Synthesis of Pyrrolidine-Fused 1,3-Dithiolane Oligomers by the Cycloaddition of Polycyclic Dithiolethiones to Maleimides and Evaluation as Mercury(II) Indicators

The scandium triflate-catalyzed cycloaddition reaction of polycyclic 1,2-dithiolethiones to maleimides is described. The reaction constitutes an easy approach to linear as well as branched oligomeric cis-fused dihydro[1,3]dithiolo[4,5-c]pyrrole-4,6-dione rings interconnected by 3,5-diylidenethiomorpholine-2,6-dithione or ylidene-6-thioxo[1,2]dithiolo[3,4-b][1,4]thiazin-3-one groups. The presence of highly colored, highly polarized push−pull α,β- unsaturated thione groups in their structures make these compounds sensitive to the presence of mercury(II) cation in organic or mixed organic/aqueous solvents.Ministerio de Economía y Competitividad, Spain (Project CTQ2012- 31611), Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo (Project BU246A12-1), and the European Commission Seventh Framework Programme (Project SNIFFER FP7-SEC-2012-312411)

A sensitive nanosensor for the in situ detection of the cannibal drug

[EN] A bio-inspired nanodevice for the selective and sensitive fluorogenic detection of 3,4- methylenedioxypyrovalerone (MDPV), usually known as Cannibal drug, is reported. The sensing nanodevice is based on mesoporous silica nanoparticles (MSNs), loaded with a fluorescent reporter (rhodamine B) and functionalized on their external surface with a dopamine derivative (3), which specifically interacts with the recombinant human dopamine transporter (DAT), capping the pores. In the presence of MDPV, DAT detaches from the MSNs consequently causing rhodamine B release and allowing drug detection. The nanosensor shows a detection limit of 5.2 µM and it is able to detect the MDPV drug both in saliva and blood plasma samples.The authors thank the Spanish Government (projects RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE) and CTQ2017-87954-P) and the Generalitat Valencia (PROMETEO/2018/024) for support. E.G. is grateful to the Spanish MEC for her FPU grant. M.A. thanks her postdoctoral fellowship (PAID -10-17). The authors also thank the Electron Microscopy Service at the UPV for support.Garrido-García, EM.; Alfonso-Navarro, M.; Díaz De Greñu-Puertas, B.; Marcos Martínez, MD.; Costero, AM.; Gil Grau, S.; Sancenón Galarza, F.... (2020). A sensitive nanosensor for the in situ detection of the cannibal drug. ACS Sensors. 5(9):2966-2972. https://doi.org/10.1021/acssensors.0c01553S2966297259World drug report United Nations Office on Drugs and Crime (UNODC). Inform; 2019.European drug report Trends and Developments. European Monitoring Centre for Drugs and Drug Addition (EMCDDA). Inform; 2019.Zawilska, J. B., & Wojcieszak, J. (2013). Designer cathinones—An emerging class of novel recreational drugs. Forensic Science International, 231(1-3), 42-53. doi:10.1016/j.forsciint.2013.04.015Coppola, M., & Mondola, R. (2012). 3,4-Methylenedioxypyrovalerone (MDPV): Chemistry, pharmacology and toxicology of a new designer drug of abuse marketed online. Toxicology Letters, 208(1), 12-15. doi:10.1016/j.toxlet.2011.10.002Coppola, M., & Mondola, R. (2012). Synthetic cathinones: Chemistry, pharmacology and toxicology of a new class of designer drugs of abuse marketed as «bath salts» or «plant food». Toxicology Letters, 211(2), 144-149. doi:10.1016/j.toxlet.2012.03.009Oliver, C. F., Palamar, J. J., Salomone, A., Simmons, S. J., Philogene-Khalid, H. L., Stokes-McCloskey, N., & Rawls, S. M. (2018). Synthetic cathinone adulteration of illegal drugs. Psychopharmacology, 236(3), 869-879. doi:10.1007/s00213-018-5066-6Riley, A. L., Nelson, K. H., To, P., López-Arnau, R., Xu, P., Wang, D., … Hall, F. S. (2020). Abuse