,4-Htriz 12, Htetz [Htetz=tetrazole] 13), whereas no activity was observed in 2-coordinate AuSP core complexes [Au(2-Hmba)(PPh(3))] 6 and [Au(3-Hmba)(PPh(3))] 7. The two novel AuSP core complexes, [Au(2-Hmpa)(PPh(3))] [H(2)mpa=mercaptopropionic acid] 1 and [Au(6-Hmna)(PPh(3))] 2, were prepared and characterized by elemental analysis, FT-IR, TG/DTA, and ((31)P, 1H and 13C) NMR spectroscopy. The crystal structures of 1 and 2 were determined as a supramolecular arrangement of the 2-coordinate AuSP core. Both 1 and 2 significantly showed antibacterial activities. As a model reaction of phosphinegold (I) complexes with the cysteine residue in the biological ligands, we examined if the ligand exchange reactions of the aromatic anions L(1)(-) in [Au(L(1))(PPh(3))] (HL(1)=6-H(2)mna 2, 2-H(2)mna 3, 2-H(2)mba 6, Hpz 9, Him 10, 1,2,3-Htriz 11, 1,2,4-Htriz 12) with aliphatic thiols HL(2) (HL(2)=2-H(2)mpa, D-H(2)pen) occurred under the mild conditions and, also, if the 'reverse' reactions, namely, the ligand exchange reactions of the thiolate anions in [Au(2-Hmpa)(PPh(3))] 1, [Au(D-Hpen)(PPh(3))] 4 and [Au(2-Hmba)(PPh(3))] 6 with the free ligands HL(1) took place under similar conditions. In this work, a relationship of the ligand-exchangeability among 2-coordinate gold(I) complexes (1-4, 6, 9-12) was revealed. Complex 6 was substitution-inert, whereas complexes 1-4 and 9-12 were substitution-labile. The ligand-exchangeability of Au-S and Au-N bonds in the 2-coordinate phosphinegold(I) complexes with AuSP and AuNP cores to form new AuSP cores, with retention of the Au-P bond, was closely related to the observed activities against Gram-positive bacteria, and the ease of the ligand-exchange reaction was strongly related to the intensity of the activities.
Nomiya
Kenji
K
Department of Materials Science, Faculty of Science, Kanagawa University, Tsuchiya, Hiratsuka, Kanagawa 259-1293, Japan. nomiya@chem.kanagawa-u.ac.jp
Yamamoto
Satoshi
S
Noguchi
Ryusuke
R
Yokoyama
Hironari
H
Kasuga
Noriko Chikaraishi
NC
Ohyama
Kei
K
Kato
Chieko
C
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D006046:Gold / Q000737:chemistry* / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009584:Nitrogen / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D010720:Phosphines / Q000737:chemistry* / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013818:Thermogravimetry / Q000379:methods
D000900:Anti-Bacterial Agents; D008024:Ligands; D009942:Organometallic Compounds; D010720:Phosphines; D013438:Sulfhydryl Compounds; D006046:Gold; C044646:phosphine; D009584:Nitrogen