Amphiphilic Polymer-Based Fluorescent Probes for Enantioselective Recognition of Amino Acids and Amino Alcohols

Amphiphilic polymer-based fluorescent probes were synthesized by conducting atom transfer radical polymerization of N-isopropylacrylamide in the presence of a 3,3’-diformyl-1,1’-BINOL-based diinitiator. The probes were soluble in both water and common organic solvents and had unique solution properties such as lower critical solution temperature (LCST) and cononsolvency.
Optically pure polymer probes in combination with Zn(II) in aqueous solution (BICINE buffer at pH = 8.80) showed highly enantioselective fluorescence enhancement in the presence of a number of amino acids. It was found that chloroform can be used to extract the aqueous polymer-Zn(II)-amino acid solution and the resulting chloroform extract maintained the highly enantioselective fluorescence response. Thus, the enantiomeric composition of a chiral amino acid can be determined in the two immiscible solvents of water and chloroform. The aqueous polymer-Zn(II)-amino acid solution showed LCST at 34 degree celsius above which the polymer-Zn(II)-amino acid adduct precipitated out. Measuring the fluorescence of the precipitate redissolved in the aqueous buffer solution showed the retention of the high enantioselectivity. Both the chloroform extraction and the thermo-induced precipitation have allowed the fluorescence response of the sensor toward amino acids to be measured away from the original substrate solution. These two strategies should minimize the interference by other reaction components on the fluorescence measurement when the sensor is applied to analyze the asymmetric reaction screening experiments.
Optically pure polymer probes in combination with Zn(II) in water and methanol showed highly enantioselective fluorescence enhancement in the presence of five amino alcohols. In addition, optically pure and racemic probes exhibited a unique cononsolvency property. Mixing an aqueous solution of an optically pure polymer probe and Zn(II) with a dichloromethane solution of (S)- or (R)-amino alcohols led to the formation of polymer films at the interface of the water and dichloromethane phases. The polymer films were separated and showed highly enantioselective fluorescence enhancement in DMSO solution. The cononsolvency of this PNIPAM-based BINOL probes allows the sensor-substrate adduct to be readily separated from the original solution which should greatly reduce the interference of other components on the fluorescence measurement when the substrate is produced from a catalyst screening experiment.
When the polymers were treated with a mixture of the enantiomers of an amino alcohol, no fluorescence enhancement was observed unless one of the enantiomers was in excess of the other. This large nonlinear effect allows the racemic polymer probe to be used to determine the ee of the amino alcohol which represents the first example to use a racemic fluorescent probe to determine the ee of a chiral molecule.