Dual Mode Chip Enantioselective Express Discrimination of Chiral

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Dual mode chip enantioselective express discrimination of chiral amines by the wettability-based mobile app and portable SERS measurements Olga Guselnikova, Pavel S. Postnikov, Andrii Trelin, Václav Švor#ík, and Oleksiy Lyutakov ACS Sens., Just Accepted Manuscript • DOI: 10.1021/acssensors.9b00225 • Publication Date (Web): 04 Apr 2019 Downloaded from http://pubs.acs.org on April 7, 2019

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Dual mode chip enantioselective express discrimination of chiral amines by the wettability-based mobile app and portable SERS measurements Olga Guselnikovaa,b, Pavel Postnikova,b*, Andrii Trelina, Vaclav Švorčíka, Oleksiy Lyutakova,b* a

Department of Solid State Engineering, University of Chemistry and Technology, 16628 Prague,

Czech Republic bResearch

School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University,

Russian Federation ______________________ * Corresponding author: [email protected], [email protected] Keywords: double-mode analysis, chiral detection, wettability, SERS, chiral amines Abstract Dual-mode functional chip for chiral sensing based on the mobile phone wettability measurements and portable Surface-enhanced Raman spectroscopy (SERS) is reported. The plasmon-active regular gold grating surface was covalently grafted with chiral recognition moieties, L- or D-enantiomers of tartaric acid making possible stereoselective discrimination of chiral amines. Chiral sensing of amines includes two modes of analysis, performed subsequently on the one chip surface with portable instruments (mobile phone equipped with a camera and developed app «Dropangle», and portative Raman spectrometer). Firstly, the wettability changes, caused by enantioselective entrapping of chiral amines, are monitored and analyzed by our mobile phone app, allowing detection of the optical configuration and concentration of enantiomers with one order of magnitude accuracy. Secondly, SERS measurement on the same chip provides information about the chemical structure of entrapped amines and allows calculating the enantiomeric excess with great accuracy. The applicability of the developed chip is demonstrated on the variety of chiral amines, including the tyrosine, cysteine, dopamine (DOPA) and dextromethorphan in analytical solutions and in commercially available DOPA-containing drug. Moreover, we demonstrate that the chips could be regenerated and used repeatedly for at least 5 cycles.

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Chiral discrimination has become one of the most desirable analytical methods in stereoselective quality control and validation of pharmaceuticals1-3. A range of drugs and bioactive compounds exist in chiral form, but only the active enantiomer of a chiral drug should be brought to the consumer. For this reason, the recognition of enantiomers is of vital importance in both the drug development process and quality control4-6. Chiral analysis can be performed using various approaches, including X-ray crystallography, high-performance liquid and gas chromatography, circular dichroism, nuclear magnetic resonance and others7-11. Despite all of the previous efforts, the issue of the design of the sensors combing chiral resolution and determination is still challenging. The sensor systems based on Surface-enhanced Raman spectroscopy (SERS) are a highly prospective candidate for the chiral discrimination due to its high sensitivity, short time of analysis and reliability of results

12-18.

Generally, for the SERS-based enantioselective discrimination the

grafting of chiral-recognition layer to plasmon substrate is used 19-26. However, most of these SERS sensor systems can be applied only to a limited range of analytes like chiral alcohols, which restrict the usability of SERS-based chiral discrimination 19-24. On the other hand the multi-mode detection approaches have recently been attracting great attention as one of the attempts to simplify the detection procedure. This approach provides subsequent or parallel information about multiple parameters of a single analytical system and simplifies significantly the required procedures via preliminary selection of samples

27-30.

Among

various surface properties, which can be utilized for the first stage of multi-mode detection, wettability is one of the most powerful and simple one. Especially attractive is the wettability-based analytical procedure for chiral discrimination of enantiomers, which makes possible to translate the weak chiral signals from enantiomers into the macroscopic property and in this way to amplify it significantly 31, 32. Because of wettability measurements easiness and its high sensitivity, the design of chiral multi-mode sensors including contact angle determination is highly appealing and prospective

31-34.

