SURFACE ENHANCED RAMAN SCATTERING-ELECTROCHEMICAL METHODS FOR CHARACTERIZATION OF SELECTED THERAPEUTIC DRUGS: SPECTROSCOPIC AND DFT STUDY. PhD thesis, King Fahd University of Petroleum and Minerals.

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Arabic Abstract

يعد استخدام مناهج التحليل الطيفي والكهروطيفي للكشف عن التراكيز المنخفضة للمركبات العضوية مجالًا بحثياً نشطًا. في هذه الدراسة، تم استخدام مطيافية رامان ذات السطح المحسن مدعمة بالتقنيات الكهروكيميائية للقيام بالتحليل النوعي والكمي لبعض المركبات العضوية المختارة والتي تستعمل في صناعة الأدوية وكذلك مبيدات الأعشاب ، وهي بروكايين ، سولينداك ، حمض الفيلاريك ، هيدروكسي كارباميد ، لينورون و 1-ميثوكسي-1-ميثيل-3-فينيل يوريا. كان الهدف الرئيسي هو تطوير بروتوكولات تحليلية حساسة لاستشعار وتوصيف هذه المركبات النشطة حيوياً. تم تحضير عدد من المواد البلازمية ذات البنية النانوية التي تنتح تحسيناً ملموساً حين تطبيق مطياف الرامان. تم توصيف هذه المواد النانوية بأدوات مختلفة كالتحليل الطيفي للأشعة تحت الحمراء (FTIR) ، وامتصاص الأشعة فوق البنفسجية ، والفحص المجهري الإلكتروني النفقي (TEM) ، والتحليل الطيفي للإلكترون بالأشعة السينية (XPS) والتحليل الطيفي للأشعة السينية المشتتة للطاقة ( EDX). تم فحص النشاط الكهروكيميائي للمواد باستخدام مقياس الجهد الدوري الكهروكيميائي (CV) والتحليل الطيفي الكهروكيميائي (EIS). تم استخدام هذه المواد النانوية رامان ذات السطح المحسن (SERS) للكشف والتوصيف منخفض التركيز. SERS هي تقنية حساسة وتوفر معلومات البصمة الجزيئية للمركبات. في SERS ، يتم تحسين إشارة Raman عندما يمتص جزيء التحليل على سطح المواد الهيكلية النانوية ويكون التحسين ناتجًا عن آليات نقل الشحنات الكهرومغناطيسية. تم تحسين إشارة SERS بشكل أكبر من خلال دمج التقنيات الكهروكيميائية، وتم حساب الخصائص الجزيئية والالكترونية للأنظمة المدروسة نظريًا باستخدام نظرية كثافة الدالة (DFT) ، ولقد تم توثيق جميع النتائج وبالتفصيل في وحدات هذا البحث. استنتجنا من هذا البحث أن التقنيات الطيفية الكهروكيميائية المستخدمة، أعني SERS و EC-SERS ، أثبتت أنها نهج سلس وفعال للتحليل الكمي للأدوية العلاجية والمركبات النشطة حيوياً ، وان هناك مجال كبير لتعزيز قدرتها وفعاليتها بصورة اكبر، ونعتقد انها تمثل تقنيات واعدة للمستقبل لتطوير أجهزة قياسات حساسة سهلة الاستخدام ومنخفضة التكلفة، يمكن ان توظف في المستشفيات ومحطات

