Reaction methods for selective C–H amination are finding ever-increasing utility for the preparation of nitrogen-derived fine chemicals. This brief account highlights the remarkable versatility of ...dirhodium-based catalysts for promoting oxidation of aliphatic C–H centers in both intra- and intermolecular reaction processes.
In 2007, human papillomavirus (HPV) type 16 was finally recognized as a risk factor, besides smoking and alcohol, for oropharyngeal squamous cell carcinoma (OPSCC), including tonsillar squamous cell ...carcinoma (TSCC), by the International Agency for Research against Cancer. Just before, in 2006, the Food and Drug Administration had approved Gardasil, the first vaccine against HPV16, 18, 6 and 11, for preventive vaccination women against cervical cancer. Concurrently, some Western countries, where smoking was decreasing, disclosed an epidemic increase in the incidence of OPSCC, especially of TSCC and base of tongue cancer (BOTSCC), together accounting for 80–90% of all OPSCCs, and mainly affecting men. The epidemic was later revealed to be due to a rise in HPV‐positive cases, and scientists in the field suggested HPV vaccination also of boys. Globally, there are roughly 96 000 incident OPSCC cases/year of which 20–24% are caused by HPV, thereby accounting for around 22 000 OPSCC cases annually. Of these cases, 80–90% are due to HPV16 infection and would be prevented with the presently registered HPV vaccines. In Western countries, such as Sweden (with almost 400 TSCC and BOTSCC cases per year) and the United States, HPV prevalence in OPSCC is higher and around 70%. HPV vaccination of girls has been initiated in many countries, and the vaccines have been efficient and their side effects limited. HPV vaccination of boys has, however, been the exception, but should definitely not be delayed any further. It would benefit both girls and boys directly, and result in better and more robust herd immunity. Today, we have the possibility to eliminate several high‐risk HPV types in the younger generations and avoid more than 600 000 cancer cases annually worldwide, and this possibility should be embraced by offering global pan‐gender HPV vaccination.
For more than a century, chemists have endeavored to discover and develop reaction processes that enable the selective oxidation of hydrocarbons. In the 1970s, Abramovitch and Yamada described the ...synthesis and electrophilic reactivity of sulfonyliminoiodinanes (RSO2NIPh), demonstrating the utility of this new class of reagents to function as nitrene equivalents. Subsequent investigations by Breslow, Mansuy, and Müller would show such oxidants to be competent for alkene and saturated hydrocarbon functionalization when combined with transition metal salts or metal complexes, namely those of Mn, Fe, and Rh. Here, we trace our own studies to develop N-atom transfer technologies for C–H and π-bond oxidation. This Account discusses advances in both intra- and intermolecular amination processes mediated by dirhodium and diruthenium complexes, as well as the mechanistic foundations of catalyst reactivity and arrest. Explicit reference is given to questions that remain unanswered and to problem areas that are rich for discovery. A fundamental advance in amination technology has been the recognition that iminoiodinane oxidants can be generated in situ in the presence of a metal catalyst that elicits subsequent N-atom transfer. Under these conditions, both dirhodium and diruthenium lantern complexes function as competent catalysts for C–H bond oxidation with a range of nitrogen sources (e.g., carbamates, sulfamates, sulfamides, etc.), many of which will not form isolable iminoiodinane equivalents. Practical synthetic methods and applications thereof have evolved in parallel with inquiries into the operative reaction mechanism(s). For the intramolecular dirhodium-catalyzed process, the body of experimental and computational data is consistent with a concerted asynchronous C–H insertion pathway, analogous to the consensus mechanism for Rh-carbene transfer. Other studies reveal that the bridging tetracarboxylate ligand groups, which shroud the dirhodium core, are labile to exchange under standard reaction conditions. This information has led to the generation of chelating dicarboxylate dinuclear rhodium complexes, exemplified by Rh2(esp)2. The performance of this catalyst system is unmatched by other dirhodium complexes in both intra- and intermolecular C–H amination reactions. Tetra-bridged, mixed-valent diruthenium complexes function as effective promoters of sulfamate ester oxidative cyclization. These catalysts can be crafted with ligand sets other than carboxylates and are more resistant to oxidation than their dirhodium counterparts. A range of experimental and computational mechanistic data amassed with the tetra-2-oxypyridinate diruthenium chloride complex, Ru2(hp)4Cl, has established the insertion event as a stepwise pathway involving a discrete radical intermediate. These data contrast dirhodium-catalyzed C–H amination and offer a cogent model for understanding the divergent chemoselectivity trends observed between the two catalyst types. This work constitutes an important step toward the ultimate goal of achieving predictable, reagent-level control over product selectivity.
Background
Persistent infection with high‐risk human papillomavirus can lead to cervical dysplasia and cancer. Recent studies have suggested associations between the composition of the vaginal ...microbiota, infection with human papillomavirus (HPV) and progression to cervical dysplasia and cancer.