In turn, the wettability-based chiral discrimination can be followed or combined

with more complex method, to enhance the analysis reliability. Up to date, the wettability has been applied for the amplification of the electrochemical signal for the chiral discrimination of D/L sugars 35,

fluorescence signal for enantiomers of amino-containing alcohols 36 and colorimetric signal 37. To our best knowledge, the dual mode detection systems based on the wettability

measurement in combination with the Surface-Enhanced Raman Spectroscopy sensing have yet not been reported. Here, dual-mode chiral resolution and detection of chiral amines (namely an important chiral drug L/D-DOPA, L/D-Cysteine, L/D-Tyrosin and dextromethorphan) by the wettability-based mobile phone app and portable SERS measurements is proposed. Results and Discussion 2 ACS Paragon Plus Environment

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The design and creation of the double-functional chip for the discrimination of enantiomers using mobile phone-based wettability measurements (by Android app) and SERS-based chiral recognition is schematically shown in Fig. 1. The thickness of the gold layer (25 nm) was optimized using the deposition of Rhodamin 6G and measuring of its SERS response (Fig. S1). As a starting point the surface plasmon-polariton (SPP) supporting periodical gold gratings were covalently functionalized with L- or D-tartaric acid (L or D-TA), serving as a chiral recognition moiety for selective entrapping of enantiomers (the chips abbreviations are Au-L-TA and Au-D-TA). The functionalization was performed through spontaneous grafting by 4-aminobenzenediazonium tosylate (ADT-NH2), followed by the EDC/NHS coupling of amino groups with L- or D-tartaric acid (Fig. 1). The decoration of gold surface was proved using the Raman and XPS spectroscopies (Fig. S2, Tab. 1). Both methods convincingly demonstrate the surface grafting by ADT-NH2 and TA coupling. Since the initial surface pattern was chosen to provide the effective SPP excitation, which is a necessary condition of effective portable SERS measurements

16-18

and for precisecontact angle

(CA) measurement as well, the conservation of main grating parameters is necessary for further utilization of double-functional chip. Fig. 2 presents the surface morphology, measured by AFM on the pristine, grafted with ADT-NH2 and decorated with TA samples. It is seen that the shape of the grating, its periodicity and amplitude remain unchanged during the surface functionalization. The chips functionality was preliminary tested on the two model compounds - enantiomers of cysteine and tyrosine. Both compounds contain the chiral carbon connected with amino-group in their structure and can be enantioselectively entrapped by grafted TA enantiomers. The wettability-based discrimination of chiral amines was performed by making a photo of 2 µl drop by the mobile telephone camera and immediate determination of CAs value with developed «Dropangle» application (application description is given in SI). The results of mobile-based chiral discrimination are presented in the Fig. S4. The measured CAs of analyte drops deposited on the gold grating surface, show clear dependence on the presence of cysteine or tyrosine enantiomers. In particular, the strong increase of CAs on the Au-L-TA chips was observed in the presence of L-enantiomers of the both amines (Fig. S4A and S4C). Oppositely, the chip interaction with chiral irrersponsive enantiomers (D-tyrosine and D-cysteine) on Au-L-TA, does not affect the CAs values. So that, using the mobile phone and the proposed chip we are able from the measured dependence of CAs on L-amino acid concentrations to recognize the presence of specific enantiomer up to 10-11M concentrations level.. Similar results were observed in the case of Au-D-TA chips, where the presence of D-enantiomers of chiral amines results in the distinct change in CAs values (Fig. S4B and S4D). The drastic changes of CAs (for instance, 35° difference in the case on D-tyrosine and L-tyrosine on Au-L-TA) make the


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wettability measurement with mobile phone camera and the developed application a superior estimative/qualitative tool for the detection of chiral amines. The presence of chiral amines in the analytical solution can be detected by CAs measurements but their molecular structure remains still unknown. In order to improve the reliability of chiral detection and identification a dual-mode analytical approach was chosen with the SERS measurements as the second stage, performed with portable, fiber-optic coupled, Raman spectrometer. After the CAs were determined, the substrates were flushed with water and used for the SERS measurement and identification of enantiomer structure. Results are presented in the Fig. S3 (the spectra after substraction of SERS spectra of L- or D- Tartaric acid grafted gold gratings are shown for better visibility). It is evident that the interaction of Au-D-TA or Au-L-TA chips with chiral irresponsive enantiomers does not produce any additional spectral features (i.e. closed to zero additional SERS signal) but interaction with chiral responsive enantiomers of both amines leads to significant changes in the SERS spectra. The characteristic Raman bands (see SI) perfectly correspond with the molecular structure of entrapped amines

38.

