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Tuning the Cell Uptake and Subcellular Distribution in BODIPY–Carboranyl Dyads: An Experimental and Theoretical Study
Author(s) -
LabraVázquez Pablo,
FloresCruz Ricardo,
GalindoHernández Aylin,
CabreraGonzález Justo,
GuzmánCedillo Cristian,
JiménezSánchez Arturo,
Lacroix Pascal G.,
Santillan Rosa,
Farfán Norberto,
Núñez Rosario
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202002600
Subject(s) - bodipy , lipophilicity , fluorophore , carborane , sonogashira coupling , chemistry , partition coefficient , fluorescence , hela , boron , biophysics , combinatorial chemistry , stereochemistry , cell , biochemistry , organic chemistry , catalysis , palladium , physics , quantum mechanics , biology
A set of BODIPY‐carboranyl dyads synthesized by a Sonogashira cross‐coupling reaction, where different C‐substituted ortho ‐ and meta ‐carboranyl fragments have been linked to a BODIPY fluorophore is described. Chemical, photophysical and physicochemical analyses are presented, including NMR and single XRD experiments, optical absorption/emission studies and partition coefficient (log P ) measurements. These studies, supported by DFT computations (M06‐2X/6‐31G**), provide an explanation to the largely divergent cell income that these fluorescent carboranyl‐based fluorophores display, for which a structural or physicochemical explanation remains elusive. By studying the cell uptake efficiency and subcellular localization for our set of dyads on living HeLa cells, we tracked the origins of these differences to significant variations in their static dipole moments and partition coefficients, which tune their ability to interact with lipophilic microenvironments in cells. Remarkably, m ‐carboranyl‐BODIPY derivatives with a higher lipophilicity are much better internalised by cells than their homologous with o ‐carborane, suggesting that m ‐isomers are potentially better theranostic agents for in vitro bioimaging and boron carriers for boron neutron capture therapy.