DANPY (dimethylaminonaphthylpyridinium): an economical and biocompatible fluorophore

Abstract

DANPY-1 is a prototype for a family of NLO-active, low-toxicity fluorescent dyes for biological imaging and biophotonics.

Derivatives of DANPY (Dialkylaminonaphthylpyridinium), a DNA-Binding Fluorophore: Practical Synthesis of Tricyclic 2-Amino-6-bromonaphthalenes by Bucherer Reaction

“…Structures were optimized in chloroform solvent using Gaussian 09 at the CAM-B3LYP/6-31+G­(d) level of theory. Properties were calculated in chloroform at the same level of theory, which has been determined to furnish good estimates on the relative β and λ max of chromophores and was effective for predicting the relative optical properties of DANPY-1 and similar dyes . Octanol–water partition coefficient (log P ) values, a common measure of hydrophobicity, were estimated using the ChemAxon consensus logP method in MarvinSketch. , Data from the computational screen is compiled in Table .…”

“…As illustrated in Scheme , 2-pyrrolidino-6-bromo-naphthalene ( 2 ) forms in 87% yield upon base-promoted N , N -dialkylation of 1 with 1,4-dichlorobutane [tetrabutylammonium iodide (TBAI) and dimethyl sulfoxide (DMSO), 95 °C] under Finkelstein conditions. Subsequent Suzuki coupling with pyridine 4-boronic acid under the previously optimized conditions [1 mol % Pd 2 (dba) 3 , 4 mol % SPhos, and 4:1 dimethylformamide (DMF)–EtOH, 90 °C] gives intermediate 2-pyrrolidino-6-pyridyl-naphthalene ( 3 , not shown in Scheme ) in >60% recrystallized yield on gram scale without chromatography. In a third and final step, site-selective N -methylation in warm acetonitrile gives dye 4 in 76% yield as thin red needles after passage through a plug of silica gel in 10:1 dichloroethane–MeOH and recrystallization from chloroform.…”

“…The identity of the anion stems from the choice of electrophile used to build the alkylpyridinium cation, and primary bromides have also proven effective. As shown in Scheme , N -alkylation of the pyridine derived from 6 , with bromoalkanes linked to 7-hydroxy coumarin (umbelliferone) give multifunctional fluorophores 12 and 13 as red, amorphous solids . A first step in preparing these variants was to secure 1-bromoalkyl ethers of the coumarin ( 11a , b ) by Williamson reaction with the corresponding 1,6- and 1,8-dibromoalkanes.…”

“…These dye molecules may be suitable for photonic devices that utilize DNA-derived polymer waveguides . DANPY-1 was initially developed to be doped into such waveguides as an electro-optic material. ,,, Prior attempts at such systems required blending the DNA with a dye (such as Disperse Red 1), a cetyltrimethylammonium surfactant, and in many cases a cross-linking agent for thermal stability. As single entities, 12 and 13 are unique in merging a cationic chromophore (that can act as a counterion for DNA) with a cross-linkable coumarin surfactant that undergoes [2 + 2] cycloaddition in the presence of UV light .…”

“…Dyes with nonlinear optical (NLO) activity are of interest for both photonic systems and a number of imaging techniques in living cells. , The fluorescent dye molecule DANPY-1 is both NLO-active and biocompatible, possessing a range of other useful properties such as low toxicity, high photostability, and high sensitivity of its absorbance and fluorescence properties to its dielectric environment . First intended for use in DNA-based photonic systems, , DANPY-1 was designed by joining structural features of the common intercalating agent ethidium bromide , with those of the NLO-active dye DAST , (Figure ).…”