Dimethylarginine dimethylaminohydrolase (DDAH) is a highly conserved hydrolytic enzyme found in numerous species, including bacteria, rodents, and humans. In humans, the DDAH-1 isoform is known to metabolize endogenous asymmetric dimethylarginine (ADMA) and monomethyl arginine (l-NMMA), with ADMA proposed to be a putative marker of cardiovascular disease. Current literature reports identify the DDAH family of enzymes as a potential therapeutic target in the regulation of nitric oxide (NO) production, mediated via its biochemical interaction with the nitric oxide synthase (NOS) family of enzymes. Increased DDAH expression and NO production have been linked to multiple pathological conditions, specifically, cancer, neurodegenerative disorders, and septic shock. As such, the discovery, chemical synthesis, and development of DDAH inhibitors as potential drug candidates represent a growing field of interest. This review article summarizes the current knowledge on DDAH inhibition and the derived pharmacokinetic parameters of the main DDAH inhibitors reported in the literature. Furthermore, current methods of development and chemical synthetic pathways are discussed.

The remarkable properties of deuterium have led to many exciting and favourable results in enhancing material properties, for applications in the physical, medical, and biological sciences. Deuterated isotopologues of avobenzone, a sunscreen active ingredient, were synthesised to examine for any changes to the equilibrium between the diketone and enol isomers, as well as their UV photostability and photoprotective properties. Prior to UV irradiation, deuteration of the diketone methylene/enol moiety (i.e. avobenzone-d₂) led to an increase in the % diketone compared to non-deuterated, determined by ¹H NMR experiments in CDCl₃ and C₆D₁₂. This can be rationalised from two angles; mechanistically by a deuterium kinetic isotope effect for the CH vs. CD abstraction step during tautomerisation from the diketone to the enol, and a weaker chelating hydrogen bond for the enol when deuterated allowing increased equilibration to the diketone. Avobenzone-d₂ was further examined by solid state ¹³C NMR. The higher % diketone for avobenzone-d₂ was postulated to favour increased photodegradation by a non-reversible pathway. This was investigated by UV irradiation of the avobenzone isotopologues in C₆D₁₂, both in real time in situ within the NMR by fibre optic cable as well as ex situ using sunlight. An increase in the relative amount of photoproducts for avobenzone-d₂ compared to non-deuterated was observed by ¹H NMR upon UV irradiation ex situ. Overall, the study demonstrates that deuteration can be applied to alter complex equilibria, and has potential to be manifested as changes to the properties and behaviour of materials.

A capillary electrophoresis coupled to tandem mass spectrometry (CE–MS/MS) has been used to make a qualitative determination of hercynine—the main precursor of l-ergothioneine biosynthesis—in some key human biological specimens, such as urine, whole blood, plasma, and saliva. From semiquantitative analysis results, the highest concentrations of hercynine were detected in saliva and whole blood, whereas much lower concentrations were measured in urine and plasma. Whole blood was the biological matrix with the highest concentration of l-ergothioneine followed by plasma, saliva, and urine. The antioxidant effects attributed to l-ergothioneine, along with its peculiar antioxidant mechanism, offer a possible explanation for the presence of the hercynine, as well as its concentration, in the considered biological matrices.

The effect of the degree of conformational rigidity and/or flexibility on preorganisation in artificial molecular receptors continues to be actively explored by supramolecular chemists. This work describes a bis-porphyrin architecture, linked via a rigid polycyclic backbone, in which a sterically bulky 2,3,5,6-tetramethylphenyl diimide core restricts rotation to afford two non-interconvertible tweezer conformations; syn- and anti-. After separation, the host–guest chemistry of each conformation was studied independently. The difference in host geometry allows only the syn-conformation to form a strong 1 : 1 bis-porphyrin complex with the diamino ligand 1,4-diazabicyclo[2.2.2]octane (DABCO) (K₁₁ = 1.25 × 10⁸ M⁻¹), with the anti-conformation adopting a 2 : 2 sandwich complex with DABCO (K₂₂ = 5.57 × 10¹⁷ M⁻³).