So that, it was demonstrated that

created dual-mode system allows to selectively detect chiral amines and to estimate the enantiomers concentration by simple and unpretentious CA measurements in the first step and provide the information about the molecular structure of chiral amines with the precise recognition of enantiomers by SERS measurements, performed on the same chip. In the next step, we tested the present approach for enantioselective discrimination of biologically relevant compounds - 3-(3,4-dihydroxyphenyl)-L-alanine (DOPA)39. Results of DOPA enantioselective discrimination, based on the mobile-phone CAs measurements are presented in the Fig. 3 (error bars represent the measurement standard deviation). It is evident that the CAs of analyte solutions are strongly affected by the presence of chiral responsive DOPA enantiomer. The rise in CA was observed with increasing of L-DOPA concentration in the drop deposited on the Au-L-TA chip, while in the case of D-DOPA the CA values remain unchanged regardless of the analyte concentration. Similar phenomena were observed in the case of D-DOPA for both Au-D-TA and AuL-TA chips. The observed changes of CAs should be attributed to the entrapping of chiral analytes from the deposited drops by grafted TA molecules. As a result, the surface polarity changes dramatically and leads to apparent increase of CA values. We also tested the enantiomers entrapping by XPS technique and the results indicated an increase of surface carbon and nitrogen concentration after the interaction with DOPA solutions (Fig. S5 - several concentrations were used) even in the case of pM concentration. The increase of DOPA concentration in solution leads to an increase of carbon and nitrogen surface concentrations, indicating the greater amount of entrapped organic molecules. Thus, 4 ACS Paragon Plus Environment

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observed increase in CA should be undoubtedly attributed to the changes in the surface polarity due to the entrapping of larger number of DOPA molecules from the deposited drops with growing enantiomer concentration. Special attention also deserves very small deviations of the measured CAs from the fitted values (i.e., experimental errors bars presented in Fig. 3 are in the 2-3% range). Such perfect ordering of the experimental results should be attributed to regular surface morphology (regular grating surface) as well as to the homogeneous coverage of the surface with TA molecules. For comparison, the CAs, measured on the flat, grafted TA with surface is presented in the Fig. S6. It must also be noted that the accuracy of the obtained results may be affected by the time taken to measure the drop CA after its deposition. For an example, the Fig. S7 shows the results of time-resolved CA changes. As one would expect, the gradual decrease of drop volume due to evaporation leads to some decrease in the CA value. We also used developed wettability-based approach for the analysis of two enantiomer mixtures of DOPA, designated as Mixtures I (constant concentration of D-DOPA –10-4 M, the gradual increase of L-DOPA) and Mixtures II (constant concentration of L-DOPA - 10-4 M, the gradual increase of D-DOPA). Obtained results (Fig. 3, Tab. 2) clearly indicate that CAs values are sensitive only to chiral responsive enantiomer concentrations (L-DOPA in the case of Au-L-TA and D-DOPA in the case of Au-D-TA). The presence of chiral irresponsive enantiomer in the mixture does not affect the resulting CAs values. So that, the possibility of enantiomer mixture analysis within an order of magnitude (accuracy can be approximately estimated from the error bars in the Fig. 3) using the subsequent measurements, performed with a mobile application on two chips is demonstrated. In the next step we performed an additional comparison of mobile phone-based CA measurements, determined with app «Dropangle» application, with corresponding CAs values obtained with professional equipment (Kruss system). The results presented in Fig. S8 and show that the careful estimation of CAs with mobile app provides almost the same values of CAs and reproducibility as in the case of goniometer measurements. We also performed the detailed study of the phenomena, which may induce such apparent wettability changes or their absence. The chemical composition and surface morphology of Au-D-TA and Au-L-TA chips were analyzed before and after the DOPA enantiomers entrapping and the results are presented in the Tab. 1 and Fig. S9. As is evident the interaction of Au-L-TA chip with L-DOPA led to significant changes in surface chemical composition and also affects the grating morphology. Oppositely, interaction with D-DOPA does not result in any changes. The same dependences were also observed in the case of Au-D-TA chips entrapping of D-DOPA leads to the changes in the surface composition and morphology. Since the wettability is a function of both, surface morphology and chemistry, we can conclude that 5 ACS Paragon Plus Environment

