Susceptibility to Oral Antiseptics and Virulence Factors Ex Vivo Associated with Candida spp. Isolated from Dental Prostheses

Abstract

Purpose

To isolate Candida spp. from dental prosthesis users' saliva and to evaluate the isolates for the presence of several virulence factors. This research also aimed to investigate the antifungal activity of 3 commercial mouthwashes/oral antiseptic formulations containing 0.12% chlorhexidine, 0.07% cetylpyridinium, or 0.075% cetylpyridinium against planktonic and sessile (biofilm mode) yeast cells.

Materials and Methods

Forty‐three Candida yeasts were isolated from 32 of 70 selected patients, and the virulence factors of C. albicans, C. krusei, C. glabrata, C. tropicalis, and C. parapsilosis species were investigated by the polymerase chain reaction (PCR) and proteinase in plates. Minimum inhibitory concentration (MIC), and in vitro biofilm assay evaluated the antifungal activity of antiseptics.

Results

C. albicans, C. krusei, C. glabrata, C. tropicalis, and C. parapsilosis were detected in mono and mixed cultures. Only C. albicans displayed genes related to adhesion and proteinases (ALS2, ALS3, SAP1, and SAP3). The aspartate proteinase activity was found in 60.46% of isolates. The tested antiseptic formulations exhibited a MIC less than 1.25% toward yeasts in the planktonic mode. According to XTT ((2,3‐bis(2‐methoxy‐4‐nitro‐5‐sulfophenyl)‐2H‐tetrazolium‐5‐carboxanilide) assay results, most Candida isolates and all mixed cultures formed biofilms within 24 hours. The evaluated antiseptic formulations were also active against biofilms.

Conclusion

Most virulence factors investigated here (ALS2, ALS3, SAP1, and SAP3) occurred in the majority of the Candida spp. isolates, especially in C. albicans. The tested mouthwash formulations were effective against all the yeast isolates in both the planktonic and sessile growth modes. Developing alternative therapies that can avoid or control biofilm formation is necessary to prevent oral candidiasis and other Candida spp. infections.

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Synthesis of Bimetallic Copper‐Rich Nanoclusters Encapsulating a Linear Palladium Dihydride Unit

The structurally precise Cu‐rich hydride nanoclusters [PdCu14H2(dtc/dtp)6(C≡CPh)6] (dtc: di‐butyl dithiocarbamate (1); dtp: di‐isopropyl dithiophosphate (2)) were synthesized from the reaction of polyhydrido copper clusters [Cu28H15(S2CNnBu2)12]+ or [Cu20H11{S2P(OiPr)2}9] with phenyl acetylene in the presence of Pd(PPh3)2Cl2. Their structures and compositions were determined by single crystal X‐ray diffraction and the results were supported by ESI‐mass spectrometry. Hydride positions in 1 were confirmed by single crystal neutron diffraction. Each hydride is connected to one Pd(0) and four Cu(I) atoms in slightly distorted trigonal bipyramidal geometry. The anatomies of clusters 1 and 2 are very similar and DFT calculations allow rationalizing the interactions between the encapsulated PdH2 unit and its Cu14 bicapped icosahedral cage. As a result, Pd has the highest coordination number (14) so far recorded.

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Phosphorus‐Modulation‐Triggered Surface Disorder in Titanium Dioxide Nanocrystals Enables Exceptional Sodium‐Storage Performance

Take the strain: A phosphorus modulation of anatase TiO₂ simultaneously triggers a surface phase transition, which gives structural disorder, and interior atomic‐level P‐doping. These two beneficial changes result in a zero‐strain during sodium‐ion insertion/extraction which occurs with only about 0.1 % volume variation and thus enables an exceptional sodium‐storage performance.

Abstract

Structural modulation and surface engineering have remarkable advantages for fast and efficient charge storage. Herein, we present a phosphorus modulation strategy which simultaneously realizes surface structural disorder with interior atomic‐level P‐doping to boost the Na⁺ storage kinetics of TiO₂. It is found that the P‐modulated TiO₂ nanocrystals exhibit a favourable electronic structure, and enhanced structural stability, Na⁺ transfer kinetics, as well as surface electrochemical reactivity, resulting in a genuine zero‐strain characteristic with only approximately 0.1 % volume variation during Na⁺ insertion/extraction, and exceptional Na⁺ storage performance including an ultrahigh rate capability of 210 mAh g⁻¹ at 50 C and a strong long‐term cycling stability without significant capacity decay up to 5000 cycles at 30 C.

