N,N-Dimethylbenzylamine, alkyl and aryl imines derived from benzaldehyde, and 2-phenyl-4,4-dimethyloxazoline all undergo cyclometallation with [IrCl₂Cp*]₂ (Cp* = η-C₅Me₅) when treated with NaOAc in dichloromethane at room temperature. The imines are also cyclometallated by [RhCl₂Cp*]₂ under the same conditions whilst only N-alkyl imines are cyclometallated by [RuCl₂(p-cymene)]₂. The role of acetate in the cyclometallation is more than just as a base. X-Ray structures of cyclometallated complexes [MCl{C₆H₄-2-C(H)NCH₂CH₂OMe-κC,N}(η-ring)](M = Ir, Rh ring = Cp*; M = Ru, ring = p-cymene), [MCl{C₆H₄-2-C(H)NCH₂CH₂OMe-κC,N}Cp*](M = Ir, Rh), [RuCl(η²-O₂CMe)(p-cymene)] and [IrCl₂(NH₂Ph)Cp*] are reported.

Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes.

A Gd(III) complex bearing pendant acetoxymethyl esters is activated on exposure to porcine liver esterase; the 84% increase in relaxivity is a result of suppression of HCO₃ ⁻/CO₃ ²⁻ binding by the resulting negative charge.