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enantioselective recognition of chiral responsive DOPA enantiomer leads to pronounced changes of surface properties and wettability, which in turn makes the mobile phone-based determination of DOPA enantiomers in their mixture possible. In the next step, the dual-mode functional chips were used for chiral SERS recognition with portable Raman spectrometer, providing information about the structure of analyte. More informative SERS results, obtained on the Au-L-TA and Au-D-TA chips, after preceding CAs measurements, are presented in the Fig. 4A (the spectra after subtraction of the spectra of Au-L-TA or Au-D-TA are given; error bars represent the measurements standard deviation). Marked changes in SERS signal after the interaction of Au-L-TA chip with L-DOPA (or Au-D-TA with D-DOPA) make possible to determine the molecular structure of entrapped molecules. Following Raman bands, characteristic for DOPA, are visible: 1600, 1630 cm-1 N-H and C=O; 1344,1294,1056 cm-1N-H and C-N; 808,774, 715 cm-1 C-N and N-H; 543, 503 cm-1 N-C-O. In the irresponsive pair (interaction of Au-L-TA chip with D-DOPA or vice versa) no spectral changes are detected. The pronounced DOPA SERS peak located at 774 cm-1was used for the construction of chip calibration curve, presented in the Figs. 4A and 4B. As is evident the 774 cm-1 peak intensity linearly increases as a function of the logarithm of DOPA enantiomers concentration. In the case of a chiral irresponsive pair of DOPA with SERS chip, 774 cm-1 peak intensity has been almost constant, close to zero value. The additional estimation of the homogeneity of DOPA entrapping was explored using the SERS mapping (in this case the Raman signal was measured using the microscopy objective) and the results are presented in Fig. S10. As is evident, the drop deposition results in the creation of a „boundary“ area, where the Raman intensity is higher but it is lower in adjacent surrounding areas. In turn, in the center of the drop-deposited area, the intensity seems to be significantly more homogeneous. So, precise SERS measurements, performed with fiber-coupled Raman spectrometers, requires accurate signal adjustment into the center of the drop-deposited area (or measurement of full drop-deposited area). We also evaluate the reproducibility of SERS results (see Fig. S11 and Tab. S1) as a function of DOPA enantiomer concentration. A statistical evaluation of the obtained results indicates that perfect reproducibility can be achieved up to 10-12 M concentration of both enantiomers. The calibration curves, presented in the Figs. 4B and 4C were used for the accurate determination of L- and D-DOPA concentrations in their mixture from the measured intensity of 774 cm-1 peak. Comparison of the real concentrations of DOPA enantiomers with SERS measured ones, presented in the Tab. 2, demonstrates the perfect agreement between each other. So that, the above results demonstrate that the CAs measurements with previously described «Dropangle» app makes possible to recognize the presence of chiral amines in the analyte and determine their concentration with one order of magnitude accuracy. In the second stage portable SERS measurements can be used 6 ACS Paragon Plus Environment

