Nanoparticle-based Chemiluminescence for Chiral Discrimination of Thiol-Containing Amino Acids

www.nature.com/scientificreports OPEN Received: 18 May 2018 Accepted: 4 September 2018 Published: xx xx xxxx Nanoparticle-based Chemiluminescence for Chiral Discrimination of Thiol-Containing Amino Acids Maryam Shahrajabian1, Forough Ghasemi1 & M. Reza Hormozi-Nezhad1,2 The ability to recognize the molecular chirality of enantiomers is extremely important owing to their critical role in drug development and biochemistry. Convenient discrimination of enantiomers has remained a challenge due to lack of unsophisticated methods. In this work, we have reported a simple strategy for chiral recognition of thiol-containing amino acids including penicillamine (PA), and cysteine (Cys). We have successfully designed a nanoparticle-based chemiluminescence (CL) system based on the reaction between cadmium telluride quantum dots (CdTe QDs) and the enantiomers. The different interactions of CdTe QDs with PA enantiomers or Cys enantiomers led to different CL intensities, resulting in the chiral recognition of these enantiomers. The developed method showed the ability for determination of enantiomeric excess of PA and Cys. It has also obtained an enantioselective concentration range from 1.15 to 9.2 mM for PA. To demonstrate the potential application of this method, the designed platform was applied for the quantification of PA in urine and tablet samples. For the first time, we presented a novel practical application of nanoparticle-based CL system for chiral discrimination. Chiral recognition is considered as one of the most essential yet difficult measurements of molecular recognition. Chiral identification is a key process in fields of biochemistry, biotechnology, modern chemistry, biology, development of asymmetric catalysts1, and production of pharmaceuticals2. Enantiomers of chiral molecules may express extremely different effects in terms of biochemical activities, potency, mechanism, metabolic pathways3, stereo-specific synthesis, production of pharmaceuticals2, toxicity, and metabolism1. For instance, in biological processes, enantiomers generally exhibit different pharmacological functions and toxicities on living organisms4. Human body responses differently to different enantiomers of some chiral compounds and only one enantiomer may interact desirably, while the other may induce serious dangerous effects5. Penicillamine (PA) is a critical chiral drug for many therapeutic applications. It exists in two isomeric forms, including D-penicillamine (D-PA) and L-penicillamine (L-PA). The important pharmaceutical form is D-PA which is used in the treatment of Wilson’s disease, rheumatoid arthritis, and hepatitis. D-PA is also applied for the prevention of infants’ retina disease in preterm infants4, and cystinuria5. It is also an important intermediate in many pharmaceutical syntheses. In addition, D-PA can be used as an antidote in some heavy-metal poisoning. In contrast, L-PA has been found to have toxic properties since it may contribute to several considerable adverse reactions like osteomyelitis and neuritis6. lt can also inhibit the action of pyridoxine7. Another thiol-containing amino acid, cysteine (Cys) has vital biological functions in neuronal tissues, metabolism, brain, detoxification, and protein synthesis8–10. Enantiomers of Cys express extremely different effects on fundamental physiological processes. As an example, L-Cys is essential for living beings and D-Cys is useful in tumor treatment11. Cys is useful for protecting normal tissues against the undesirable side effects of cancer chemotherapeutic agents and radiation treatment. Radioprotective and chemotherapeutic strategies might be developed using the D-Cys12. L-Cys aids many substantial cellular functions such as metabolism and detoxification. Low levels of L-Cys normally acts as a neuroprotective antioxidant in neuronal activity, while high levels of L-Cys may cause neurotoxic effects that may lead to following neuronal trauma like brain ischemia. In contrast, D-Cys does not lead to excitotoxic 1 Department of Chemistry, Sharif University of Technology, Tehran, 11155-9516, Iran. 2Institute for Nanoscience and Nanotechnology, Sharif University of Technology, Tehran, Iran. Correspondence and requests for materials should be addressed to M.R.H.-N. (email: ) Scientific REPOrTS | (2018) 8:14011 | DOI:10.1038/s41598-018-32416-z 1 www.nature.com/scientificreports/ Figure 1. The structure of the flow injection CL system platform. (PMT is photomultiplier tube). damage to the brain and protects cerebellar neurons from oxidative stress induced by hydrogen peroxide8. Thus the development of a simple method for chiral recognition of Cys and PA, and determination of their enantiomeric excess is extremely important in the fields of pharmaceutical science clinical medicine, and biochemistry. Different analysis methods including CL13, biamperometry14, fluorometry15–18, high-performance liquid chromatography19,20, and spectrophotometry21–24 have been proposed for the identification of D-PA. However, these methods cannot make an effective discrimination between D- and L- enantiomers. On the other hand, various analytical techniques, including high-performance liquid chromatography (HPLC), thin-layer chromatography (TLC), capillary electrophoresis (CE), gas chromatography, mass spectrometry25–36, circular dichroism (CD)37, fluorometry38, nuclear magnetic resonance (NMR) protocols39,40 and using chiral light fields41–44 have been reported to distinguish the chirality of PA, Cys, and other chiral compounds. However, most of these techniques have several drawbacks such as laborious setup process, expensive chiral columns, complicated sample pretreatment, complex operation process and high-cost chiral stationary phases or chiral selectors. Therefore, the design of inexpensive and simple methods for chiral recognition of enantiomers is still a great challenge. Intrinsic chirality of nanoparticles(NPs) and the relationship between the chirality of nanoparticles and chirality of molecules on their surface are interesting topics that have been extensively studied in the past years45–48. Chemical sensing based on nanoparticles has attracted research interests due to their unique size-dependent properties. The catalytic effect of NPs also leads to excellent CL signal amplification, leading to their efficient use in chemiluminescence (CL) sensors. Because of simple, inexpensive, and low background signal features, NP enhanced-CL systems can be used as efficient sensors49–52. There are few reports on NP-based recognition of chiral compounds53–58 but to the best of our knowledge, no study has so far been published on NP-based CL sensor for chiral discriminations. As we have reported previously, thioglycolic acid (TGA) capped cadmium telluride QDs (TGA-CdTe QDs) can act as an enhancer for the luminol–H2O2 CL system to generate strong CL radiation59. In the present work, a new CL method based on TGA-CdTe QDs has been proposed for t (...truncated)