Sulfur-Containing Ferrocenyl Alcohols and Oximes: New Promising Antistaphylococcal Agents by Danijela Ilic ´ a ), Ivan Damljanovic ´ b ), Dragana Stevanovic ´ b ), Mirjana Vukic ´evic ´ c ), Polina Blagojevic ´ d ), Niko Radulovic ´* d ) and Rastko D. Vukic ´evic ´* b ) a )Technical Faculty Kosovska Mitrovica, University of Pris ˇtina, Kneza Milos ˇa 7, RS-38220 Kosovska Mitrovica b ) Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovic ´a 12, RS-34000 Kragujevac (phone: þ 38134300286; fax: þ 38134335040; e-mail: vuk@kg.ac.rs) c )Department of Pharmacy, Faculty of Medicine, University of Kragujevac, S. Markovic ´a 69, RS-34000 Kragujevac d )Department of Chemistry, Faculty of Science and Mathematics, University of Nis ˇ, Vis ˇegradska 33, RS-18000 Nis ˇ (phone: þ 381628049210; fax: þ 38118533014; e-mail: nikoradulovic@yahoo.com) A small library containing four different series of new ferrocene derivatives, 2-(alkylsulfanyl)-1- ferrocenylethan-1-ols, 3-(alkylsulfanyl)-1-ferrocenylpropan-1-ols, ( E)- and ( Z)-2-(alkylsulfanyl)-1-fer- rocenylethan-1-one oximes, and ( E)- and ( Z)-3-(alkylsulfanyl)-1-ferrocenylpropan-1-one oximes (36 different compounds in total) was synthesized starting from ferrocene and the corresponding sulfanyl acids. All compounds were spectrally (IR and NMR) and electrochemically characterized. In general, the obtained compounds were found to exhibit very strong antimicrobial activities (broth microdilution assay) against the tested microorganisms (six common human pathogens) . For the majority of the tested compounds, the determined MIC values were either under the 10 mg/ml MIC limit recognized to delimit efficient antimicrobials or were comparable to/lower than those of the used positive controls (tetracycline/nystatin). The most susceptible organism was found to be Staphylococcus aureus with MIC values even reaching 0.001 mg/ml. The presence of CH(OH)(CH 2 ) n S  and CH(¼NOH)(CH 2 ) n S  (n ¼ 1 or 2) structural fragments seems to be essential for the observed strong activity (introduction of hydroxyimino and alcohol functionalities, instead of the keto function, resulted in a more than 10 5 -fold increase in antistaphylococcal activity in some instances). Nevertheless, a possible influence of the ferrocenyl-core redox chemistry (Fe 2 þ /Fe 3 þ ) should not be disregarded. The studied alcohols exhibited a reversible one-electron redox couple at almost the same position as ferrocene, while the hydroxyimino group conjugated with cyclopentadienyl ring considerably shifted the redox potential of the ferrocene unit in oximes. Introduction. – Over the past few decades, the number and extent of infections caused by multi-drug resistant (MDR) microorganisms has reached an alarming level. The rapidly developing drug resistance and drug side-effects limit the use of a large number of antimicrobial agents. All of this represents a serious challenge to the medical community [1]. Hence, the discovery and development of new antimicrobial agents became an important goal. Certain organometallic compounds offer a particular promise in this respect, because they are kinetically inert, often uncharged, and fairly lipophilic [2]. The metal centers exist in low oxidation states, which limit the danger of CHEMISTRY & BIODIVERSITY – Vol. 9 (2012) 2236 # 2012 Verlag Helvetica Chimica Acta AG, Zürich