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to recognize the molecular structure of amine and determine its concentration with even greater accuracy. The formation of salts between TA and DOPA can be inverted at low pH values (pH=6.4), returning the surface properties to its pristine initial state (pristine CA value, absence of DOPA related Raman bands). Several examples of Au-L-TA chip regeneration and application are presented in the Fig. 5. As is evident (Figs. 5B, C, D), after the chip regeneration, the further CAs measurement allows to identify the presence of D- and L-DOPA enantiomers. The measured CAs show excellent convergence and do not change after five cycles of chips utilization/regeneration. The similar situation was observed for SERS measurements: the characteristic DOPA Raman bands occur after the interaction with L-DOPA and disappear after Au-L-TA chip regeneration. Finally, we demonstrated the advantages of proposed dual-mode functional chips and analytical procedure for the analysis of DOPA-containing commercially available drug (Fig. S14) and for enantioselective discrimination of dextromethorphan (Fig. S12). Producer claims that one tablet contains 120 mg of DOPA, including minimum 60 mg of L-isomer. According to the developed procedure, the tablet of the commercially-available drug was used for double-mode analysis. In the first case, the DOPA molecules were extracted from the tablet using the standard procedure 40, and the extract was drop-deposited on Au-L-TA and Au-D-TA chips. Measured CAs values show the presence of L-DOPA and D-DOPA in the drug (Fig. S14B vs. Fig. 3). According to calibration equation (Fig. 4B), the concentration of D-DOPA was calculated to be 10-8.23 M (11.6 mg), while in the case of Au-L-TA according to Fig. 4C, the concentration of L-DOPA was 10-6.44M (71.5 mg). Therefore the final amount of L/D-DOPA is 83 mg, while enantiomeric excess is 72%. Comparison of the above results with the information from drug distributor and control measurements, performed by chiral HPLC are is given in Tab. S3. The perfect agreement of control HPLC results with our measurements proves the applicability and usefulness of proposed dual-mode chip. In the next step we demonstrated the applicability of the proposed analytical approach for the analysis of another relevant compound - dextromethorphan (DXM) which is known to be an effective antitussive drug. However, its L-isomer form, levomethorphan, produces morphine-like effects 41. The wettability and SERS enantioselective discrimination of DXM, performed on the Au-L-TA and Au-D-TA chips are presented in the Fig. S12. In the SERS spectra the DXM characteristic Raman bands (see SI) are observed, indicating the DXM entrapping on the Au-D-TA chip. In the case of Au-L-TA substrate, no CAs changes or additional SERS features were detected. So, these results demonstrate the high potential of the proposed dual-mode sensor for express detection and recognition of relevant drug, based on portable, simple and very fast methods.


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We also estimated expected costs of proposed SERS chips to further emphasize their benefits. We take into consideration all expendable materials, usage of machines, chemical reagents from local or European producers as well as payment for production, packing and sales. Results of calculation are presented in the Tab. S2 and it is evident that if 10 thousand chips would be produced per month, the estimated price of 1 chip would be 3.48 €. However, increasing the number of produced functional SERS chip to 100 thousand decreases their cost up to 2.86 € a piece. Since similar (but nonfunctionalized, i.e. achiral) SERS substrates cost more than 10 $ 42, 43 per piece, we can conclude that proposed chiral SERS chip combines both unique analytical possibilities and cost effectiveness. Conclusion The design, preparation, and utilization of dual-mode functional chips, for the two steps chiral discrimination of chiral amines are described. The plasmon-active gold grating surface was decorated with L- or D-isomers of Tartaric acid, able to enantioselectivly entrap the chiral amines from solution. The chip implementation involves two steps procedure: determination of analytes from contact angles (CA) measurements performed with the camera of mobile phone and developed with original Android software «Dropangle», followed by the portable SERS measurements. In the first phase the presence of enantiomers is detected, both in their “pure” or mixed solutions. Additionally, the enantiomers concentration in mixture can be estimated roughly from CA measurements. From the next SERS measurement, performed with portable, fiber-optic coupled spectrometer, information about the molecular structure of chiral amines is obtained and enantiomers concentrations is determined with higher precision. The developed approach was preliminarily tested on the two model compounds (tyrosine, and cysteine). Then the advantages of the proposed user-friendly way for enantioselective amines discrimination on the real sample of DOPA-containing drug and dextromethorphan was demonstrated. Sensing abilities of the proposed dual-mode chip toward chiral amines offer great promises for the portative, fast and sensitive analyses.

Materials and Methods Detailed description of used materials and experimental procedures for grating preparation, diazonium modification and Grafting of L- or D – Tartaric acid is given in SI44. Measurement techniques Wettability (contact angle) investigations – concentration dependence 8 ACS Paragon Plus Environment

