Beyond the TPP<SUP>+</SUP> "gold standard": a new generation mitochondrial delivery vector based on extended PN frameworks

• Type: Article in International Scientific Journal
• Date: 2023

Authors

Ong, HC (Author) Other; Coimbra, JTS (Author) Other; Ramos, MJ (Author) FCUP; Xing, BG (Author) Other; Pedro A Fernandes (Author) FCUP; García, F (Author) Other

Journal

Title: Chemical Science

Vol. 14

Pages: 4126-4133

ISSN: 2041-6520

Publisher: Royal Society of Chemistry

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00Y-752

DOI: 10.1039/d2sc06508h

Abstract (EN): Mitochondrial targeting represents an attractive strategy for treating metabolic, degenerative and hyperproliferative diseases, since this organelle plays key roles in essential cellular functions. Triphenylphosphonium (TPP+) moieties - the current gold standard - have been widely used as mitochondrial targeting vectors for a wide range of molecular cargo. Recently, further optimisation of the TPP+ platform drew considerable interest as a way to enhance mitochondrial therapies. However, although the modification of this system appears promising, the core structure of the TPP+ moiety remains largely unchanged. Thus, this study explored the use of aminophosphonium (PN+) and phosphazenylphosphonium (PPN+) main group frameworks as novel mitochondrial delivery vectors. The PPN+ moiety was found to be a highly promising platform for this purpose, owing to its unique electronic properties and high lipophilicity. This has been demonstrated by the high mitochondrial accumulation of a PPN+-conjugated fluorophore relative to its TPP+-conjugated counterpart, and has been further supported by density functional theory and molecular dynamics calculations, highlighting the PPN+ moiety's unusual electronic properties. These results demonstrate the potential of novel phosphorus-nitrogen based frameworks as highly effective mitochondrial delivery vectors over traditional TPP+ vectors.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8