Department of Chemistry , Xavier University of Louisiana , New Orleans 70125 , United States.
College of Chemistry and Chemical Engineering , Lanzhou University , Lanzhou 730000 , China.
Anal Chem. 2018 Apr 3;90(7):4733-4740. doi: 10.1021/acs.analchem.7b05361. Epub 2018 Mar 22.
This work aims to face the challenge of monitoring small molecule drugs accurately and rapidly for point-of-care (POC) diagnosis in current clinical settings. Overdose of acetaminophen (AP), a commonly used over the counter (OTC) analgesic drug, has been determined to be a major cause of acute liver failure in the US and the UK. However, there is no rapid and accurate detection method available for this drug in the emergency room. The present study examined an AP sensing strategy that relies on a previously unexplored strong interaction between AP and the arginine (Arg) molecule. It was found that as many as 4 hydrogen bonds can be formed between one Arg molecule and one AP molecule. By taking advantages of this structural selectivity and high tenability of hydrogen bonds, Arg, immobilized on a graphene surface via electrostatic interactions, was utilized to structurally capture AP. Interestingly, bonded AP still remained the perfect electrochemical activities. The extent of Arg-AP bonds was quantified using a newly designed electrochemical (EC) sensor. To verify the feasibility of this novel assay, based on multihydrogen bond manipulated single-molecule recognition (eMuHSiR), both pharmaceutical and serum sample were examined. In commercial tablet measurement, no significant difference was seen between the results of eMuHSiR and other standard methods. For measuring AP concentration in the mice blood, the substances in serum, such as sugars and fats, would not bring any interference to the eMuHSiR in a wide concentration range. This eMuHSiR method opens the way for future development of small molecule detection for the POC testing.
这项工作旨在应对当前临床环境中即时护理(POC)诊断中小分子药物精确和快速监测的挑战。在美国和英国,过量使用醋氨酚(AP)这种常用的非处方(OTC)止痛药已被确定为急性肝衰竭的主要原因。然而,在急诊室中,还没有针对这种药物的快速准确的检测方法。本研究探讨了一种基于 AP 与精氨酸(Arg)分子之间以前未被探索的强相互作用的 AP 传感策略。结果发现,多达 4 个氢键可以在一个 Arg 分子和一个 AP 分子之间形成。利用这种结构选择性和氢键的高稳定性,通过静电相互作用将 Arg 固定在石墨烯表面上,用于结构捕获 AP。有趣的是,结合的 AP 仍然保持着完美的电化学活性。使用新设计的电化学(EC)传感器来定量 Arg-AP 键的程度。为了验证这种新型分析的可行性,基于多氢键操纵的单分子识别(eMuHSiR),对药物和血清样本进行了检测。在商业片剂测量中,eMuHSiR 和其他标准方法的结果之间没有明显差异。对于测量小鼠血液中的 AP 浓度,血清中的物质,如糖和脂肪,在宽浓度范围内不会给 eMuHSiR 带来任何干扰。这种 eMuHSiR 方法为未来的即时检测小分子检测开辟了道路。