The fastest synthetic molecular catalysts for H2 production and oxidation emulate components of the active site of hydrogenases. The critical role of controlled structural dynamics is recognized for ...many enzymes, including hydrogenases, but is largely neglected in designing synthetic catalysts. Our results demonstrate the impact of controlling structural dynamics on H2 production rates for Ni(PPh2NC6H4R2)22+ catalysts (R=n‐hexyl, n‐decyl, n‐tetradecyl, n‐octadecyl, phenyl, or cyclohexyl). The turnover frequencies correlate inversely with the rates of chair–boat ring inversion of the ligand, since this dynamic process governs protonation at either catalytically productive or non‐productive sites. These results demonstrate that the dynamic processes involved in proton delivery can be controlled through modification of the outer coordination sphere, in a manner similar to the role of the protein architecture in many enzymes. As a design parameter, controlling structural dynamics can increase H2 production rates by three orders of magnitude with a minimal increase in overpotential.
Slower dynamics, faster catalysis: Dynamic processes that are key to catalysis can be controlled through remote substituents in the outer coordination sphere, in a manner similar to the role of the protein architecture in enzymes. This approach was used to increase the H2 production rates of nickel catalysts by three orders of magnitude with a minimal increase in overpotential.
A longstanding challenge in molecular electrocatalysis is to design catalysts that break away from the tradeoff between rate and overpotential arising from electronic scaling relationships. Here we ...report an inversion of the rate–overpotential correlation through system-level design of Ni(PR 2NR′ 2)22+ electrocatalysts for the production of H2. The overpotential is lowered by an electron-withdrawing ligand, while the turnover frequency is increased by controlling the catalyst structural dynamics, using both ligand design and solvent viscosity. The cumulative effect of controlling each of these system components is an electrocatalyst with a turnover frequency of 70000 s–1 and an overpotential of 230 mV, corresponding to a 100-fold rate enhancement and a 170 mV reduction in overpotential in comparison to the parent nickel catalyst. Molecular Tafel plot analysis reveals that the new catalysts reported here are substantially more efficient than other leading molecular electrocatalysts for the production of H2.
The intramolecular cyclohexylene-bridged P/B frustrated Lewis pair Mes2PC6H10B(C6F5)2 1b reacts rapidly with NO to give the persistent FLP-NO aminoxyl radical 2b formed by P/B addition to the ...nitrogen atom of NO. This species was fully characterized by X-ray diffraction, EPR and UV/vis spectroscopies, C,H,N elemental analysis, and DFT calculations. The reactive oxygen-centered radical 2b undergoes a H-atom abstraction (HAA) reaction with 1,4-cyclohexadiene to give the diamagnetic FLP-NOH product 3b. FLP-NO 2b reacts with toluene at 70 °C in an HAA/radical capture sequence to give a 1:1 mixture of FLP-NOH 3b and FLP-NOCH2Ph 4b, both characterized by X-ray diffraction. Structurally related FLPs Mes2PCHR1CHR2B(C6F5)2 1c, 1d, and 1e react analogously with NO to give the respective persistent FLP-NO radicals 2c, 2d, and 2e, respectively, which show similar HAA and O-functionalization reactions. The FLP-NOCHMePh 6b derived from 1-bromoethylbenzene undergoes NOC bond cleavage at 120 °C with an activation energy of E a = 35(2) kcal/mol. Species 6b induces the controlled nitroxide-mediated radical polymerization (NMP) of styrene at 130 °C to give polystyrene with a polydispersity index of 1.3. The FLP-NO systems represent a new family of aminoxyl radicals that are easily available by N,N-cycloaddition of C2-bridged intramolecular P/B frustrated Lewis pairs to nitric oxide.
The pandemic spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of Coronavirus Disease 2019 (COVID-19), represents an ongoing international health crisis. A ...key symptom of SARS-CoV-2 infection is the onset of fever, with a hyperthermic temperature range of 38 to 41°C. Fever is an evolutionarily conserved host response to microbial infection that can influence the outcome of viral pathogenicity and regulation of host innate and adaptive immune responses. However, it remains to be determined what effect elevated temperature has on SARS-CoV-2 replication. Utilizing a three-dimensional (3D) air-liquid interface (ALI) model that closely mimics the natural tissue physiology of SARS-CoV-2 infection in the respiratory airway, we identify tissue temperature to play an important role in the regulation of SARS-CoV-2 infection. Respiratory tissue incubated at 40°C remained permissive to SARS-CoV-2 entry but refractory to viral transcription, leading to significantly reduced levels of viral RNA replication and apical shedding of infectious virus. We identify tissue temperature to play an important role in the differential regulation of epithelial host responses to SARS-CoV-2 infection that impact upon multiple pathways, including intracellular immune regulation, without disruption to general transcription or epithelium integrity. We present the first evidence that febrile temperatures associated with COVID-19 inhibit SARS-CoV-2 replication in respiratory epithelia. Our data identify an important role for tissue temperature in the epithelial restriction of SARS-CoV-2 independently of canonical interferon (IFN)-mediated antiviral immune defenses.
The vicinal frustrated Lewis pair (FLP) mes2P–CH2CH2–B(C6F5)2 (3) reacts with phenyl(trimethylsilyl)acetylene by 1,1-carboboration to give the extended C3-bridged FLP 6 featuring a substituted ...vinylborane subunit. The FLP 6 actively cleaves dihydrogen. The FLP 3 also undergoes a 1,1-carboboration reaction with diphenylphosphino(trimethylsilyl)acetylene to give the P/B/P FLP 11 that features a central unsaturated four-membered heterocyclic P/B FLP and a pendant CH2CH2–Pmes2 functional group. Compound 11 reacts with nitric oxide (NO) by oxidation of the pendant Pmes2 unit to the P(O)mes2 phosphine oxide and N,N-addition of the P/B FLP unit to NO to yield the persistent P/B/PO FLPNO aminoxyl radical 14. This reaction is initiated by P(O)mes2 formation and opening of the central Ph2P···B(C6F5)2 linkage triggered by the pendant CH2CH2–P(O)mes2 group.
