Novel main group molecules and complexes for biological systems application

Main group lipophilic cations for enhanced mitochondrial therapies:

Mitochondrial function is central to a wide range of biological processes in health and disease and there is considerable interest in developing small molecules that are taken up by mitochondria and act as either probes of mitochondrial function or therapeutics in vivo.

We are undertaking systematic and rational studies on different group 15 salts in order to optimize the selectivity towards mitochondria. Therefore, optimizing the concentration of drug needed to achieve an equivalent medical effect.

Our research has demonstrated and quantified the enhancement of the delivery of the “gold standard” mitochondrial targeting moiety, a triphenyl-phosphonium cation (TPP+), upon structural modification. This work underscores a series of molecular parameters that can be exploited to design future TPP mitochondrial delivery vectors with enhanced properties.

Selected publications:

  • Enabling Mitochondrial uptake of lipophilic dications using methylated triphenylphosphonium moieties.    Inorg. Chem., 2019, 58, 8293-8299. DOI:10.1021/acs.inorgchem.8b03380..
  • Rational Design of Triphenylphosphonium Derivatives for Enhanced Mitochondrial Uptake and Photodynamic Therapy.  Bioconjugate Chem., 2017, 28 590 – 599, DOI: 10.1021/acs.bioconjchem.6b00682mito-toc2