potential and toxicity of the synthetic cathinones (i.e., «Bath salts»). Neuroscience & Biobehavioral Reviews, 110, 150-173. doi:10.1016/j.neubiorev.2018.07.015Ibáñez, M., Pozo, Ó. J., Sancho, J. V., Orengo, T., Haro, G., & Hernández, F. (2015). Analytical strategy to investigate 3,4-methylenedioxypyrovalerone (MDPV) metabolites in consumers’ urine by high-resolution mass spectrometry. Analytical and Bioanalytical Chemistry, 408(1), 151-164. doi:10.1007/s00216-015-9088-1Colon-Perez, L. M., Pino, J. A., Saha, K., Pompilus, M., Kaplitz, S., Choudhury, N., … Febo, M. (2018). Functional connectivity, behavioral and dopaminergic alterations 24 hours following acute exposure to synthetic bath salt drug methylenedioxypyrovalerone. Neuropharmacology, 137, 178-193. doi:10.1016/j.neuropharm.2018.04.031Eshleman, A. J., Nagarajan, S., Wolfrum, K. M., Reed, J. F., Swanson, T. L., Nilsen, A., & Janowsky, A. (2018). Structure-activity relationships of bath salt components: substituted cathinones and benzofurans at biogenic amine transporters. Psychopharmacology, 236(3), 939-952. doi:10.1007/s00213-018-5059-5Glennon, R. A., & Young, R. (2016). Neurobiology of 3,4-methylenedioxypyrovalerone (MDPV) and α-pyrrolidinovalerophenone (α-PVP). Brain Research Bulletin, 126, 111-126. doi:10.1016/j.brainresbull.2016.04.011Kraemer, M., Boehmer, A., Madea, B., & Maas, A. (2019). Death cases involving certain new psychoactive substances: A review of the literature. Forensic Science International, 298, 186-267. doi:10.1016/j.forsciint.2019.02.021Liveri, K., Constantinou, M. A., Afxentiou, M., & Kanari, P. (2016). A fatal intoxication related to MDPV and pentedrone combined with antipsychotic and antidepressant substances in Cyprus. Forensic Science International, 265, 160-165. doi:10.1016/j.forsciint.2016.02.017Marinetti, L. J., & Antonides, H. M. (2013). Analysis of Synthetic Cathinones Commonly Found in Bath Salts in Human Performance and Postmortem Toxicology: Method Development, Drug Distribution and Interpretation of Results. Journal of Analytical Toxicology, 37(3), 135-146. doi:10.1093/jat/bks136Freni, F., Bianco, S., Vignali, C., Groppi, A., Moretti, M., Osculati, A. M. M., & Morini, L. (2019). A multi-analyte LC–MS/MS method for screening and quantification of 16 synthetic cathinones in hair: Application to postmortem cases. Forensic Science International, 298, 115-120. doi:10.1016/j.forsciint.2019.02.036Peiró, M. de las N., Armenta, S., Garrigues, S., & de la Guardia, M. (2016). Determination of 3,4-methylenedioxypyrovalerone (MDPV) in oral and nasal fluids by ion mobility spectrometry. Analytical and Bioanalytical Chemistry, 408(12), 3265-3273. doi:10.1007/s00216-016-9395-1Cheng, S.-Y., Ng-A-Qui, T., Eng, B., & Ho, J. (2017). Detection of cathinone and mephedrone in plasma by LC-MS/MS using standard addition quantification technique. Journal of Analytical Science and Technology, 8(1). doi:10.1186/s40543-017-0128-7Glicksberg, L., Bryand, K., & Kerrigan, S. (2016). Identification and quantification of synthetic cathinones in blood and urine using liquid chromatography-quadrupole/time of flight (LC-Q/TOF) mass spectrometry. Journal of Chromatography B, 1035, 91-103. doi:10.1016/j.jchromb.2016.09.027Mercieca, G., Odoardi, S., Cassar, M., & Strano Rossi, S. (2018). Rapid and simple procedure for the determination of cathinones, amphetamine-like stimulants and other new psychoactive substances in blood and urine by GC–MS. Journal of Pharmaceutical and Biomedical Analysis, 149, 494-501. doi:10.1016/j.jpba.2017.11.024Gerace, E., Caneparo, D., Borio, F., Salomone, A., & Vincenti, M. (2019). Determination of