NO your pairs: The intramolecular frustrated Lewis pair (FLP) Mes2PCH2CH2B(C6F5)2 captures NO to give the novel N‐oxyl radical P/B‐FLP‐NO. (see scheme). Coordination of NO to the FLP incites H‐atom ...ion reactivity with cyclohexene and ethylbenzene to give P/B‐FLP‐NOH and the O‐functionalized P/B‐FLP‐NOR species.
The unsaturated vicinal phosphane/borane frustrated Lewis pairs (P/B FLPs) Ph2PC(p-tolyl)=C(R)B(C6F5)2 (R=C6F5 or CH3) react with tert-butyl isocyanide to give an equilibrium mixture of the starting ...materials, the borane/isonitrile adduct and the P/B addition product to the isonitrile carbon atom. The cooperative 1,1-adducts were exclusively formed upon treatment of these FLPs with n-butyl isocyanide. The saturated vicinal FLP Mes2PCH2CH2B(C6F5)2 reacts analogously with carbon monoxide yielding the respective five-membered zwitterionic carbonyl heterocycle. Similarly cooperative CO addition was observed starting from a norbornane based vicinal P/B FLP. These saturated vicinal P/B FLPs (and several related systems) undergo analogous cooperative 1,1-addition reactions to nitric oxide (NO) to give the corresponding persistent five-membered heterocyclic FLP-NO nitroxide radicals. They were characterized spectroscopically and by X-ray diffraction and shown to undergo typical N-oxyl radical reactions. Some vicinal P/B FLPs also undergo 1,1-addition reactions to mesityl azide. Anomalous Staudinger reactions were observed to take place upon subsequent thermolysis or (in one case) photolysis.
Healthcare-associated infections (HCAIs) are considered adverse outcomes of confinement in a healthcare facility. Biofilm-producing, drug-resistant bacteria have further aggravated the problem with ...HCAIs. This study determined the prevalence, antibiotic susceptibility, and biofilm phenotype of coagulase-negative staphylococci (CoNS) isolated from a hospital environment in Northern Philippines. The identification of CoNS species and the determination of antibiotic susceptibility were done using an automated assay. Biofilm production was detected using tissue culture plate (TCP) and Congo red agar (CRA) methods. Out of 220 surfaces and 26 air samples collected, 103 (41.9%) CoNS strains were isolated, predominated by S. epidermidis with 30.1% prevalence. The medical ward was found to have the highest prevalence of CoNS at 64%. The CoNS isolates exhibited a variable resistance profile; the highest was found against penicillin (97.1%) and oxacillin (54.3%). Isolates manifesting resistance to linezolid and vancomycin were also detected. From the 103 CoNS isolates, 52 (50.5%) biofilm producers were detected using the TCP method, and 39 (37.9%) were detected by the CRA method. Statistically significant difference was found between the biofilm biomass and the slime-producing pattern. This study revealed the prevalence of biofilm-producing, drug-resistant strains of CoNS in a Level 3 hospital in Northern Philippines. This warrants further enhancement of infection prevention and control programs to avert the emergence of more biofilm-producing, drug-resistant bacterial strains that could pose formidable threats to public health.
The Dialectic of Essence offers a systematic new account of Plato’s metaphysics. Allan Silverman argues that the best way to make sense of the metaphysics as a whole is to examine carefully what ...Plato says about ousia (essence) from the Meno through the middle period dialogues, the Phaedo and the Republic, and into several late dialogues including the Parmenides, the Sophist, the Philebus, and the Timaeus. This book focuses on three fundamental facets of the metaphysics: the theory of Forms; the nature of particulars; and Plato’s understanding of the nature of metaphysical inquiry.
Hydroboration of dimesitylnorbornenylphosphane with Piers’ borane HB(C6F5)2 gave the frustrated Lewis pair (FLP) 4 in good yield. It has the −PMes2 Lewis base attached at the 2-endo position and the ...−B(C6F5)2 group 3-exo oriented at the norbornane framework. The vicinal FLP 4 was shown by X-ray diffraction and by spectroscopy to be a rare example of an intramolecular noninteracting pair of a Lewis acid and Lewis base functionality. The FLP 4 rapidly splits dihydrogen heterolytically at ambient temperature to yield the phosphonium/hydrido borate zwitterion 5. It adds to the carbonyl group of benzaldehyde and to carbon dioxide to yield the adducts 6 and 7, respectively. Compounds 5–7 were characterized by X-ray diffraction. Compound 4 adds to the SO function of sulfur dioxide to give a pair of diastereomeric heterocyclic six-membered ring products due to the newly formed sulfur chirality center, annulated with the norbornane skeleton, which were investigated by 31P/11B single and double resonance solid state NMR experiments. Compound 8 was also characterized by X-ray diffraction. The FLP 4 undergoes a clean N,N-addition to nitric oxide (NO) to give a norbornane annulated five-membered heterocyclic persistent FLP-NO aminoxyl radical 12 (characterized, e.g., by X-ray diffraction and EPR spectroscopy). Additionally, the FLP radical was characterized by 1H solid state NMR spectroscopy. The radical 12 undergoes a H-atom abstraction reaction with 1,4-cyclohexadiene to yield the respective diamagnetic FLP-NOH product 13, which was also characterized by X-ray diffraction and solid state NMR spectroscopy.
PDF
