Vanillylmandelic acid (VMA) and homovanillic acid (HVA) are diagnostic markers of neuroblastoma. The purpose of this study was to understand the reason for the discrimination of structural analogues (VMA and HVA) onto a graphite electrode coated with an electrochemically oxidized urea derivative. Density functional theory calculations (DFT), FTIR spectroscopic measurements, and electrochemical impedance spectroscopic measurements were used in this work. Density functional theory calculations (DFT) were used to identify the most suitable binding sites of the urea derivative and to describe possible differences in its interaction with the studied analytes. The FTIR measurement indicated the enhancement and disappearance of NH vibrations on graphite and platinum surfaces, respectively, that could be connected to a different orientation and thus provide accessibility of the urea moiety for the discrimination of carboxylates. Additionally, the higher the basicity of the anion, the stronger the hydrogen-bonding interaction with -NH-groups of the urea moiety: VMA (pKb = 10.6, KAds = (5.18 ± 1.95) × 105) and HVA (pKb = 9.6, KAds = (4.78 ± 1.58) × 104). The differential pulse voltammetric method was applied to detect VMA and HVA as individual species and interferents. As individual analytes, both HVA and VMA can be detected at a concentration of 1.99 × 10-5 M (RSD ≤ 0.28, recovery 110-115%).

Department of Analytical Chemistry University of Chemistry and Technology Technická 5 166 28 Prague Czech Republic

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Cebula J., Fink K., Boratyński J., Goszczyński T.M. Supramolecular chemistry of anionic boron clusters and its applications in biology. Coord. Chem. Rev. 2023;477:214940. doi: 10.1016/j.ccr.2022.214940. DOI

Hirao T., Kishino S., Haino T. Supramolecular chiral sensing by supramolecular helical polymers. Chem. Commun. 2023;59:2421–2424. doi: 10.1039/d2cc06502a. PubMed DOI

Guo C., Sedgwick A.C., Hirao T., Sessler J.L. Supramolecular fluorescent sensors: An historical overview and update. Coord. Chem. Rev. 2021;427:213560. PubMed PMC

Goel N., Kumar N. Supramolecules: Future Challenges and Perspectives. In: Goel N., Kumar N., editors. Pharmaceutical Applications of Supramolecules. Springer; Cham, Switzerland: 2022. pp. 319–328. DOI

Wang S., Liu Y., Zhu A., Tian Y. In vivo electrochemical biosensors: Recent advances in molecular design, electrode materials, and electrochemical devices. Anal. Chem. 2023;95:388–406. PubMed

Ross J.A., Davies S.M. Screening for neuroblastoma: Progress and pitfalls. Cancer Epidemiol. Biomark. Prev. 1999;8:189–194. PubMed

Parisi M.T., Eslamy H., Park J.R., Shulkin B.L., Yanik G.A. 131I-Metaiodobenzylguanidine theranostics in neuroblastoma: Historical perspectives; practical applications. Nucl. Med. 2016;46:184–202. doi: 10.1053/j.semnuclmed.2016.02.002. PubMed DOI

Miekus N., Kowalski P., Oledzka I., Plenis A., Bien E., Miekus A., Krawczyk M., Adamkiewicz-Drozynska E., Baczek T. Cyclodextrin-modified MEKC method for quantification of selected acidic metabolites of catecholamines in the presence of various biogenic amines. Application to diagnosis of neuroblastoma. J. Chromatogr. B. 2015;1003:27–34. PubMed

Khamlichi R.E., Bouchta D., Anouar E.H., Atia M.B., Attar A., Choukairi M., Tazi S., Ihssane R., Faiza C., Khalid D., et al. A novel l-leucine modified sol-gel-carbon electrode for simultaneous electrochemical detection of homovanillic acid, dopamine and uric acid in neuroblastoma diagnosis. Mater. Sci. Eng. C. 2017;71:870–878. doi: 10.1016/j.msec.2016.10.076. PubMed DOI

Shishkanova T.V., Broncová G., Fitl P., Král V., Barek J. Voltammetric detection of catecholamine metabolites using Tröger’s base modified electrode. Electroanalysis. 2018;30:734–739. doi: 10.1002/elan.201700635. DOI

Baluchová S., Barek J., Tomé L.I.N., Brett C.M.A., Schwarzová-Pecková K. Vanillylmandelic and homovanillic acid: Electroanalysis at non-modified and polymer-modified carbon-based electrodes. J. Electroanal. Chem. 2018;821:22–32. doi: 10.1016/j.jelechem.2018.03.011. DOI

