Spectroelectrochemical and Voltammetric Studies of L‐DOPA

The electrooxidation of L -dopa at GC electrode was studied by in situ UV-vis spectroelectrochemistry (SEC) and cyclic voltammetry. The mechanism of electrooxidation and some reaction parameters were obtained. The results showed that the whole electrooxidation reaction of L -dopa at glassy carbon (GC) electrode was an irreversible electrochemical process followed by a chemical reaction in neutral solution (EC mechanism). The spectroelectrochemical data were treated by the double logarithm method together with nonlinear regression, from which the formal potential E⁰=228 mV, the apparent electron-transfer number of the electrooxidation reaction αn=0.376 (R=0.99, SD=0.26), the standard electrochemical rate constant k⁰=(3.93±0.12)×10⁻4 cm s⁻¹ (SD=1.02×10⁻²), and the formation equilibrium constant of the following chemical reaction k_c=(5.38±0.34)×10⁻¹ s⁻¹ (SD=1.02×10⁻²) were also obtained.     

Preparation of both enantiomers of β-(3,4-dihydroxybenzyl)-β-alanine, higher homologues of Dopa

β²-(3,4-Dihydroxybenzyl)-β-alanine [β²-Homo-Dopa, 1] is a novel β-amino acid homologue of Dopa, the most successful therapeutic agent in the treatment of Parkinson's disease. Enantioenriched (R)-1 and (S)-1 were obtained via the diastereoselective alkylation of enantiopure pyrimidinone (R)- and (S)-3, chiral derivatives of β-alanine, with veratryl iodide. The major diastereomeric products (2S,5R)-4 and (2R,5S)-4 were hydrolyzed with 57% HBr, and the desired β-amino acids were purified by silica gel chromatography. Alternatively, enantioenriched (R)- and (S)-1 were prepared by means of the highly diastereoselective alkylation (3,4-dimethoxybenzyl iodide) of open-chain β-aminopropionic acid derivatives (R,R,S)-8 and (S,S,R)-8 containing the chiral auxiliary α-phenylethylamine. Finally, nearly enantiopure (R)- and (S)-1 were obtained by resolution of racemic N-benzyloxycarbonyl-2-(3,4-dibenzyloxybenzyl)-3-aminopropionic acid, rac-12, with (R)- or (S)-α-phenylethylamine, followed by catalytic hydrogenolysis.     

Electrochemical Behaviour and Rapid Determination of L‐Dopa at Electrochemically Pretreated Screen Printed Carbon Electrode

A simple and rapid voltammetric method based on a disposable electrochemically pretreated screen‐printed carbon electrode is proposed for the determination of L ‐dopa. Under optimum differential pulse voltammetry conditions a limit of detection of 3.6×10^?7 M for L ‐dopa was obtained. The method was successfully applied to the determination of L ‐dopa in a commercial pharmaceutical formulation.     

固定化假单胞菌产L-多巴

选择海藻酸钙和聚乙烯醇凝胶为固定化载体包埋假单胞菌（Ｐｓｅｕｄｏｍｏｎａｓｓｐ．），以提高该菌以Ｌ－酪氨酸为底物生产Ｌ－多巴的效率．海藻酸钙和聚乙烯醇固定的假单胞菌分别将发酵周期缩短了８和１４ｈ．半连续发酵的结果表明，海藻酸钙和聚乙烯醇固定化细胞分别能重复使用５次和１４次，Ｌ－多巴生产效率比游离细胞分别提高了１６％和１６０％．聚乙烯醇固定化细胞经过热处理和在生理盐水中振荡处理可明显提高Ｌ－多巴的生产效率和产量，过高的底物加入量不利于固定化细胞的重复使用     

Voltammetric Determination of L‐Dopa on Poly(3,4‐ethylenedioxythiophene)‐Single‐Walled Carbon Nanotube Composite Modified Microelectrodes

In the present communication, it is shown that platinum microelectrodes electrochemically coated with a composite of poly(3,4‐)ethylenedioxythiophene and single‐walled carbon nanotubes (PEDOT/SWNT) enable determinations of 3,4‐dihydroxy‐L ‐phenylalaines (L ‐dopa) in neutral phosphate buffer solutions containing an excess of ascorbic acid. The interpenetrated networked nanostructure of the composite was characterized by scanning electron microscope (SEM) and Raman spectroscopy. It is shown that the presence of the composite gives rise to an increase in the electroactive area of an order of magnitude in compared to the area for the bare microelectrodes. The composite film‐coated microelectrode, which yielded reversible cyclic voltammograms for the ferro/ferricyanide redox couple for scan rates between 0.01 and 0.10 V s^?1, also gave rise to two well‐resolved oxidation peaks for L ‐dopa and ascorbic acid (AA). The latter effect, which was not seen in the absence of the composite, enabled differential pulse voltammetric determinations of L ‐dopa in the concentration range between 0.1 to 20 μM with a detection limit of 100 nM.     

