N-Heterocyclic carbenes (NHCs) are versatile species that figure prominently as catalysts. Despite their widespread use in organocatalysis, studies of the relationship between the basicity of NHCs and their catalytic ability are limited. Herein we review work on both the examination of NHC basicity as well as its impact on organocatalysis. The review is divided into three main parts: an overview of NHC basicity studies, both in solution and in the gas phase; the role of basicity in Umpolung-type catalysis; and the relationship between NHC basicity and its growing role as a Brønsted base catalyst. This review is not an exhaustive catalog of all NHC catalysis, but rather focuses on work that specifically examines and discusses the effect of NHC basicity on catalyst function.

Intra-abdominal candidiasis (IAC) is one of the most common yet underappreciated form of invasive candidiasis. IAC is difficult to treat, and therapeutic failure and drug resistant breakthrough infections are common in some institutions despite the use of echinocandins as first line agents. Fosmanogepix (FMGX, formerly APX001) is a first-in-class antifungal prodrug that can be administered both intravenously and orally. FMGX is currently in Phase 2 clinical development for the treatment of life-threatening invasive fungal infections. To explore the pharmacological property and therapeutic potential of FMGX for IAC, we evaluated both drug penetration and efficacy of the active moiety manogepix (MGX, formerly APX001A) in infected liver tissues in a clinically relevant IAC mouse model due to C. albicans. Matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) and laser capture microdissection (LCM)-directed absolute drug quantitation were employed to evaluate drug penetration into liver abscess lesions both spatially and quantitatively. The partitioning of MGX into lesions occurred slowly after a single dose; however robust accumulation in the lesion was achieved after 3 days of repeated dosing. Associated with this drug penetration pattern, reduction in fungal burden and clearance in the liver were observed in mice receiving the multi-day FMGX regimen. In comparison, administration of micafungin resulted in marginal reduction in fungal burden at the end of 4 days of treatment. These results suggest that FMGX is a promising candidate for the treatment of IAC.

The capture and storage of carbon dioxide are pressing environmental concerns. Nucleophilic capture by anions in ionic liquids, such as imidazolates, is a promising strategy. Herein, the gas-phase acidity of a series of imidazoles is examined both experimentally and computationally. The intrinsic acidity of these imidazoles has not heretofore been measured; these experimental data provide a benchmark for the computational values. The relationship between imidazole acidity and carbon dioxide capture is explored computationally, both in the gas phase and in ionic liquid. The improved understanding of imidazolate properties provided herein is important for the design and development of improved systems for carbon dioxide capture.

Suboptimal antibiotic dosing has been identified as one of the key drivers in the development of multidrug‐resistant (MDR) bacteria that have become a global health concern. Aminoglycosides and vancomycin are broad‐spectrum antibiotics used to treat critically ill patients infected by a variety of MDR bacterial species. Resistance to these antibiotics is becoming more prevalent. In order to design proper antibiotic regimens that maximize efficacy and minimize the development of resistance, it is pivotal to obtain the in situ pharmacokinetic–pharmacodynamic profiles at the sites of infection. Mass spectrometry imaging (MSI) is the ideal technique to achieve this. Aminoglycosides, due to their structure, suffer from poor ionization efficiency. Additionally, ion suppression effects by endogenous molecules greatly inhibit the detection of aminoglycosides and vancomycin at therapeutic levels. In the current study, an optimized method was developed that enabled the detection of these antibiotics by MSI. Tissue spotting experiments demonstrated a 5‐, 15‐, 35‐, and 54‐fold increase in detection sensitivity in the washed samples for kanamycin, amikacin, streptomycin, and vancomycin, respectively. Tissue mimetic models were utilized to optimize the washing time and matrix additive concentration. These studies determined the improved limit of detection was 40 to 5 μg/g of tissue for vancomycin and streptomycin, and 40 to 10 μg/g of tissue for kanamycin and amikacin. The optimized protocol was applied to lung sections from mice dosed with therapeutic levels of kanamycin and vancomycin. The washing protocol enabled the first drug distribution investigations of aminoglycosides and vancomycin by MSI, paving the way for site‐of‐disease antibiotic penetration studies.