several synthetic cathinones and an amphetamine‐like compound in urine by gas chromatography with mass spectrometry. Method validation and application to real cases. Journal of Separation Science, 42(8), 1577-1584. doi:10.1002/jssc.201801249Woźniak, M. K., Banaszkiewicz, L., Wiergowski, M., Tomczak, E., Kata, M., Szpiech, B., … Biziuk, M. (2019). Development and validation of a GC–MS/MS method for the determination of 11 amphetamines and 34 synthetic cathinones in whole blood. Forensic Toxicology, 38(1), 42-58. doi:10.1007/s11419-019-00485-yJoshi, M., Cetroni, B., Camacho, A., Krueger, C., & Midey, A. J. (2014). Analysis of synthetic cathinones and associated psychoactive substances by ion mobility spectrometry. Forensic Science International, 244, 196-206. doi:10.1016/j.forsciint.2014.08.033Peters, J. R., Keasling, R., Brown, S. D., & Pond, B. B. (2016). Quantification of Synthetic Cathinones in Rat Brain Using HILIC–ESI-MS/MS. Journal of Analytical Toxicology. doi:10.1093/jat/bkw074Williams, M., Martin, J., & Galettis, P. (2017). A Validated Method for the Detection of 32 Bath Salts in Oral Fluid. Journal of Analytical Toxicology, 41(8), 659-669. doi:10.1093/jat/bkx055Diestelmann, M., Zangl, A., Herrle, I., Koch, E., Graw, M., & Paul, L. D. (2018). MDPV in forensic routine cases: Psychotic and aggressive behavior in relation to plasma concentrations. Forensic Science International, 283, 72-84. doi:10.1016/j.forsciint.2017.12.003Garrido, E., Pla, L., Lozano-Torres, B., El Sayed, S., Martínez-Máñez, R., & Sancenón, F. (2018). Chromogenic and Fluorogenic Probes for the Detection of Illicit Drugs. ChemistryOpen, 7(5), 401-428. doi:10.1002/open.201800034García‐Fernández, A., Aznar, E., Martínez‐Máñez, R., & Sancenón, F. (2019). New Advances in In Vivo Applications of Gated Mesoporous Silica as Drug Delivery Nanocarriers. Small, 16(3), 1902242. doi:10.1002/smll.201902242Llopis-Lorente, A., Lozano-Torres, B., Bernardos, A., Martínez-Máñez, R., & Sancenón, F. (2017). Mesoporous silica materials for controlled delivery based on enzymes. Journal of Materials Chemistry B, 5(17), 3069-3083. doi:10.1039/c7tb00348jGiménez, C., Climent, E., Aznar, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., … Rurack, K. (2014). Towards Chemical Communication between Gated Nanoparticles. Angewandte Chemie International Edition, n/a-n/a. doi:10.1002/anie.201405580Luis, B., Llopis‐Lorente, A., Rincón, P., Gadea, J., Sancenón, F., Aznar, E., … Martínez‐Máñez, R. (2019). An Interactive Model of Communication between Abiotic Nanodevices and Microorganisms. Angewandte Chemie International Edition, 58(42), 14986-14990. doi:10.1002/anie.201908867Garrido, E., Alfonso, M., Díaz de Greñu, B., Lozano‐Torres, B., Parra, M., Gaviña, P., … Sancenón, F. (2020). Nanosensor for Sensitive Detection of the New Psychedelic Drug 25I‐NBOMe. Chemistry – A European Journal, 26(13), 2813-2816. doi:10.1002/chem.201905688Ribes, À., Aznar, E., Santiago-Felipe, S., Xifre-Perez, E., Tormo-Mas, M. Á., Pemán, J., … Martínez-Máñez, R. (2019). Selective and Sensitive Probe Based in Oligonucleotide-Capped Nanoporous Alumina for the Rapid Screening of Infection Produced by Candida albicans. ACS Sensors, 4(5), 1291-1298. doi:10.1021/acssensors.9b00169Oroval, M., Coll, C., Bernardos, A., Marcos, M. D., Martínez-Máñez, R., Shchukin, D. G., & Sancenón, F. (2017). Selective Fluorogenic Sensing of As(III) Using Aptamer-Capped Nanomaterials. ACS Applied Materials & Interfaces, 9(13), 11332-11336. doi:10.1021/acsami.6b15164Aznar, E., Villalonga, R., Giménez, C., Sancenón, F., Marcos, M. D., Martínez-Máñez, R., … Amorós, P. (2013). Glucose-triggered release using enzyme-gated mesoporous