Staphylococcus aureus Exfoliative Toxin E, Oligomeric State and Flip of P186: Implications for Its Action Mechanism.

Staphylococcal exfoliative toxins (ETs) are glutamyl endopeptidases that specifically cleave the Glu381-Gly382 bond in the ectodomains of desmoglein 1 (Dsg1) via complex action mechanisms. To date, four ETs have been identified in different Staphylococcus aureus strains and ETE is the most recently characterized. The unusual properties of ETs have been attributed to a unique structural feature, i.e., the 180° flip of the carbonyl oxygen (O) of the nonconserved residue 192/186 (ETA/ETE numbering), not conducive to the oxyanion hole formation. We report the crystal structure of ETE determined at 1.61 Å resolution, in which P186(O) adopts two conformations displaying a 180° rotation. This finding, together with free energy calculations, supports the existence of a dynamic transition between the conformations under the tested conditions. Moreover, enzymatic assays showed no significant differences in the esterolytic efficiency of ETE and ETE/P186G, a mutant predicted to possess a functional oxyanion hole, thus downplaying the influence of the flip on the activity. Finally, we observed the formation of ETE homodimers in solution and the predicted homodimeric structure revealed the participation of a characteristic nonconserved loop in the interface and the partial occlusion of the protein active site, suggesting that monomerization is required for enzymatic activity.

Enantioselective Heck-Matsuda Reactions: From Curiosity to a Game-Changing Methodology.

The enantioselective palladium-catalyzed Heck arylation of olefins using arenediazonium salts is one of the last features in the evolution of a synthetic method known as the Heck-Matsuda reaction. This personal account highlights the development of the enantioselective Heck-Matsuda reaction in its initial stages, the challenges faced along the way, and the interesting findings that opened new synthetic opportunities, mainly from our laboratory, featuring the Heck-Matsuda reaction as a central player in the synthesis of bioactive and functional molecules.

Catalytic Enantioselective Transformations Involving C-H Bond Cleavage by Transition-Metal Complexes.

The development of new methods for the direct functionalization of unactivated C-H bonds is ushering in a paradigm shift in the field of retrosynthetic analysis. In particular, the catalytic enantioselective functionalization of C-H bonds represents a highly atom- and step-economic approach toward the generation of structural complexity. However, as a result of their ubiquity and low reactivity, controlling both the chemo- and stereoselectivity of such processes constitutes a significant challenge. Herein we comprehensively review all asymmetric transition-metal-catalyzed methodologies that are believed to proceed via an inner-sphere-type mechanism, with an emphasis on the nature of stereochemistry generation. Our analysis serves to document the considerable and rapid progress within in the field, while also highlighting limitations of current methods.

Chiral 1,3,2-Diazaphospholenes as Catalytic Molecular Hydrides for Enantioselective Conjugate Reductions.

Secondary 1,3,2-diazaphospholenes have a polarized P-H bond and are emerging as molecular hydrides. Herein, a class of chiral, conformationally restricted methoxy-1,3,2-diazaphospholene catalysts is reported. We demonstrate their catalytic potential in asymmetric 1,4-reductions of α,ß-unsaturated carbonyl derivatives, including enones, acyl pyrroles, and amides, which proceeded in enantioselectivities of up to 95.5:4.5 e.r.

Quaternary Stereogenic Centers through Enantioselective Heck Arylation of Acyclic Olefins with Aryldiazonium Salts: Application in a Concise Synthesis of (R)-Verapamil.

We describe herein a highly regio- and enantioselective Pd-catalyzed Heck arylation of unactivated trisubstituted acyclic olefins to provide all-carbon quaternary stereogenic centers. Chiral N,N ligands of the pyrimidine- and pyrazino-oxazoline class were developed for that purpose, providing the desired products in good to high yields with enantiomeric ratios up to >99:1. Both linear and branched substituents on the olefins were well-tolerated. The potential of this new method is demonstrated by the straightforward synthesis of several O-methyl lactols and lactones containing quaternary stereocenters, together with a concise enantioselective total synthesis of the calcium channel blocker verapamil.

Stereoselective synthesis of aryl cyclopentene scaffolds by Heck-Matsuda desymmetrization of 3-cyclopentenol.

A new enantioselective Heck-Matsuda desymmetrization reaction was accomplished by using 3-cyclopentenol to produce chiral five-membered 4-aryl cyclopentenol scaffolds in good yields and high ee's, together with some 3-aryl-cyclopentanones as minor products. Mechanistically, the hydroxyl group of 3-cyclopentenol acts as a directing group and is responsible for the cis- arrangement in the formation of the 4-aryl-cyclopentenols.

A facile approach to TiO2 colloidal spheres decorated with Au nanoparticles displaying well-defined sizes and uniform dispersion.

This paper describes a straightforward approach for the synthesis of hybrid materials composed of titanium dioxide (TiO(2)) colloidal spheres decorated with gold nanoparticles (Au NPs). In the reported method, monodisperse TiO(2) colloidal spheres (∼220 nm in diameter) could be directly employed as templates for the nucleation and growth of Au NPs over their surface using AuCl(4)(-)(aq) as the Au precursor, ascorbic acid as the reducing agent, PVP as the stabilizer, and water as the solvent. The Au NPs presented a uniform distribution over the TiO(2) surface. Interestingly, the size of the Au NPs could be controlled by performing sequential reduction steps with AuCl(4)(-)(aq). This method could also be adapted for the production of TiO(2) colloidal spheres decorated with other metal NPs including silver (Ag), palladium (Pd), and platinum (Pt). The catalytic activities of the TiO(2)-Au materials as a function of composition and NPs size were investigated toward the reduction of 4-nitrophenol to 4-aminophenol under ambient conditions. An increase of up to 10.3-fold was observed for TiO(2)-Au relative to TiO(2). A surface-enhanced Raman scattering application for TiO(2)-Au was also demonstrated employing 4-mercaptopyridine as the probe molecule. The results presented herein indicate that our approach may serve as a platform for the synthesis of hybrid materials containing TiO(2) and metal NPs displaying well-defined morphologies, compositions, and sizes. This can have important implications for the design of TiO(2)-based materials with improved performances for photocatalysis and photovoltaic applications.