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Complex formation of the tetracycline‐binding aptamer investigated by specific cross‐relaxation under DNP

While dynamic nuclear polarization (DNP) under magic‐angle spinning (MAS) is generally a powerful method capable of greatly enhancing the sensitivity of solid‐state NMR, the displacement of nuclear spin polarization far from thermal equilibrium (i.e., hyperpolarization) also gives rise to peculiar spin dynamics. Here, we elucidate how Specific Cross‐Relaxation Enhancement by Active Motions under DNP (SCREAM‐DNP) can be utilized in order to selectively obtain MAS NMR spectra of an RNA aptamer in a tightly bound complex with a methyl‐bearing ligand (tetracycline) due to the effective CH₃‐reorientation at an optimized sample temperature of ~160 K. We demonstrate that SCREAM‐DNP is able to spectrally isolate the complex from non‐bound species within an RNA mixture and perform a competition assay between the aptamer and a mutant with compromised binding affinity. Finally, we discuss variations in molecular structure and methyl dynamics as observed by SCREAM‐DNP between free tetracycline and when bound in a complex with RNA.

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Dearomatization of 3‐Nitroindoles via a Phosphine‐catalyzed Enantioselective [3+2] Annulation Reaction

A dearomatization process of 3‐nitroindoles via a chiral phosphine‐mediated [3+2] annulation reaction has been developed. This method makes use of readily available 3‐nitroindoles as an aromatic feedstock and quickly delivers a wide range of cyclopentaindoline alkaloid scaffolds in a highly enantioselective manner. Notably, this is the first time that phosphine‐triggered cyclization has been utilized in a dearomatization process.

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Efficient access to deuterated and tritiated nucleobase pharmaceuticals and oligonucleotides using hydrogen isotope exchange

A general approach for the nucleobase derivatives hydrogen isotope exchange is described. Catalyzed by ruthenium nanoparticles, using mild reaction conditions and involving D2 or T2 as isotopic sources, this reaction possesses a wide substrate scope and a high solvent tolerability. This novel method facilitates the convenient access to essential diagnostic tools in drug discovery and development: tritiated pharmaceuticals with high specific activities and deuterated oligonucleotides suitable to be used as internal standards for LC‐MS quantification.

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β‐Selective C‐Glycosylation and its Application in the Synthesis of Scleropentaside A

C‐Glycosides are carbohydrates bearing a C−C bond to an aglycon at the anomeric center. Due to their high stability towards chemical and enzymatic hydrolysis, these compounds are widely used as carbohydrate mimics in drug development. Herein, we report a general and exclusively β selective method for the synthesis of a naturally abundant acyl‐C‐glycosidic structural motif found firstly in the Scleropentaside natural product family. A Corey‐Seebach Umpolung reaction as the key step in the synthesis of Scleropentaside A and analogues enables the β selective construction of the anomeric C−C bond starting from unprotected carbohydrates in only four steps. The methodology is highly atom‐ and pot‐efficient avoiding the use of toxic heavy metals.

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Exploiting Boron Coordination: B←N Bond Supports a [2+2] Photodimerization in the Solid State and Generation of a Diboron Bis‐Tweezer for Benzene/Thiophene Separation

B←N coordination supports a [2+2] photodimerization in the solid state. The bond is defined by an orthogonal interaction between stilbazole and a phenylboronic ester to enable a stereocontrolled and rapid photoreaction. The cyclobutane photoproduct affords a novel diboron bis‐tweezer adduct that is used to separate a mixture of benzene and thiophene upon crystallization.

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Single‐cell phenotypic characterization of Staphylococcus aureus with fluorescent triazole urea activity‐based probes

Phenotypically distinct cellular (sub)populations are clinically relevant for virulence and antibiotic resistance of a bacterial pathogen, but functionally different cells are usually indistinguishable from each other. Here, we introduce fluorescent activity‐based probes as chemical tools for single‐cell phenotypic characterization of enzyme activity levels in Staphylococcus aureus. We screened a 1,2,3‐triazole urea library to identify selective inhibitors of fluorophosphonate‐binding serine hydrolases and lipases in S. aureus and synthesized target‐selective activity‐based probes. Molecular imaging and activity‐based protein profiling studies with these probes revealed a dynamic network within this enzyme family involving compensatory regulation of specific family members and exposed single‐cell phenotypic heterogeneity. We propose chemical probe labeling of enzymatic activities as a generalizable method for phenotyping of bacterial cells at the population and single‐cell level.

