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Antibiotic resistance is a growing global health concern. Colistin is one of the last-resort antibiotics that treats multidrug-resistant (MDR) Gram-negative bacterial infection. However, bacteria resistant to colistin have become increasingly prevalent. Using a bacterial whole-cell screen of a fragment-based library, one compound was discovered to resensitize MDR

Thermostable direct hemolysin (TDH) of Vibrio parahemolyticus is a membrane-damaging pore-forming toxin with potent cytolytic/cytotoxic activity. TDH exists as a tetramer consisting of protomers with a core β-sandwich domain, flanked by an 11-amino acid long N-terminal region (NTR). This NTR could not be modeled in the previously determined crystal structure of TDH. Moreover, the functional implication of NTR for the membrane-damaging action of TDH remains unknown. In the present study, we have explored the implications of NTR for the structure-function mechanism of TDH. Our data show that the presence of NTR modulates the physicochemical property of TDH in terms of augmenting the amyloidogenic propensity of the protein. Deletion of NTR compromises the binding of TDH toward target cell membranes and drastically affects the membrane-damaging cytolytic/cytotoxic activity of the toxin. Mutations of aromatic/hydrophobic residues within NTR also confer compromised cell-killing activity. Moreover, covalent trapping of NTR, via an engineered disulfide bond, against the core β-sandwich domain also abrogates the cytolytic/cytotoxic activity of TDH. This observation suggests that an unrestrained configuration of NTR is crucial for the membrane-damaging action of TDH. On the basis of our study, we propose a model explaining the role of NTR in the membrane-damaging function of TDH.

In addition to the zirconation of benzylic hydrocarbons, Ar−CH3, by di-n-butylzirconium diethoxide and the ensuing C−C bond formation from (Ar−CH2)2Zr(OEt)2 to yield Ar−CH2−CH(ZrH(OEt)2)−Ar, it has now been found that Bu2Zr(OEt)2 in ethers can also cleave the C−C bond in bibenzylic hydrocarbons, Ar−CH2−CH2−Ar‘, into benzylic zirconium fragments, (Ar−CH2)(Ar‘−CH2)Zr(OEt)2, as fostered by LiOEt and donor solvents. The role of SET processes in such C−C bond cleavages and the potential relevance to practical alkane metathesis are considered.

The mechanism of the rearrangement of diorganylzirconium dialkoxides, such as R1(R2CH2)Zr(OEt)2, into organylzirconium hydride alkoxides of the type R1R2CHZr(OEt)2H, has been investigated as a function of the R1 and R2 substituents and been found to involve optimally an intramolecular migration of R1 to an sp3-hybridized C−H center. A remarkably rapid transfer hydrozirconation between Bun2Zr(OEt)2 and the olefin RCHCH2 now permits the synthesis of (RCH2CH2)2Zr(OEt)2, whose rearrangement offers a route to the linear olefin dimer R(CH2)4R.

Benzylic hydrocarbons of the types Ar−CH3 and Ar2CH2 undergo zirconation at their benzylic C−H bonds by Bun2Zr(OEt)2 at room temperature in Lewis basic solvents and catalyzed by lithium ethoxide. Upon heating, such benzylic organozirconium derivatives can undergo C−C bond formation, either intermolecularly or intramolecularly, with the elimination of zirconium(IV) hydrides of the type H2Zr(OEt)2. Such oxidative dimerizations or cyclizations are exemplified by the conversion of toluene into trans-stilbene or the formation of 9,10-dihydrophenanthrene from 2,2 ‘-dimethylbibenzyl.

The aerial reaction of 2,2'-dihydroxyazobenzene (H 2 L) with bis(acetylacetonato)oxovanadium(IV) in methanol affords binuclear V v 2 O 3 L 2 . In the presence of KOH, KV v O 2 L.1.5H 2 O is isolated. Dilute acids convert VO 2 L. to V 2 O 3 L 2 via V v O(OH)L. The electronic and IR spectra of the complexesare described. In crystalline KVO 2 L.1.5H 2 O, the vanadium(V) atom has square pyramidal geometry. The base is formed by coordinated ONO atoma of L 2- and an oxo oxygen atom

The reaction of the tris(arylazo oximato)iron(II) anion, Fe(RL) 3 - (R=Me, Ph, p-MeC 6 H 4 ), with Cu(MeCN) 4 + in dichloromethane under air affords the trinuclear complex Cu II Fe II 2 (RL) 6 . In the presence of PPh 3 in the reaction mixture, the binuclear complex Cu I Fe II (RL) 3 (PPh 3 ) is isolated. The X-ray structures of CuFe(MeL) 3 (PPh 3 ) and CuFe 2 (PhL) 6 .2CH 2 Cl 2 are reported. In both complexes the Fe(RL) 3 - fragment acts as a facially disposed tridentate oximato-O 3 ligand

In the title families the ONO ligands are deprotonated forms of N-(2-hydroxyphenyl)salicylaldimine (H 2 amp), 2,2'-dihydroxyazobenzene (H 2 azp), N-(2-carboxyphenyl)salicylaldimine (H 2 amc), or 2-hydroxy-2'-carboxy-5-methylazobenzene (H 2 azc). The ON ligand is deprotonated 8-quinolinol (Hhq), and the NN ligands are 2,2'- bipyridine (bpy) or 1,10-phenanthroline (phen). Reaction of VO(acac) 2 with a mixture of H 2 amp and bpy or Hhq in methanol affords V IV O(amp)(bpy) or V V O(amp)(hq)