Investigating the influence of the interface in thiol-functionalized silver-gold nanoshells over lipase activity.

We employed thiol-funcionalized AgAu nanoshells (AgAu NSs) as supports for the covalent attachment of lipases (BCL, Burkholderia cepacia lipase; PPL, pancreatic porcine lipase). Specifically, we were interested in investigating the effect of the nature/size of the spacer in AgAu NSs-functionalized organic thiols over the covalent attachment of lipases. The catalytic performance of AgAu-lipase systems was measured in the kinetic resolution of (R,S)-1-(phenyl)ethanol via a transesterification reaction. In comparison to free BCL, the lipase attached to AgAu NSs using a small spacer such as cysteamine or mercaptoacetic acid, with the largest spacer mercaptoundecanoic acid, had the fastest conversion rate. The recycling potential for BCL was investigated. After three reaction cycles, the enzyme activity was kept at around 90% of the initial value. The results described herein show that the size of the spacer plays an important role in optimizing lipase activities in metallic nanoshells as solid supports.

Intermolecular enantioselective Heck-Matsuda arylations of acyclic olefins: application to the synthesis of ß-aryl-γ-lactones and ß-aryl aldehydes.

We describe herein a synthetically useful method for the enantioselective intermolecular Heck-Matsuda arylation of acyclic allylic alcohols. Aryldiazonium tetrafluoroborates were applied as arylating agents in the presence of Pd(TFA)2 and a chiral, commercially available, bisoxazoline ligand. The methodology is straightforward, robust, scalable up to a few grams, and of broad scope allowing the synthesis of a range of ß-aryl-carbonyl compounds in good to high enantioselectivities and yields. This new enantioselective Heck-Matsuda arylation allowed the synthesis of ß-aryl-γ-lactones and ß-aryl aldehydes, which play a vital role as key intermediates in the synthesis of the biologically active compounds, such as (R)-baclofen, (R)-rolipram, (S)-curcumene, (S)-dehydrocurcumene, and (S)-tumerone.

Size-controlled synthesis of silver micro/nanowires as enabled by HCL oxidative etching.

The polyol method has been widely employed for the synthesis of uniform silver nanowires (Ag NWs) in high yields. In this article, we describe the utilization of HCl oxidative etching as an effective strategy to control the width of Ag NWs produced by the polyol approach. More specifically, the width of the produced Ag NWs could be tuned from 65 to 765 nm by varying the HCl concentration in the polyol recipe. Our results indicate that the obtained widths displayed a linear and steady increase according to the HCl concentration employed in the reaction. Although the width was also dependent on other experimental parameters such as the AgNO(3) and polyvinylpirrolidone (PVP) concentrations and temperature, the HCl oxidative etching enabled the controlled synthesis of Ag NWs over the widest range of widths. The size-dependent optical property investigations revealed that the transverse mode surface plasmon resonance peak for the produced Ag NWs red-shifted from 378 to 467 nm as their width increased from 77 to 584 nm. The application of Ag NWs (77 nm) as SERS substrates for the detection of 4-mercaptopyridine was also demonstrated. As the properties of metal nanostructures are strongly dependent upon size, the results reported herein can have important implications for designing the synthesis of uniform Ag NWs in high yields displaying controlled and/or desired dimensions for applications in areas including plasmonics, electronics, and sensing.

Stereoselective arylation of substituted cyclopentenes by substrate-directable Heck-Matsuda reactions: a concise total synthesis of the sphingosine 1-phosphate receptor (S1P(1)) agonist VPC01091.

We describe herein an efficient and diastereoselective substrate-directable Heck-Matsuda reaction with nonactivated five-membered olefins. The carbamate acts as the main directing group in the arylation process allowing the synthesis of several functionalized aryl cyclopentenes in good to excellent diastereoselectivities (>85:15) and in isolated yields ranging from 41 to 90%. No double bond isomerizations were observed in these Heck reactions, and the newly created benzylic centers were preserved in all cases examined. The substrate directable Heck arylation approach was successfully applied in a straightforward total synthesis of the sphingosine 1-phosphate receptor-subtype 1 (S1P(1)) agonist VPC01091 by a concise and practical route involving 5 steps in 40% overall yield.

Improving the Stability and Efficiency of Perovskite Solar Cells by a Bidentate Anilinium Salt.

We report improvement in the perovskite solar cell efficiency and stability after passivation with an organic molecule decorated with two anilinium cations. We compare this salt with its neutral analog and found that the change in the electron density distribution upon protonation and the presence of the halide anion are key to explaining the better passivation ability of the salt. In addition, we show that the counteranion has a significant impact on the performance of the device.

Chemo-, regio- and stereoselective Heck arylation of allylated malonates: mechanistic insights by ESI-MS and synthetic application toward 5-arylmethyl-γ-lactones.

We describe herein a general method for the controlled Heck arylation of allylated malonates. Both electron-rich and electron-poor aryldiazonium salts were readily employed as the aryl-transfer agents in good yields and in high chemo-, regio-, and stereoselectivity without formation of decarboxylated byproducts. Reaction monitoring via ESI-MS was used to support the formation of chelated Pd species through the catalytic cycle. Additionally, some Heck adducts were successfully used in the total synthesis of pharmacologically active γ-lactones.