Shishkanova T.V., Sinica A. Electrochemically deposited cobalt bis(dicarbollide) derivative and the detection of neuroblastoma markers on the electrode surface. J. Electroanal. Chem. 2022;921:116674. doi: 10.1016/j.jelechem.2022.116674. DOI

Boiocchi M., Del Boca L., Esteban-Go’mez D., Fabbrizzi L., Licchelli M., Monzani E. Nature of urea−fluoride interaction:  incipient and definitive proton transfer. J. Am. Chem. Soc. 2004;126:16507–16514. doi: 10.1021/ja045936c. PubMed DOI

Salvadori K., Páleš J.M., Shishkanova T.V., Trchová M., Fajgar R., Matějka P., Cuřínová P. An electrochemical sensor for detection of neuroblastoma markers: Complexation studies as a tool for the selection of a suitable receptor for electrode coating. ChemPlusChem. 2022;87:e202200165. doi: 10.1002/cplu.202200165. PubMed DOI

Magar H.S., Hassan R.Y.A., Mulchandani A. Electrochemical impedance spectroscopy (EIS): Principles, construction, and biosensing applications. Sensors. 2021;21:6578. doi: 10.3390/s21196578. PubMed DOI PMC

Brett C.M.A. Electrochemical impedance spectroscopy in the characterisation and application of modified electrodes for electrochemical sensors and biosensors. Molecules. 2022;27:1497. doi: 10.3390/molecules27051497. PubMed DOI PMC

Millner P.A., Caygill R.L., Conroy D.J., Shahidan M.A. Impedance Interrogated Affinity Biosensors for Medical Applications: Novel Targets and Mechanistic Studies. Volume 45 Woodhead Publishing Ltd.; Cambridge, UK: 2012.

Randviir E.P., Banks C.E. Electrochemical impedance spectroscopy: An overview of bioanalytical applications. Anal. Methods. 2013;5:1098–1115. doi: 10.1039/c3ay26476a. PubMed DOI

Rushworth J.V., Ahmed A., Griffiths H.H., Pollock N.M., Hooper Millner P.A. A label-free electrical impedimetric biosensor for the specific detection of Alzheimers amyloid-beta oligomers. Biosens. Bioelectron. 2014;56:83–90. doi: 10.1016/j.bios.2013.12.036. PubMed DOI

Zhang J.K., Wu Y., Zhang B.B., Li M., Jia S.R., Jiang S.H., Zhou H., Zhang Y., Zhang C.Z., Turner A.P.F. Label-free electrochemical detection of tetracycline by an aptamer nano-biosensor. Anal. Lett. 2012;45:986–992. doi: 10.1080/00032719.2012.670784. DOI

Dhillon S., Kant R. Theory for electrochemical impedance spectroscopy of heterogeneous electrode with distributed capacitance and charge transfer resistance. Chem. Sci. J. 2017;129:1277–1292. doi: 10.1007/s12039-017-1335-x. DOI

Guler Z., Erkoc P., Sarac A.S. Electrochemical impedance spectroscopic study of single-stranded DNA-immobilized electroactive polypyrrole-coated electrospun poly(ε-caprolactone) nanofibers. Mater. Express. 2015;5:269–279. doi: 10.1166/mex.2015.1249. DOI

Yan J., Yuan W., Tang Z., Xie H., Mao W., Ma L. Synthesis and electrochemical performance of Li3V2(PO4)3−xClx/C cathode materials for lithium-ion batteries. J. Power Sources. 2012;209:251–256. doi: 10.1016/j.jpowsour.2012.02.110. DOI

Kütt A., Selberg S., Kaljurand I., Tshepelevitsh S., Heering A., Darnell A., Kaupmees K., Piirsalu M., Leito I. pKa values in organic chemistry—Making maximum use of the available data. Tetrahedron Lett. 2018;59:3738–3748. doi: 10.1016/j.tetlet.2018.08.054. DOI

Li Q., Batchelor-McAuley C., Compton R.G. Electrooxidative decarboxylation of vanillylmandelic acid: Voltammetric differentiation between the structurally related compounds homovanillic acid and vanillylmandelic acid. J. Phys. Chem. B. 2010;114:9713–9719. doi: 10.1021/jp104137p. PubMed DOI

Gates S.C., Sweeley C.C., Krivit W., DeWitt D., Blaisdell B.E. Automated metabolic profiling of organic acids in human urine. II. Analysis of urine samples from “healthy” adults, sick children, and children with neuroblastoma. Clin. Chem. 1978;24:1680–1689. doi: 10.1093/clinchem/24.10.1680. PubMed DOI