English Abstract

The use of spectroanalytical approaches for detecting low concentrations of organic compounds in a variety of media is an active direction of research that intersects with vital medical, environmental and energy sectors. In this study, Raman and electrochemical techniques were employed for the qualitative and quantitative analysis of selected widely used therapeutic drugs and organic herbicides, namely procaine, sulindac, velaric acid, hydroxycarbamide, linuron and 1-methoxy-1-methyl-3-phenylurea. The main objective was to develop sensitive analytical protocols for the sensing and characterization of these bioactive compounds. Various nanostructured plasmonic materials were developed and characterized by using Raman spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), UV-vis absorption, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and energy dispersive X-ray spectroscopy (EDX). The electrochemical activity of the developed nanomaterials was investigated using electrochemical cyclic voltammetry (CV) and electrochemical impendence spectroscopy (EIS). These nanomaterials were implemented to enhance the Raman scattering light and enable us to apply the surface-enhanced Raman scattering (SERS) spectroscopic method for low concentration detection and characterization. SERS is a sensitive technique that provides fingerprint information of the compounds under study. Raman signals are enhanced when an analyte molecule is appropriately adsorbed on the surface of nanostructured materials, and the observed enhancement results from either electromagnetic or charge transfer mechanisms, or the combination of both. It has been noticed that SERS signals were further improved by incorporating electrochemistry. Furthermore, structural and electronic properties of studied therapeutic systems were theoretically predicted using density functional theory (DFT) and were correlated with our spectroscopic observations. To begin this research, the SERS based approach was employed to establish a method for quantification of valeric acid (VA). Spherically structured Ag-NPs were utilized for the trace detection of VA in aqueous media, and a wide dynamic range with a lower detection limit (1 x 10-10 M) could be achieved. The vibrational modes in the free form VA molecules and with the Ag-NPs interactions responsible for the SERS enhancement were analyzed via density functional theory (DFT) calculations. Next, the identification and quantification of sulindac using the surface-enhanced Raman scattering (SERS) technique and employing silver nanoparticles (AgNPs) substrates led to an unprecedented sensitivity of this drug of a wide dynamic range (1 x 10-2 M to 1 x 10-9 M) and a low detection limit (1 x 10-10 M). The SERS peaks resulting from the solvent DMSO molecules and the target sulindac drug molecules were carefully analyzed and properly interpreted. Molecular modeling results for the interaction of sulindac molecules with silver nanoparticles were correlated with the experimental findings. Significant enhancements, due to charge transfer processes, in the Raman bands at 1111, 1653, 1607 and 1340 cm-1 corresponding to the -S=O stretching, -C=O stretching, -C=C- stretching and ring stretching vibrations were observed. In the next part of the research which involved an intensive amount of work, SERS spectroscopy was implemented for the determination of procaine in aqueous media by utilizing gold nanoparticles (AuNPs) as an active substrate. The intensity enhancement obtained for a number of Raman peaks was employed to develop a reliable quantitative determination approach for procaine in aqueous solutions. Such an approach exhibited a high sensitivity and reproducibility with a reasonably wide linear dynamic range. The limit of detection of procaine achieved was up to 1 × 10–10 M. This has been outstanding compared with other methods such as chromatography and electrochemical methods. We continued these efforts by developing an electrochemically modulated sensing approach for the quantitative detection of procaine using in-situ SERS. This integrated approach is known as electrochemical-SERS or simply EC-SERS. A fluorine-doped tin oxide electrode modified using silver carbon nanosphere (AgCNS-FTO) was designed for this purpose, electrochemically evaluated, and used as an efficient substrate. The investigation of the electrochemical interaction of procaine molecules towards the modified electrode revealed that upon the optimum electrochemical pre-concentration potential (-0.1 V) and time (400 s), significant enhancements in the intensity of key Raman peaks corresponding to the NH2 bending, C=C stretching, CH2 twisting and C-N stretching modes could be observed. The reported approach enabled a remarkable sensitivity and selectivity towards procaine, resulting in an unprecedented detection limit down to the level of 10-13 M. The reproducibility and stability of the modified FTO electrode were ensured over a duration of one month, and a low RSD of 2.4% was achieved. In the next effort, we synthesized palladium-based highly reduced graphene oxide (Pd-HRG) with localized surface plasmon resonance (LSPR) properties as an effective SERS substrate. Its utility in the highly sensitive detection of procaine was tested. LSPR excitations are critical towards achieving sizable spectral enhancements of the Raman scattered light. The Pd-HRG nanocomposite showed a remarkable LSPR response with a Raman enhancement factor of 8.7 x 102. The Pd-HRG is employed to modify fluorine doped tin oxide electrode (Pd-HRG/FTO), resulted with an enhancement factor of 7.5 x 104 corresponding to the EC-SERS technique with reproducible and reliable result even in real urine sample. Moreover, the anti-cancer drug hydroxycarbamide (HC) was analyzed and characterized with EC-SERS approach using gold-coated copper oxide (Au-CuOx) circular nanoplates (CNPs). Several prominent Raman peaks associated with HC and ascribed by the NCN bending, CN stretching, NO stretching, CO stretching and NH2 wagging vibrational modes showed substantial enhancements upon the electrochemically induced interaction between the SERS substrate and the drug molecules. A limit of detection of one-tenth of nanomolar concentration was achieved under the optimum conditions. The SERS investigations were extended to cover some bioactive compounds used in the herbicides industry. Here, the monitoring of organic herbicides linuron and 1-methoxy-1-methyl-3-phenylurea (MMPU) were carried out by employing nuclear magnetic resonance (NMR) and Raman spectroscopic techniques supported with DFT to investigate the conformational behavior and electronic aspects of linuron In conclusion, spectroscopic and electro-spectroscopic techniques, namely SERS and EC-SERS, have been shown to be a sensitive analytical approach for the quantitative analysis of certain therapeutic drugs and other bioactive compounds used as herbicides and anti-cancer drugs. This work has potential and can lead to the development and design of sustainable sets of detective devices with affordable cost. Such devices can be easily applied in point-of-care stations in hospitals and medical sectors, as well as QA labs in environmental agencies and industry.

Item Type:	Thesis (PhD)
Subjects:	Chemistry
Department:	College of Chemicals and Materials > Chemistry
Committee Advisor:	Al-Saadi, Abdulaziz Abdulrahman
Committee Members:	Khalid R., Alhooshani and Tawfik A., Saleh and Anvarhussein, Isab and Basheer, Chanbasha
Depositing User:	MUHAMMAD HAROON (g201708930)
Date Deposited:	29 Dec 2022 07:32
Last Modified:	29 Dec 2022 07:32
URI:	http://eprints.kfupm.edu.sa/id/eprint/142280