Chiral Recognition Of Amino Acid And β-adrenergic Blockade Based On Resonance Rayleigh Scattering

Chirality is one of the essential attribute of the nature to the survival of humans, and the species of nature is always show a preference for one enantiomer of chiral drugs.The amino acid consist in life body are levorotatory, and the ribose that composition of nucleic are dextrorotatory. Stereoselectivity is one kind of characteristic in the enzymatic reaction, messenger-receptor interaction and the process of metabolism.Therefore, the metabolism and regulation of life process always show some sensitivity to stereochemistry, and show different response to one pair of enantiomers. For this reason, it is really important for the chiral recognition research of chiral drugs. In the text, simple, rapid and sensitivity resonance Rayleigh scattering assay was used to the chiral recognition research and simultaneous determination of two kinds of aromatic amino acids and three kinds of β-adrenergic blockades.In this work, tyrosine, phenylalanine, three kinds of β-adrenergic receptors（atenolol,metoprolol and propranolol） were used as research objects, and utilized silver nanoparticles（Ag NPs）, gold nanoparticles（Au NPs）, quantum dots（QDs） and dye（erythrosine B） as resonance Rayleigh scattering probe, study on the chiral recognition research and simultaneous determination of tyrosine, phenylalaine and β-adrenergic blockades based on resonance Rayleigh scattering assay. Investigated the spectral features（RRS spectrum, UV-vis spectrum and fluorescence spectrum）, the optimum experimental conditions and the influences of coexisting substances of every system,developed a RRS method for the chiral recognition research of amino acid and bisoprolol drugs. On the other hand, the reaction mechanism and reasons of RRS signal variation of every system were discussed, the new method also be used to the determination in real samples.Under the supports of two projects of National Natural Science Foundation of China（No.21175015; No.21475014）, the main research details are as follows:1. Chiral recognition of tyrosine enantiomers based on a decrease resonance scattering signals with silver nanoparticles as optical sensorA novel chiral sensing platform, employing silver nanoparticles capped with Nacetyl-L-cysteine（NALC-Ag NPs）, was utilized for the discrimination of L-tyrosine and D-tyrosine. This nanosensor, which could be used as an optical sensing unit and chiral probe, was characterized by transmission electron microscopy（TEM） and resonance Rayleigh scattering（RRS） spectroscopy. After the proposed sensing platform interacted with L-tyrosine and D-tyrosine, a decrease resonance scattering signal was only obtained from L-tyrosine. This phenomenon offered a useful assay for the selectivity and determination of L-tyrosine with RRS method. The linear range and detection limit of L-tyrosine were 0.2838-20.0 μg/m L and 0.0860 μg/m L, respectively.In addition, experimental factors such as acidity, interaction time and the concentration of enantiomers were investigated in regards to the effect on enantioselective interaction.2. Cu²⁺ functionalized N-acetyl-L-cysteine capped Cd Te quantum dots as a novel resonance Rayleigh scattering probe for the recognition of phenylalanine enantiomersA simple protocol that can be used to simultaneously determinate enantiomers is extremely intriguing and useful. In this study, we proposed a low-cost, facile, sensitive method for simultaneous determination. The molecular recognition of Cu²⁺functionalized N-acetyl-L-cysteine capped Cd Te quantum dots(Cu²⁺-NALC/Cd Te QDs)with phenylalanine（PA） enantiomers was investigated based on the resonance Rayleigh scattering（RRS） spectral technique. The RRS intensity of NALC/Cd Te QDs is very weak, but Cu²⁺ functionalized NALC/Cd Te QDs have extremely high RRS intensity,the most important observations are that PA could quench the RRS intensity of Cu²⁺-NALC/Cd Te QDs, and that L-PA and D-PA have different degree of influence. In addition, those experimental factors such as acidity, concentration of Cu²⁺ and reaction time were investigated in regards to their effects on enantioselective interaction. Finally,the applicability of the chiral recognized sensor for the ananlysis of chiral mixtures onenantiomers has been demonstrated, and the results that were obtained high precision（<4.63%） and low error（<3.06%）.3. Double-wavelength overlapping resonance Rayleigh scattering technique for the simultaneous quantitative analysis of three β-adrenergic blockadeFour simple and accurate spectrophotometric methods were proposed for the simultaneous determination of three β-adrenergic blockade, e.g. atenolol, metoprolol and propranolol. The methods were based on the reaction of the three drugs with erythrosine B（EB） in a Britton-Robinson buffer solution at p H 4.6. EB could combine with the drugs to form three ion-association complexes, which resulted in the resonance Rayleigh scattering（RRS） intensity enhanced significantly with new RRS peaks appeared at 337 nm and 370 nm, respectively. In addition, the fluorescence intensity of EB was also quenched. The enhanced scattering intensities of the two peaks and the fluorescence quenched intensity of EB were proportional to the concentrations of the drugs, respectively. What is more, the RRS intensity overlapped with the doublewavelength of 337 nm and 370 nm（so short for DW-RRS） was also proportional to the drugs concentrations. So, a new method with highly sensitive for simultaneous determination of three bisoprolol drugs was established. Finally, the optimum reaction conditions, influencing factors and spectral enhanced mechanism were investigated. The new DW-RRS method has been applied to simultaneously detect the three β-blockers in fresh serum with satisfactory results.4. Citric acid modified gold nanoparticles detection of the propranolol in the mixture of bisoprolol drugsIn this work, a highly sensitive, citrate anion-capped gold nanoparticles（Au NPs）based assay for the determination of propranolol in real samples with resonance Rayleigh scattering（RRS） and colorimetic was developed. When Au NPs were being prepared by sodium citrate reduction method, citrate anions self-assembled on the surface of Au NPs to form supermolecular complex anions, and on the other hand, in BR4.6 buffer solution, propranolol was positively charged and could bind with Au NPs to form larger aggregates through electrostatic force and hydrophobic effects, which results in the remarkable enhancement of RRS intensity and at the same time the color change of Au NPs solution is from red to blue via purple. Thus a highly sensitive RRSand colorimetric assay for detection of propranolol has been developed with the linear range of 0.2-5.2 μg/m L and 0.4-4.4 μg/m L, respectively. The optimum conditions of the reaction and influencing factors were investigated. In addition, the reaction mechanism and the reasons for the enhancement of RRS were discussed.