silica nanoparticles. Chemical Communications, 49(57), 6391. doi:10.1039/c3cc42210kGiménez, C., Climent, E., Aznar, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., … Rurack, K. (2014). Towards Chemical Communication between Gated Nanoparticles. Angewandte Chemie International Edition, n/a-n/a. doi:10.1002/anie.201405580Maerten, C., Garnier, T., Lupattelli, P., Chau, N. T. T., Schaaf, P., Jierry, L., & Boulmedais, F. (2015). Morphogen Electrochemically Triggered Self-Construction of Polymeric Films Based on Mussel-Inspired Chemistry. Langmuir, 31(49), 13385-13393. doi:10.1021/acs.langmuir.5b03774Beck, J. S., Vartuli, J. C., Roth, W. J., Leonowicz, M. E., Kresge, C. T., Schmitt, K. D., … Schlenker, J. L. (1992). A new family of mesoporous molecular sieves prepared with liquid crystal templates. Journal of the American Chemical Society, 114(27), 10834-10843. doi:10.1021/ja00053a020Cai, Q., Luo, Z.-S., Pang, W.-Q., Fan, Y.-W., Chen, X.-H., & Cui, F.-Z. (2001). Dilute Solution Routes to Various Controllable Morphologies of MCM-41 Silica with a Basic Medium. Chemistry of Materials, 13(2), 258-263. doi:10.1021/cm990661zDebruyne, D., Loilier, M., Cesbron, A., Le Boisselier, R., & Bourgine, J. (2014). Emerging drugs of abuse: current perspectives on substituted cathinones. Substance Abuse and Rehabilitation, 37. doi:10.2147/sar.s37257Marusich, J. A., Antonazzo, K. R., Wiley, J. L., Blough, B. E., Partilla, J. S., & Baumann, M. H. (2014). Pharmacology of novel synthetic stimulants structurally related to the «bath salts» constituent 3,4-methylenedioxypyrovalerone (MDPV). Neuropharmacology, 87, 206-213. doi:10.1016/j.neuropharm.2014.02.016Baumann, M. H., Partilla, J. S., Lehner, K. R., Thorndike, E. B., Hoffman, A. F., Holy, M., … Schindler, C. W. (2012). Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts’ Products. Neuropsychopharmacology, 38(4), 552-562. doi:10.1038/npp.2012.20

Synthesis of Fluorogenic Arylureas and Amides and Their Interaction with Amines: A Competition between Turn-on Fluorescence and Organic Radicals on the Way to a Smart Label for Fish Freshness

We describe the synthesis of fluorogenic arylureas and amides and their interaction with primary or secondary amines under air and light in organic-aqueous mixtures to give rise to a new class of persistent organic radicals, described on the basis of their electron paramagnetic resonance (EPR), as well as UV–vis, fluorescence, NMR, and quantum mechanics calculations, and their prospective use as multi-signal reporters in a smart label for fish freshness.Funded by the NATO Science for Peace and Security Programme (Grant SPS G5536), the Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo (Grant BU263P18), and the Ministerio de Ciencia e Innovación (Grant PID2019-111215RB-100

Nanosensor for Sensitive Detection of the New Psychedelic Drug 25I-NBOMe

This is the peer reviewed version of the following article: E. Garrido, M. Alfonso, B. Díaz de Greñu, B. Lozano-Torres, M. Parra, P. Gaviña, M. D. Marcos, R. Martínez-Máñez, F. Sancenón, Chem. Eur. J. 2020, 26, 2813, which has been published in final form at https://doi.org/10.1002/chem.201905688. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] This work reports the synthesis, characterization, and sensing behavior of a hybrid nanodevice for the detection of the potent abuse drug 25I-NBOMe. The system is based on mesoporous silica nanoparticles, loaded with a fluorescent dye, functionalized with a serotonin derivative and capped with the 5-HT2A receptor antibody. In the presence of 25I-NBOMe the capping antibody is displaced, leading to pore opening and rhodamine B release. This delivery was ascribed to 5-HT2A receptor antibody detachment from the surface due to its stronger coordination with 25I-NBOMe present in the solution. The prepared nanodevice allowed the sensitive (limit of detection of 0.6 mm) and selective recognition of the 25I-NBOMe drug (cocaine, heroin, mescaline, lysergic acid diethylamide, MDMA, and morphine were unable to induce pore opening and rhodamine B release). This nanodevice acts as a highly sensitive and selective fluorometric probe for the 25I-NBOMe illicit drug in artificial saliva and in sweets.The authors thank the Spanish Government (projects RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE) and CTQ2017-87954-P) and the Generalitat Valencia (PROMETEO/2018/024) for support. E.G. is grateful to the Spanish MEC for her FPU grant. The authors also thank the Electron Microscopy Service at the UPV for support.Garrido-García, EM.; Alfonso-Navarro, M.; Díaz De Greñu-Puertas, B.; Lozano-Torres, B.; Parra Álvarez, M.; Gaviña, P.; Marcos Martínez, MD.... (2020). Nanosensor for Sensitive Detection of the New Psychedelic Drug 25I-NBOMe. Chemistry - A European Journal. 26(13):2813-2816. https://doi.org/10.1002/chem.201905688S281328162613World drug report. United Nations Office on Drugs and Crime (UNODC). Inform2018;European drug report: Trends and Developments. European Monitoring Centre for Drugs and Drug Addition (EMCDDA). Inform2018.Zuba, D., Sekuła, K., & Buczek, A. (2013). 25C-NBOMe – New potent hallucinogenic substance identified on the drug market. Forensic Science International, 227(1-3), 7-14. doi:10.1016/j.forsciint.2012.08.027Poklis, J. L., Raso, S. A., Alford, K. N., Poklis, A., & Peace, M. R. (2015). Analysis of 25I-NBOMe, 25B-NBOMe, 25C-NBOMe and Other Dimethoxyphenyl-N-[(2-Methoxyphenyl) Methyl]Ethanamine Derivatives on Blotter Paper. Journal of Analytical Toxicology, 39(8), 617-623. doi:10.1093/jat/bkv073Agenda item 4.19.Expert Committee on Drug Dependence. Thirty-sixth Meeting. Geneva 16–20 June2014(World Health Organization).Batisse, A., Taright, N., Chevallier, C., Marillier, M., & Djezzar, S. (2016). «Dual disorder with drugs»: Comparison of two French databases. European Psychiatry, 33(S1), S72-S72. doi:10.1016/j.eurpsy.2016.01.005Rickli, A., Luethi, D., Reinisch, J., Buchy, D., Hoener, M. C., & Liechti, M. E. (2015). Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs). Neuropharmacology, 99, 546-553. doi:10.1016/j.neuropharm.2015.08.034Lawn, W., Barratt, M., Williams, M., Horne, A., & Winstock, A. (2014). The NBOMe hallucinogenic drug series: Patterns of use, characteristics of users and self-reported effects in a large international sample. Journal of Psychopharmacology, 28(8), 780-788. doi:10.1177/0269881114523866Kueppers, V. B., & Cooke, C. T. (2015). 25I-NBOMe related death in Australia: A case report. Forensic Science International, 249, e15-e18. doi:10.1016/j.forsciint.2015.02.010Laskowski, L. K., Elbakoush, F., Calvo, J., Exantus-Bernard, G., Fong, J., Poklis, J. L., … Nelson, L. S. (2014). Evolution of the NBOMes: 25C- and 25B- Sold as 25I-NBOMe. Journal of Medical Toxicology, 11(2), 237-241. doi:10.1007/s13181-014-0445-9Shanks, K. G., Sozio, T., & Behonick, G. S. (2015). Fatal Intoxications with 25B-NBOMe and 25I-NBOMe in Indiana During 2014. Journal of Analytical Toxicology, 39(8), 602-606. doi:10.1093/jat/bkv058Da Cunha, K. F., Eberlin, M. N., & Costa, J. L. (2017). Development and validation of a sensitive LC–MS/MS method to analyze NBOMes in dried blood spots: evaluation of long-term stability. Forensic Toxicology, 36(1), 113-121. doi:10.1007/s11419-017-0391-8Caspar, A. T., Helfer, A. G., Michely, J. A., Auwärter, V., Brandt, S. D., Meyer, M. R., & Maurer, H. H. (2015). Studies