Cephem-Pyrazinoic Acid Conjugates: Circumventing Resistance in Mycobacterium tuberculosis

Tuberculosis (TB) is a leading source of infectious disease mortality globally. Antibiotic-resistant strains comprise an estimated 10 % of new TB cases and present an urgent need for novel therapeutics. β-lactam antibiotics have traditionally been ineffective against M. tuberculosis (Mtb), the causative agent of TB, due to the organism's inherent expression of β-lactamases that destroy the electrophilic β-lactam warhead. We have developed novel β-lactam conjugates, which exploit this inherent β-lactamase activity to achieve selective release of pyrazinoic acid (POA), the active form of a first-line TB drug. These conjugates are selectively active against M. tuberculosis and related mycobacteria, and activity is retained or even potentiated in multiple resistant strains and models. Preliminary mechanistic investigations suggest that both the POA “warhead” as well as the β-lactam “promoiety” contribute to the observed activity, demonstrating a codrug strategy with important implications for future TB therapy.     

On-Surface Metathesis of an Ionic Liquid on Ag(111)

We investigated the adsorption, surface enrichment, ion exchange, and on-surface metathesis of ultrathin mixed IL films on Ag(111). We stepwise deposited 0.5 ML of the protic IL diethylmethylammonium trifluoromethanesulfonate ([dema][TfO]) and 1.0 ML of the aprotic IL 1-methyl-3-octylimidazolium hexafluorophosphate ([C₈C₁Im][PF₆]) at around 90 K. Thereafter, the resulting layered frozen film was heated to 550 K, and the thermally induced phenomena were monitored in situ by angle-resolved X-ray photoelectron spectroscopy. Between 135 and 200 K, [TfO]⁻ anions at the Ag(111) surface are exchanged by [PF₆]⁻ anions and enriched together with [C₈C₁Im]⁺ cations at the IL/vacuum interface. Upon further heating, [dema][PF₆] and [OMIm][PF₆] desorb selectively at ∼235 and ∼380 K, respectively. Hereby, a wetting layer of pure [C₈C₁Im][TfO] is formed by on-surface metathesis at the IL/metal interface, which completely desorbs at ∼480 K. For comparison, ion enrichment at the vacuum/IL interface was also studied in macroscopic IL mixtures, where no influence of the solid support is expected.     

Flow Synthesis of Plasmonic Gold Nanoshells via a Microreactor

Gold nanoshells with tunable surface plasmon resonances are a promising material for optical and biomedical applications. They are produced through seed‐mediated growth, in which gold nanoparticles (AuNPs) are seeded on the core particle surface followed by growth of the gold seeds into a shell. However, synthetic gold nanoshell production is typically a multistep, time‐consuming batch‐type process, and a simple and scalable process remains a challenge. In the present study, a continuous flow process for the seed‐mediated growth of silica–gold nanoshells is established by exploiting the excellent mixing performance of a microreactor. In the AuNP‐seeding step, the reduction of gold ions in the presence of core particles in the microreactor enables the one‐step flow synthesis of gold‐decorated silica particles through heterogeneous nucleation. Flow shell growth is also realized using the microreactor by selecting an appropriate reducing agent. Because self‐nucleation in the bulk solution phase is suppressed in the microreactor system, no washing is needed after each step, thus enabling the connection of the microreactors for the seeding and shell growth steps into a sequential flow process to synthesize gold nanoshells. The established system is simple and robust, thus making it a promising technology for producing gold nanoshells in an industrial setting.     

Dealloying of Mesoporous PtCu Alloy Film for the Synthesis of Mesoporous Pt Films with High Electrocatalytic Activity

Mesoporous Pt film with highly electrocatalytic activity is successfully synthesized by dealloying of mesoporous PtCu alloy film prepared through electrochemical micelle assembly. The resulting mesoporous electrode exhibits high current density and superior stability toward the methanol oxidation reaction.     

Easy and General Synthesis of Large‐Sized Mesoporous Rare‐Earth Oxide Thin Films by ′Micelle Assembly′

Large‐sized (ca. 40 nm) mesoporous Er₂O₃ thin films are synthesized by using a triblock copolymer poly(styrene‐b‐2‐vinyl pyridine‐b‐ethylene oxide) (PS‐b‐P2VP‐b‐PEO) as a pore directing agent. Each block makes different contributions and the molar ratio of PVP/Er³⁺ is crucial to guide the resultant mesoporous structure. An easy and general method is proposed and used to prepare a series of mesoporous rare‐earth oxide (Sm₂O₃, Dy₂O₃, Tb₂O₃, Ho₂O₃, Yb₂O₃, and Lu₂O₃) thin films with potential uses in electronics and optical devices.     