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For the mobile-phone assisted wettability detection, the Au-Lor Au-D -TA sensor was placed parallel to the optical axis, in such a way that the cross-sectional view of water droplet can be captured by the camera in mobile phone. For a user-friendly portable module, we have also developed an Android-based operating system application “Dropangle.” This app was successfully installed and tested in android version 7.0 smart-phone. Detailed description and demonstration of the application are shown in SI. For a control, the contact angles (CAs) were first measured with Drop Shape Analyzer – DSA100 (Kruss, Germany) at 10 positions (drop volume - 2 μL) at room temperature after ≈ 8 sec after deposition using aqueous solutions of L/D -DOPA, L/D-cystein, L/D-Tyrosine and Dextromethorphan. Then, the CAs on the same samples were measured (drop volume was the same as in the case on goniometer) by mobile phone application «Dropangle» (see Fig. S13). Raman spectroscopy investigations– concentration dependence. The Raman spectroscopy measurements were performed after the wettability characterization on the same chip. The chip surface before Raman measurements were carefully washed by water to remove all residual, unspecifically absorbed analytes, dried in a desiccator and then immediately analyzed by Raman spectroscopy. Raman scattering was measured on a portable ProRaman-L (Laser power 30 mW, 785 nm excitation wavelength) Raman spectrometer equipped with fiber optic probe for outdoor analysis. Spectra were measured 30 times, each of them with 3 s accumulation time. For the estimation of SERS convergence, the 10 drops of enantiomers (10-14, 10-12, and 10-10 M of L- or D-DOPA) were deposited on the 15 substrates (150 points were evaluated for each enantiomer and concentration). In the case of all other concentrations, the measurements (wettability or SERS) were performed with at least five drops per one chip (in all cases three chip were used), and obtained results were used for the estimation of the measurement standard deviation. All deviations and other statistical values were calculated by Hypothesis Tests program (allowed to remove up to 15% of outliers to increase the measurement accuracy). Raman spectroscopy investigations– selectivity study. For the estimation of the selectivity, following aqueous mixtures of L-DOPA and D-DOPA were used: L/D=10-4/10-8, 10-4/10-10, 10-4/10-12 (for Au-L-TA) and D/L=10-4/10-8, 10-4/10-10, 10-4/1012

(for Au-D-TA). For each mixture CAs were measured by mobile phone application «Dropangle»

and the Raman spectroscopy measurements were performed on the same chip. Investigations of commercially available DOPA-containing drug. One capsule of drug (0.78 g) was overnight extracted by 10 ml of aqueous 0.1 M HCl. Producer claimed minimum 120 mg of DOPA (6.10-4mol) in one capsule. The suspension was centrifuged and 10 mkl were collected and diluted in 100 ml of water. This solution was used for the 9 ACS Paragon Plus Environment

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wettability and SERS measurements. Control measurements of L/D-DOPA concentrations were carried out by chiral HPLC using an Chirobiotic-T chiral column on Shimadzu Liquid chromatographic, LC-10AS apparatus. Supporting Information Detailed description of used materials and experimental procedures; Description of Android-based «Dropangle» mobile application; characterization of chemical modification of gold gratings (SERS and XPS mesurements); L/D-Tyrosin and L/D-Cystein wettability measurements on Au-L-TA and Au-D-TA grafted chips surfaces; SERS sensing of L- or D-Cystein and L- or D-Tyrosine on the grafted chips surafaces; AFM scans of gold grating grafted with L-tartaric acid or D-tartaric acid before and after interaction with DOPA enantiomers; enantioselective discrimination of Dextromethorphan using the wettability and SERS measurements. Acknowledgment This work was supported by the GACR under the project P108/12/G108 and Tomsk Polytechnic University (project VIU-RSCABS-195/2018). References [1] Collins, J. T.; Kuppe. Ch.; Hooper, D. C.; Marco. K. S.; Ventsislav, C.; Valev, K. Chirality and Chiroptical Effects in Metal Nanostructures: Fundamentals and Current Trends. Adv. Opt. Mat. 2017, 5, 16, 1700182. [2] Jedrzejewska, H.; Szumna, A. Making a Right or Left Choice: Chiral Self-Sorting as a Tool for the Formation of Discrete Complex Structures. Chem. Rev., 2017, 117, 6, 4863–4899. [3] Lang, J. C.; Armstrong, D. W. Chiral surfaces: The many faces of chiral recognition. Curr. Opin. Colloid Interface Sci. 2017, 32, 94–107. [4] Foley, P.; The L-DOPA story revisited. Further surprises to be expected? In: Riederer P. et al. (eds) Advances in Research on Neurodegeneration. Springer, Vienna, 2000. [5] Chen, X.; Kang, Y.; Zeng, S. Analysis of stereoisomers of chiral drug by mass spectrometry. Chirality 2018, 30, 5, 609-618. [6] Habala, L.; Horáková, R.; Čižmáriková, R. Chromatographic separations based on tartaric acid and its derivatives. Mon. Chem. 2018, 149, 5, 873-882. [7] Zhao,X.-L.; Tian, D.; Gao, Q.; Sun, H.-W.; Xu, J.; Bu, X.-H.; A chiral lanthanide metal–organic framework for selective sensing of Fe(III) ions. Dalton Trans. 2016, 45, 1040-1046. [8] Guebitz, G.; Schmid, M. G. Chiral separation principles in chromatographic and electromigration techniques. Mol. Biotechnol., 2006, 32, 3, 159–180. 10 ACS Paragon Plus Environment

