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A rapidly growing resistance of Candida spp. requires a search for bioactive compounds with fungicidal or fungistatic activity. In this context a characteristics and comparison of antifungal properties of 19 sulfone derivatives were conducted. MICs of the Compounds were determined using the M27-A3 protocol following CLSI recommendations. The SAP expression was analyzed using RT-PCR; relative quantification was normalized against ACT1 in cells grown in YEPD and on Caco-2. 79 % of sulfone derivatives (15 out of 19) exhibited an activity against Candida albicans in the tested concentrations. While the addition of both chlorine and bromine atoms to halogenomethylsulfonyl groups stimulates sulfone's antifungal activity, a chlorine atom more effectively up-regulates antifungal properties of the tested sulfones. The insertion of a fluorine atom has a binary effect on antifungal properties of the tested sulfones. The fluorine atom enhances anti- Candida properties when introduced to the aromatic ring, while its presence in halogenomethylsulfonyl group generally lowers the Compound's efficiency. The deletion of particular SAP genes resulted in an increased susceptibility of C. albicans toward sulfones indicating the role of this gene family in resistance mechanisms. Furthermore, RT-PCR analysis demonstrated that sulfone derivatives inhibit the SAP2 expression but not that of SAP7. [ABSTRACT FROM AUTHOR]

Abstract: Several control experiments were designed to optimize the reaction of 2,3-epoxy-1-propanol with R3Al (R = Me, Et or i Bu) and to probe for the nature of aluminium-bound alkyl groups that influence the reactivity and selectivity. The reported studies revealed that the Et3Al mediated reaction leads to the C-2 product in contrast to the well-known C-3 substitution promoted by Me3Al. [Copyright &y& Elsevier]

Formylation of ansa[4]-ferrocene, obtained through the ruthenium-catalysed olefin metathesis, yields two separable, planar chiral 1,3- and 1,2-ansa-ferrocene aldehydes. Single-crystal X-ray structure analysis reveals that both regioisomers crystallize with spontaneous resolution of the racemate in the chiral P212121 space group with one molecule in the asymmetric unit. The major 1,3-isomer was further transformed into a conjugate with 1,2,3-triazole and uracil using "click" chemistry as the key synthetic step. This inorganic-organic hybrid displays anticancer activity (MCF-7, A549, MDA-MB-231 cell lines) with EC50 values comparable to those for cisplatin.

Since candidiasis is so difficult to eradicate with an antifungal treatment and the existing antimycotics display many limitations, hopefully new sulfone derivatives may overcome these deficiencies. It is pertinent to study new strategies such as sulfone derivatives targeting the virulence attributes of C. albicans that differentiate them from the host. During infections, the pathogenic potential of C. albicans relies on the virulence factors as follows: hydrolytic enzymes, transcriptional factors, adhesion, and development of biofilms. In the article we explored how the above-presented C. albicans fitness and virulence attributes provided a robust response to the environmental stress exerted by sulfones upon C. albicans; C. albicans fitness and virulence attributes are fungal properties whose inactivation attenuates virulence. Our understanding of how these mechanisms and factors are inhibited by sulfones has increased over the last years. As lack of toxicity is a prerequisite for medical approaches, sulfones (non-toxic as assessed in vitro and in vivo) may prove to be useful for reducing C. albicans pathogenesis in humans. The antifungal activity of sulfones dealing with these multiple virulence factors and fitness attributes is discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Reactions between O 2 and organometallics with non-redox-active metal centers have received continuous interest for over 150 years, although significant uncertainties concerning the character and details of the actual mechanism of these reactions persist. Harnessing dinuclear three-coordinate alkylzinc derivatives of an N,N-coupled bis(β-diketimine) proligand (LH 2 ) as a model system, we demonstrate for the first time that a slight modification of the reaction conditions might have a dramatic influence on the oxygenation reaction outcomes, leading to an unprecedented variety of products originating from a single reaction system, that is, partially and fully oxygenated zinc alkoxides, zinc alkylperoxides, and zinc hydroxide compounds. Our studies indicate that accessibility of the three-coordinate zinc center by the O 2 molecule, coupled with the lower reactivity of Zn-Me vs. Zn-Et units towards dioxygen, are key factors in the oxygenation process, providing a novel tetranuclear methyl(methoxy)zinc {[L][ZnMe][Zn(μ-OMe]} 2 and zinc ethoxide {[L][Zn(μ-OEt)] 2 } 2 . Remarkably, oxygenation of three-coordinate alkylzinc [L][ZnR] 2 complexes at ambient temperature afforded a unique hydroxide {[L][Zn(μ-OH)] 2 } 2 . Oxygenation of the [L][ZnEt] 2 complex in the presence of 4-methylpyridine (py-Me) at low temperature led to the isolation of a dinuclear zinc ethylperoxide [L][Zn(OOEt)(py-Me)] 2 , which nicely substantiates the intermediacy of an unstable zinc alkylperoxide in the formation of the subsequent zinc alkoxide and hydroxide compounds. Finally, our investigations provide compelling evidence that a non-redox-active metal center plays a crucial role in the oxygenation process through assisting in single-electron transfer from an M-C bond to an O 2 molecule. Although the oxygenation of zinc alkyls occurs by radical pathways, the reported results stand in clear contradiction to the widely accepted free-radical chain mechanism., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Despite the fact that extensive research has been carried out, the oxygenation of alkyl magnesium species still remains a highly unexplored research area and significant uncertainties concerning the mechanism of these reactions and the composition of the resulting products persist. This case study compares the viability of the controlled oxygenation of alkylmagnesium complexes supported by β-diketiminates. The structural tracking of the reactivity of (N,N)MgR-type complexes towards O 2 at low temperature showed that their oxygenation led exclusively to the formation of magnesium alkylperoxides (N,N)MgOOR. The results also highlight significant differences in the stability of the resulting alkylperoxides in solution and demonstrate that [(BDI)Mg(μ-η 2 :η 1 -OOBn)] 2 (in which BDI=[(ArNCMe) 2 CH] - and Ar=C 6 H 3 iPr 2 -2,6) can be easily transformed to the corresponding magnesium alkoxide [(BDI)MgOBn] 2 at ambient temperature, whilst [( F3 BDI)Mg(μ-OOtBu)] 2 (in which F3 BDI=[(ArNCMe) 2 CH] - and Ar=C 6 H 2 F 3 -2,4,6) is stable under similar conditions. The observed selective oxygenation of (N,N)MgR-type complexes to the corresponding (N,N)MgOOR alkylperoxides strongly contradicts the widely accepted radical-chain mechanism for the oxygenation of the main-group-metal alkyls. Furthermore, either the observed transformation of the alkylperoxide [(BDI)MgOOBn] 2 to the alkoxide [(BDI)MgOBn] 2 as well as the formation of an intractable mixture of products in the control reaction between the alkylperoxide [( F3 BDI)MgOOtBu] 2 and the parent alkylmagnesium [( F3 BDI)MgtBu] complex are not in line with the common wisdom that magnesium alkoxide complexes' formation results from the metathesis reaction between MgOOR and Mg-R species. In addition, a high catalytic activity of well-defined magnesium alkylperoxides, in combination with tert-butyl hydroperoxide (TBHP) as an oxygen source, in the epoxidation of trans-chalcone is presented., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)