Theoretical study of the adsorption of DOPA-quinone and DOPA-quinone chlorides on Cu (1 0 0) surface

The marine mussel secreted adhesive proteins and could bind strongly to all kinds of surfaces. Studies indicated that there was an unusual amino acid 3,4-dihydroxy-l-phenylanine (DOPA). DOPA could be oxidized to DOPA-quinone easily, which had a superior ability to on surface directly. The technology of electrolyzing seawater was employed to generate HOCl solution to react with DOPA-quinone and form DOPA-quinone chlorides (DOPA-quinone-Cl) to hinder the adhesion. However, the detailed hinder-mechanism remained unknown to be fully explained. Herein, using quantum chemical density functional theory methods, we have systematically studied three kinds of adsorption for DOPA-quinone and DOPA-quinone-Cl on Cu (1 0 0) surface: hydroxyl oxygen-side vertical, carbonyl oxygen-side vertical, amino N-terminal vertical adsorptions and carried out geometry optimization and energy calculation. The results showed that two molecules could absorb on the Cu (1 0 0) through hydroxyl oxygen-side vertical adsorption, while the other two kinds of adsorption could not form an effective adsorption. Calculations of adsorption energy for hydroxyl oxygen-side vertical adsorption indicated that: after HOCl modification, adsorption energy decreased from −247.2310 kJ/mol to −177.0579 kJ/mol for DOPA-quinone and DOPA-quinone-Cl; and the Mulliken Charges Populations showed that the electrons transferred from surface to DOPA-quinone-Cl was less than that to DOPA-quinone, namely, the fewer the number of electrons transferred, the weaker interaction between molecular and surface. After the theoretical calculation, we found that the anti-foul goal had been achieved by electrolysis of seawater to generate HOCl to modify DOPA-quinone, which led to the reduction of adsorption energy and transferred electrons.     

非样品手性配体交换毛细管电泳测定手性多巴

以L-多巴为测定目标, 以天然芳香氨基酸为替代样品, 建立了以非样品α-羟基酸为手性配体, 以铜和镍等二价金属为中心离子的手性配体交换毛细管电泳新方法. 当弱配位的α-羟基酸与中心离子的摩尔比大于6∶1时, 所建立的方法即可实现对D,L-氨基酸和D,L-多巴的基线分离, 可用于口服多巴药片含量的测定, 检测出质量分数为0.5%的异构体杂质, 其定量的线性范围是0.025~2.5 mmol/L, 回收率为96.3%. 据此方法测得某商品药片的实际含量(质量分数)为标称值的(97.33±0.70)%.     

A new validated HPLC method for the determination of levodopa: Application to study the impact of ketogenic diet on the pharmacokinetics of levodopa in Parkinson's participants

A simple, accurate, and reproducible HPLC‐UV method has been developed and validated for the quantification of levodopa (l ‐Dopa) in human plasma. The method involves a simple protein precipitation procedure to extract both l ‐Dopa and methyldopa, the internal standard. The chromatographic analysis was achieved on a Shimadzu LC 20A HPLC system equipped with a Zorbax Eclipse XDB C₁₈ column and an isocratic mobile phase consisting of 20 mm KH₂PO₄ (pH 2.5) and methanol (95:5, v/v) run at a flow rate of 1 mL/min. The UV detection wavelength was set at 230 nm. The method exhibited good linearity (R² > 0.999) over the assayed concentration range (0.1–10 μg/mL) and demonstrated good intra‐ and inter‐day precision and accuracy (relative standard deviations and the deviation from predicted values were <15%). This method was also successfully applied for studying the potential effect of ketogenic diet on the pharmacokinetics of l ‐Dopa in Parkinson's participants. Our data analysis indicates that ketogenic diet does not significantly affect the pharmacokinetics of l ‐Dopa.