Unexpected effect of catalyst concentration on photochemical CO2 reduction by trans(Cl)–Ru(bpy)(CO)2Cl2: new mechanistic insight into the CO/HCOO– selectivity

Photochemical CO₂ reduction catalysed by trans(Cl)–Ru(bpy)(CO)₂Cl₂ (bpy = 2,2′-bipyridine) efficiently produces carbon monoxide (CO) and formate (HCOO^–) in N,N-dimethylacetamide (DMA)/water containing [Ru(bpy)₃]²⁺ as a photosensitizer and 1-benzyl-1,4-dihydronicotinamide (BNAH) as an electron donor. We have unexpectedly found catalyst concentration dependence of the product ratio (CO/HCOO^–) in the photochemical CO₂ reduction: the ratio of CO/HCOO^– decreases with increasing catalyst concentration. The result has led us to propose a new mechanism in which HCOO^– is selectively produced by the formation of a Ru(i)–Ru(i) dimer as the catalyst intermediate. This reaction mechanism predicts that the Ru–Ru bond dissociates in the reaction of the dimer with CO₂, and that the insufficient electron supply to the catalyst results in the dominant formation of HCOO^–. The proposed mechanism is supported by the result that the time-course profiles of CO and HCOO^– in the photochemical CO₂ reduction catalysed by [Ru(bpy)(CO)₂Cl]₂ (0.05 mM) are very similar to those of the reduction catalysed by trans(Cl)–Ru(bpy)(CO)₂Cl₂ (0.10 mM), and that HCOO^– formation becomes dominant under low-intensity light. The kinetic analyses based on the proposed mechanism could excellently reproduce the unusual catalyst concentration effect on the product ratio. The catalyst concentration effect observed in the photochemical CO₂ reduction using [Ru(4dmbpy)₃]²⁺ (4dmbpy = 4,4′-dimethyl-2,2′-bipyridine) instead of [Ru(bpy)₃]²⁺ as the photosensitizer is also explained with the kinetic analyses, reflecting the smaller quenching rate constant of excited [Ru(4dmbpy)₃]²⁺ by BNAH than that of excited [Ru(bpy)₃]²⁺. We have further synthesized trans(Cl)–Ru(6Mes-bpy)(CO)₂Cl₂ (6Mes-bpy = 6,6′-dimesityl-2,2′-bipyridine), which bears bulky substituents at the 6,6′-positions in the 2,2′-bipyridyl ligand, so that the ruthenium complex cannot form the dimer due to the steric hindrance. We have found that this ruthenium complex selectively produces CO, which strongly supports the catalytic mechanism proposed in this work.     

Laser-induced pinpoint hydrogen evolution from benzene and water using metal free single-walled carbon nanotubes with high quantum yields

Metal-free photocatalytic hydrogen evolution occurred efficiently in benzene containing single-walled carbon nanotubes under laser irradiation at 532 nm with an extremely high turnover number of 2 000 000 and a high quantum yield of 130%. The rate of hydrogen evolution increased with increasing laser intensity to exhibit a fourth power dependence, suggesting that hydrogen was evolved via four-photon processes in which the coupling of two radical anions derived from benzene is the rate-determining step and the benzene radical anion is produced by electron transfer from benzene to the doubly excited state of single-walled carbon nanotubes, which requires two photons. Polymerisation of benzene was induced by the photogenerated C₆H₆˙^–, accompanied by hydrogen evolution, resulting in a leverage effect to increase the quantum yield of hydrogen evolution to well over the 25% expected for the four-photon process. Laser-induced hydrogen evolution also occurred in water containing single-walled carbon nanotubes. In contrast to the case of benzene, water was not oxidized but hydrogen evolution from water was accompanied by the multi-oxidation of single-walled carbon nanotubes. The yield of hydrogen based on one mole of single-walled carbon nanotubes with 1.4 nm diameter and 1–5 mm length was determined to be 2 700 000%, when oxidations of single-walled carbon nanotubes occurred to produce the polyhydroxylated product.