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Arylation Chemistry for Bioconjugation

Bioconjugation: This article outlines and reviews sulfur, nitrogen, selenium, oxygen, and carbon arylative bioconjugation strategies and their applications to modify peptides, proteins, sugars, and nucleic acids.

Abstract

Bioconjugation chemistry has been used to prepare modified biomolecules with functions beyond what nature intended. Central to these techniques is the development of highly efficient and selective bioconjugation reactions that operate under mild, biomolecule compatible conditions. Methods that form a nucleophile–sp² carbon bond show promise for creating bioconjugates with new modifications, sometimes resulting in molecules with unparalleled functions. Here we outline and review sulfur, nitrogen, selenium, oxygen, and carbon arylative bioconjugation strategies and their applications to modify peptides, proteins, sugars, and nucleic acids

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Multicatalytic Approach to the Hydroaminomethylation of α‐Olefins

Two cats make HAM: Two distinct, mutually compatible catalysts enable the hydroaminomethylation of alkenes at or near atmospheric pressure of syngas and just 80 °C. The hydroformylation step is catalyzed by a rhodium diphosphine complex, and the reductive amination step, which is conducted as a transfer hydrogenation with aqueous, buffered sodium formate as the reducing agent, is catalyzed by a cyclometallated iridium complex.

Abstract

We report an approach to conducting the hydroaminomethylation of diverse α‐olefins with a wide range of alkyl, aryl, and heteroarylamines at relatively low temperatures (70–80 °C) and pressures (1.0–3.4 bar) of synthesis gas. This approach is based on simultaneously using two distinct catalysts that are mutually compatible. The hydroformylation step is catalyzed by a rhodium diphosphine complex, and the reductive amination step, which is conducted as a transfer hydrogenation with aqueous, buffered sodium formate as the reducing agent, is catalyzed by a cyclometallated iridium complex. By adjusting the ratio of CO to H₂, we conducted the reaction at one atmosphere of gas with little change in yield. A diverse array of olefins and amines, including hetreroarylamines that do not react under more conventional conditions with a single catalyst, underwent hydroaminomethylation with this new system, and the pharmaceutical ibutilide was prepared in higher yield and under milder conditions than with a single catalyst.

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Photoredox‐Catalyzed Cyclobutane Synthesis by a Deboronative Radical Addition–Polar Cyclization Cascade

Arylboronate complexes formed from alkylboronic esters and phenyllithium were found to undergo facile single‐electron oxidation to form alkyl radicals. The novel use of these complexes as radical precursors enabled the development of a photoredox‐catalyzed cyclobutane synthesis proceeding through a radical‐polar crossover mechanism.

Abstract

Photoredox‐catalyzed methylcyclobutanations of alkylboronic esters are described. The reactions proceed through single‐electron transfer induced deboronative radical addition to an electron‐deficient alkene followed by single‐electron reduction and polar 4‐exo‐tet cyclization with a pendant alkyl halide. Key to the success of the methodology was the use of easily oxidizable arylboronate complexes. Structurally diverse cyclobutanes are shown to be conveniently prepared from readily available alkylboronic esters and a range of haloalkyl alkenes. The mild reactions display excellent functional group tolerance, and the radical addition‐polar cyclization cascade also enables the synthesis of 3‐, 5‐, 6‐, and 7‐membered rings.

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General Cyclopropane Assembly by Enantioselective Transfer of a Redox‐Active Carbene to Aliphatic Olefins

Going to the source: The asymmetric synthesis of cyclopropanes is currently designed using specific strategies that depend on the materials available and the final functionality of each target. Presented here is a comprehensive approach that engages simple feedstocks, including aliphatic olefins, with a single redox‐active carbene precursor (NHPI‐DA), which acts as a universal source for a chiral C−H unit.