Objective
To assess how specific cervico‐vaginal microbiota compositions are associated with HPV infection, cervical dysplasia and cancer, we conducted a systematic review and network meta‐analysis (registered in PROSPERO: CRD42018112862).
Search strategy
PubMed, Web of science, Embase and Cochrane database.
Selection criteria
All original studies describing at least two community state types of bacteria (CST), based on molecular techniques enabling identification of bacteria, and reporting the association with HPV infection, cervical dysplasia and/or cervical cancer.
Data collection and analysis
For the meta‐analysis, a network map was constructed to provide an overview of the network relationships and to assess how many studies provided direct evidence for the different vaginal microbiota compositions and HPV, cervical dysplasia or cancer. Thereafter, the consistency of the model was assessed, and forest plots were constructed to pool and summarise the available evidence, presenting odds ratios and 95% confidence intervals.
Main results
Vaginal microbiota dominated by non‐Lactobacilli species or Lactobacillus iners were associated with three to five times higher odds of any prevalent HPV and two to three times higher for high‐risk HPV and dysplasia/cervical cancer compared with Lactobacillus crispatus.
Conclusions
These findings suggest an association between certain bacterial community types of the vaginal microbiota and HPV infection and HPV‐related disease. This may be useful for guiding treatment options or serve as biomarkers for HPV‐related disease.
Tweetable
This network meta‐analysis suggests an association between different vaginal bacterial community types and the risk of HPV.
Tweetable
This network meta‐analysis suggests an association between different vaginal bacterial community types and the risk of HPV.
C–H insertion: A method for intermolecular amination of tertiary CH bonds is described that uses limiting amounts of substrate and a convenient phenol‐derived nitrogen source. Structure‐selectivity ...and mechanistic studies suggest that steric interaction between the substrate and active oxidant is the principal determinant of product selectivity.
Error correction is important in classical and quantum computation. Decoherence caused by the inevitable interaction of quantum bits with their environment leads to dephasing or even relaxation. ...Correction of the concomitant errors is therefore a fundamental requirement for scalable quantum computation. Although algorithms for error correction have been known for some time, experimental realizations are scarce. Here we show quantum error correction in a heterogeneous, solid-state spin system. We demonstrate that joint initialization, projective readout and fast local and non-local gate operations can all be achieved in diamond spin systems, even under ambient conditions. High-fidelity initialization of a whole spin register (99 per cent) and single-shot readout of multiple individual nuclear spins are achieved by using the ancillary electron spin of a nitrogen-vacancy defect. Implementation of a novel non-local gate generic to our electron-nuclear quantum register allows the preparation of entangled states of three nuclear spins, with fidelities exceeding 85 per cent. With these techniques, we demonstrate three-qubit phase-flip error correction. Using optimal control, all of the above operations achieve fidelities approaching those needed for fault-tolerant quantum operation, thus paving the way to large-scale quantum computation. Besides their use with diamond spin systems, our techniques can be used to improve scaling of quantum networks relying on phosphorus in silicon, quantum dots, silicon carbide or rare-earth ions in solids.
The steroidal neurotoxin (-)-batrachotoxin functions as a potent agonist of voltagegated sodium ion channels (Navs). Here we report concise asymmetric syntheses of the natural (-) and non-natural (+) ...antipodes of batrachotoxin, as well both enantiomers of a C-20 benzoate-modified derivative. Electrophysiological characterization of these molecules against Nav subtypes establishes the non-natural toxin enantiomer as a reversible antagonist of channel function, markedly different in activity from (-)-batrachotoxin. Protein mutagenesis experiments implicate a shared binding side for the enantiomers in the inner pore cavity of Nav. These findings motivate and enable subsequent studies aimed at revealing how small molecules that target the channel inner pore modulate Nav dynamics.
A general and operationally convenient method for intermolecular amination of C(sp3)−H bonds is described. This technology allows for efficient functionalization of complex molecules, including ...numerous pharmaceutical targets. The combination of pivalonitrile as a solvent, Al2O3 as an additive, and phenyl sulfamate as a nitrogen source affords differential reaction performance and substrate scope. Mechanistic data strongly implicate a pathway for catalyst decomposition that initiates with solvent oxidation, thus providing rationale for the marked influence of pivalonitrile on this reaction process.
Introducing N: A general and operationally convenient method for intermolecular amination of C(sp3)−H bonds allows for efficient functionalization of complex molecules, including numerous pharmaceutical targets. The combination of pivalonitrile as a solvent, Al2O3 as an additive, and phenyl sulfamate as a nitrogen source affords differential reaction performance and substrate scope.
Highlights • Developmental disruptions of serotonin signaling involved in autism. • Hyperserotonemia provokes a loss of serotonin terminals. • Deficiency of the serotonergic system induces mis-wiring ...of neural network.
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