Fluorescent cationic probes for nuclei of living cells: why are they selective? A quantitative structure–activity relations analysis

Horobin, R. W. , Stockert, J. C. and Rashid-Doubell, F. (2006) Fluorescent cationic probes for nuclei of living cells: why are they selective? A quantitative structure–activity relations analysis. Histochemistry and Cell Biology, 126(2), pp. 165-175. (doi: 10.1007/s00418-006-0156-7) (PMID:16463179)

Abstract

Selectivity of nuclear probes is controlled by competitive accumulation of the probe by cellular organelles as well as the high affinity for nucleic acids. Physicochemical features of probes which favor nucleic acid binding include cationic character and a planar aromatic system above a minimum size. Features of probes which permit entry into cells are low protein and lipid binding. Features which reduce accumulation in non-nuclear sites include high base strength and hydrophilicity of the cation. The overall quantitative structure–activity (QSAR) model specifying nuclear accumulation may be expressed as follows: CBN<40; 8>log Pneutral species>0; AI<8; Z>0; -5<log Pcation<0; pKa>10; LCF>17; LCF/CBN>0.70 (where CBN is the conjugated bond number, log Px the logarithm of the water–octanol partition coefficient of species x, AI the amphilicity index, Z the electric charge, pKa the negative logarithm of the equilibrium constant for the free base–protonated base reaction, and LCF the largest conjugated fragment). Preliminary applications of the QSAR model—to the selection of anticancer drugs, minimization of dye and drug toxicity and the designed synthesis of fluorescent probes—are outlined.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Horobin, Dr Richard
• Authors: Horobin, R. W., Stockert, J. C., and Rashid-Doubell, F.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Histochemistry and Cell Biology
• Publisher: Springer
• ISSN: 0948-6143
• ISSN (Online): 1432-119X
• Published Online: 07 February 2006