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composition

with

in

vitro

anti-inflammatory

and

antioxidant

activity

of

Mucunamacrocarpa beans: A future drug for Parkinson treatment. Asian Pac. J. Trop. Biomed. 2017, 7, 12, 1097-1106. [41] Benson, W. M.; Stefko, P. L.; Randall, L. O. Comparative pharmacology of levorphan, racemorphan and dextrorphan and related methyl ethers. J. Pharmacol. Exp. Ther. 1935, 109, 2, 189200. [42] https://oceanoptics.com/product/sers/ [43] http://www.silmeco.com/products/sers-substrate-serstrate/ [44] Guselnikova, O.; Postnikov, P.; Elashnikov, R.; Trusova, M.; Kalachyova, Y.; Libansky, M.; Barek, J.; Kolska, Z.; Svorcik, V.; Lyutakov, O. Surface modification of Au and Ag plasmonic thin films via diazonium chemistry: Evaluation of structure and properties. Coll. Surf. A 2017, 516, 274285. Figure caption Fig. 1 Schematic of the preparationof L- or D-Tartaric acid coated gold gratings. Fig. 2 AFM images (morphology) of gold grating, modified by ADT-NH2and then grafted by L- and D-Tartaric acid. Fig. 3 Chirality-triggered wettability - relationship between CAs (using solution of L-DOPA, DDOPA and mixtures I and II) on (A) - gold grating grafted with L-Tartaric acid and (B) - with DTartaric acid vs .logarithm of the concentrations of D-DOPA and L-DOPA.


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Fig. 4 (A) - sensing of L- and D-DOPA in different concentrations on gold gratings grafted with Lor D-Tartaric acid and corresponding dependences of SERS peak intensity on analyte concentration (spectra after subtraction spectra of Au-L-TA (B) and Au-D-TA (C) correspondently). Fig. 5 (A)-scheme of Au-L-TA sensor regeneration, (B) - wettability cycles; (C) - SERS spectra recorded during recyclable L-DOPA detection at the concentration of 10-12 M and (D) -the corresponding variation of the relative Raman intensity at 774 cm-1.


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Table 1. Results of XPS measurements on Au-L or D-TA before and after entrapping of L/DDOPA Surface atom element concentration (at %) Au-L-TA Au-L-TA+LDOPA Au-L-TA+DDOPA Au-D-TA Au-D-TA-DDOPA Au-D-TA+LDOPA

C 77.4

O 16.5

Au 5.5

N 0.6

79.2

19.6

0.55

0.65

77.5

16.6

5.3

0.6

77.4

16.5

5.5

0.6

78.9

19.7

0.8

0.6

77.6

16.7

5.1

0.6

Table 2. SERS detection of L/D-DOPA in the racemic mixture on gold gratings modified by D/LTartaric acid.

Au-D-Tartaric acid CL-DOPA

CD-DOPA

Intensity at

(M)

(M)

774 cm

-4

10

-4

10

-4

10

10 10 10

-1

Au-L-Tartaric acid Calculated concentration of D-DOPA (M)

-8

116.2±0.6

10

-10

78.5±1.1

10

-12

41.3±0.4

10

CD-DOPA (M)

-8.05

10

-10.10

10

-12.03

10

CLDOPA

(M)

-4

10

-4

10

-4

10


Intensity at -1

774 cm

Calculated concentration of L-DOPA (M)

-8

118.8±0.6

10

-8.03

-10

77.6±0.4

10

-12

43.5±0.9

10

-10.20

-12.04

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Fig.1


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Fig. 2


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Fig. 3


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Fig. 4


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Intensity at 774 cm-1, -

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Fig. 5


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TOC


Dual Mode Chip Enantioselective Express Discrimination of Chiral

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