Abstract

Asymmetric cyclopropane synthesis currently requires bespoke strategies, methods, substrates, and reagents, even when targeting similar compounds. This approach slows down discovery and limits available chemical space. Introduced herein is a practical and versatile diazocompound and its performance in the first unified asymmetric synthesis of functionalized cyclopropanes. The redox‐active leaving group in this reagent enhances the reactivity and selectivity of geminal carbene transfer. This effect allowed the asymmetric cyclopropanation of various olefins, including unfunctionalized aliphatic alkenes, that enables the three‐step total synthesis of (−)‐dictyopterene A. This unified synthetic approach delivers high enantioselectivities that are independent of the stereoelectronic properties of the functional groups transferred. Our results demonstrate that orthogonally differentiated diazocompounds are viable and advantageous equivalents of single‐carbon chirons.

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Photoredox‐Catalyzed Site‐Selective α‐C(sp3)−H Alkylation of Primary Amine Derivatives

By choice: Judicious choice in nitrogen protecting group allows the site‐selective functionalization α to a primary amine. Under photoredox catalysis conditions, a variety of alkene acceptors participate, leading to good yields and excellent selectivities. Tf=trifluoromethanesulfonyl.

Abstract

The synthetic utility of tertiary amines to oxidatively generate α‐amino radicals is well established, however, primary amines remain challenging because of competitive side reactions. This report describes the site‐selective α‐functionalization of primary amine derivatives through the generation of α‐amino radical intermediates. Employing visible‐light photoredox catalysis, primary sulfonamides are coupled with electron‐deficient alkenes to efficiently and mildly construct C−C bonds. Interestingly, a divergence between intermolecular hydrogen‐atom transfer (HAT) catalysis and intramolecular [1,5] HAT was observed through precise manipulation of the protecting group. This dichotomy was leveraged to achieve excellent α/δ site‐selectivity.

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DNA‐Decorated, Helically Twisted Nanoribbon: A Scaffold for the Fabrication of One‐Dimensional, Chiral, Plasmonic Nanostructures

Scarlet ribbons: This work reports the amphiphilicity‐driven self‐assembly of DNA–hexaphenylbenzene conjugates into DNA‐decorated, helically twisted nanoribbons, which can act as a universal template for the fabrication of 1D chiral plasmonic nanomaterials.

Abstract

Crafting of chiral plasmonic nanostructures is extremely important and challenging. DNA‐directed organization of nanoparticle on a chiral template is the most appealing strategy for this purpose. Herein, we report a supramolecular approach for the design of DNA‐decorated, helically twisted nanoribbons through the amphiphilicity‐driven self‐assembly of a new class of amphiphiles derived from DNA and hexaphenylbenzene (HPB). The ribbons are self‐assembled in a lamellar fashion through the hydrophobic interactions of HPB. The transfer of molecular chirality of ssDNA into the HPB core results in the bias of one of the chiral propeller conformations for HPB and induces a helical twist into the lamellar packing, and leads to the formation of DNA‐wrapped nanoribbons with M‐helicity. The potential of the ribbon to act as a reversible template for the 1D chiral organization of plasmonic nanomaterials through DNA hybridization is demonstrated.

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2,2′‐Diamino‐6,6′‐diboryl‐1,1′‐binaphthyl: A Versatile Building Block for Temperature‐Dependent Dual Fluorescence and Switchable Circularly Polarized Luminescence

The combination of two donor–π‐acceptor subunits in the 2,2′‐diamino‐6,6′‐diboryl‐1,1′‐binaphthyl scaffold generates a versatile building block for organic fluorophores exhibiting temperature‐dependent dual fluorescence and switchable circularly polarized luminescence.

Abstract

Temperature‐dependent dual fluorescence and switchable circularly polarized luminescence (CPL) are two highly pursued but challenging properties for small organic molecules (SOMs). We herein disclose a triarylborane π‐system based on a 2,2′‐diamino‐6,6′‐diboryl‐1,1′‐binaphthyl scaffold that can serve as a versatile building block for achieving these two properties by simply choosing different amino groups. BNMe₂‐BNaph with less bulky dimethylamino groups displays temperature‐dependent dual fluorescence, and can thus be used as a highly sensitive ratiometric fluorescence thermometer. On the other hand, BNPh₂‐BNaph with bulky diphenylamino groups exhibits intense fluorescence in both solution and in the solid state. A change of solvent from nonpolar cyclohexane to highly polar MeCN not only shifts the CPL position to much longer wavelength but also inverts the CPL sign. In addition, the complexation of BNPh₂‐BNaph with fluoride greatly enhances the CPL intensity.

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Copper‐Catalyzed Enantioselective Construction of Tertiary Propargylic Sulfones

Copper to the rescue: A general method for the synthesis of propargylic sulfones featuring quaternary stereocenters has been developed. The method relies on a copper‐catalyzed sulfonylation of propargylic cyclic carbonates using sodium sulfinates. It provides the first example of such a transition‐metal‐catalyzed enantioselective propargylic substitution reaction with sulfur‐centered nucleophiles and gives access to functionalized tertiary sulfones.

Abstract

Tertiary propargylic sulfones are of significant importance in organic synthesis and medicinal chemistry, but to date no general asymmetric synthesis approach has been developed. We disclose a versatile copper‐catalyzed sulfonylation of propargylic cyclic carbonates using sodium sulfinates that allows the construction of propargylic sulfones featuring elusive quaternary stereocenters. This method provides the first successful example of such an enantioselective propargylic sulfonylation, features high asymmetric induction, wide functional group tolerance, and scalability, and enables attractive product diversification.

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From Supramolecular Species to Self‐Templated Porous Carbon and Metal‐Doped Carbon for Oxygen Reduction Reaction Catalysts

Making mesopores: The supramolecular interactions within cucurbit[6]uril enable a step by step pyrolysis mechanism, which aids the construction of mesopores and heteroatom doping in the resulting carbon material. The iron‐doped mesoporous carbon is highly efficient in the oxygen reduction reaction (ORR).

Abstract

The preparation of carbon materials usually involves the decomposition of precursors and the reorganization of the as‐generated fragments. However, the cleavage of bonds and the simultaneous formation of new bonds at nearly the same positions prevents effective yet precise fabrication. Herein, a supramolecular precursor, cucurbit[6]uril, that contains multiple bonds with distinct bond strengths is proposed to decouple the twin problem of simultaneous bond cleavage and formation, allowing multistage transformations to hierarchical porous carbon and metal‐doped carbon in a single yet effective pyrolysis step without the need of a template or additional purification. As a proof‐of‐concept, the Fe‐doped carbon electrocatalysts realized a Pt/C‐like half‐wave potential of 0.869 V vs. RHE and small Tafel slope of 51.3 mV dec⁻¹ in oxygen reduction reaction.

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Platinum/Nickel Bicarbonate Heterostructures towards Accelerated Alkaline Hydrogen Evolution Reaction

Heterostructured nanomaterials, generally possessing unique physicochemical properties different from the individual components, have great potential in a wide range of applications. New platinum (Pt)/nickel bicarbonate (Ni(HCO3)2) heterostructures herein are designed towards efficient alkaline hydrogen evolution reaction (HER). Notably, the specific and mass activity of Pt in Pt/Ni(HCO3)2 are substantially improved as compared with bare Pt NPs. The Ni(HCO3)2 provides abundant water adsorption/dissociation sites and modulate the electronic structure of Pt, both of which determine the elementary reaction kinetics of alkaline HER. Besides, Ni(HCO3)2 nanoplates offer an ideal platform for the uniform dispersion of Pt NPs, ensuring the maximum exposure of active sites. The results demonstrate that, Ni(HCO3)2 is an effective catalyst promoter for alkaline HER, and engineering heterostructures with triggered synergistic effect is a promising strategy towards innovative electrocatalysts development.

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Atomic resolution insight on Sac7d protein binding to DNA and associated global changes by Molecular Dynamics Simulations

Sac7d is a small thermostable protein that induces large helical deformations in DNA upon association. Starting from multiple initial placements of the unbound Sac7d structure relative to a B‐DNA oligonucleotide molecular dynamics (MD) simulations were employed to directly follow several successful binding events at atomic resolution that resulted in structures in close agreement with the native complex geometry. The final native complex formation occurred rapidly within tenth of nanoseconds and included simultaneous large scale kinking, groove opening, twisting and intercalation in the target DNA. The simulations indicate that the complex formation process involved initial non‐native contacts that helped to reach the final bound state with residues intercalated as the center of the kinked DNA. It was also possible to identify several long‐lived trapped intermediate states of the binding process and to follow sliding processes of Sac7d along the DNA minor groove.

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