on the metabolism and toxicological detection of the new psychoactive designer drug 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe) in human and rat urine using GC-MS, LC-MSn, and LC-HR-MS/MS. Analytical and Bioanalytical Chemistry, 407(22), 6697-6719. doi:10.1007/s00216-015-8828-6Andrade, A. F. B., Mamo, S. K., & Gonzalez-Rodriguez, J. (2017). Rapid Screening Method for New Psychoactive Substances of Forensic Interest: Electrochemistry and Analytical Determination of Phenethylamines Derivatives (NBOMe) via Cyclic and Differential Pulse Voltammetry. Analytical Chemistry, 89(3), 1445-1452. doi:10.1021/acs.analchem.6b02426Coelho Neto, J. (2015). Rapid detection of NBOME’s and other NPS on blotter papers by direct ATR-FTIR spectrometry. Forensic Science International, 252, 87-92. doi:10.1016/j.forsciint.2015.04.025Wu, X., Eriksson, C., Wohlfarth, A., Wallgren, J., Kronstrand, R., Josefsson, M., … Konradsson, P. (2017). Synthesis and identification of metabolite biomarkers of 25C-NBOMe and 25I-NBOMe. Tetrahedron, 73(45), 6393-6400. doi:10.1016/j.tet.2017.09.024Slowing, I. I., Vivero-Escoto, J. L., Trewyn, B. G., & Lin, V. S.-Y. (2010). Mesoporous silica nanoparticles: structural design and applications. Journal of Materials Chemistry, 20(37), 7924. doi:10.1039/c0jm00554aAznar, E., Coll, C., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Ruiz, E. (2009). Borate-Driven Gatelike Scaffolding Using Mesoporous Materials Functionalised with Saccharides. Chemistry - A European Journal, 15(28), 6877-6888. doi:10.1002/chem.200900090Ribes, À., Aznar, E., Santiago-Felipe, S., Xifre-Perez, E., Tormo-Mas, M. Á., Pemán, J., … Martínez-Máñez, R. (2019). Selective and Sensitive Probe Based in Oligonucleotide-Capped Nanoporous Alumina for the Rapid Screening of Infection Produced by Candida albicans. ACS Sensors, 4(5), 1291-1298. doi:10.1021/acssensors.9b00169Coll, C., Bernardos, A., Martínez-Máñez, R., & Sancenón, F. (2012). Gated Silica Mesoporous Supports for Controlled Release and Signaling Applications. Accounts of Chemical Research, 46(2), 339-349. doi:10.1021/ar3001469Sancenón, F., Pascual, L., Oroval, M., Aznar, E., & Martínez-Máñez, R. (2015). Gated Silica Mesoporous Materials in Sensing Applications. ChemistryOpen, 4(4), 418-437. doi:10.1002/open.201500053Aznar, E., Villalonga, R., Giménez, C., Sancenón, F., Marcos, M. D., Martínez-Máñez, R., … Amorós, P. (2013). Glucose-triggered release using enzyme-gated mesoporous silica nanoparticles. Chemical Communications, 49(57), 6391. doi:10.1039/c3cc42210kGiménez, C., de la Torre, C., Gorbe, M., Aznar, E., Sancenón, F., Murguía, J. R., … Amorós, P. (2015). Gated Mesoporous Silica Nanoparticles for the Controlled Delivery of Drugs in Cancer Cells. Langmuir, 31(12), 3753-3762. doi:10.1021/acs.langmuir.5b00139Beck, J. S., Vartuli, J. C., Roth, W. J., Leonowicz, M. E., Kresge, C. T., Schmitt, K. D., … Schlenker, J. L. (1992). A new family of mesoporous molecular sieves prepared with liquid crystal templates. Journal of the American Chemical Society, 114(27), 10834-10843. doi:10.1021/ja00053a020Stöber, W., Fink, A., & Bohn, E. (1968). Controlled growth of monodisperse silica spheres in the micron size range. Journal of Colloid and Interface Science, 26(1), 62-69. doi:10.1016/0021-9797(68)90272-5Meng, H., Liu, Y., Zhai, Y., & Lai, L. (2013). Optimization of 5-hydroxytryptamines as dual function inhibitors targeting phospholipase A2 and leukotriene A4 hydrolase. European Journal of Medicinal Chemistry, 59, 160-167. doi:10.1016/j.ejmech.2012.10.05

Antimicrobial activity of commercial calcium phosphate based materials functionalized with vanillin

[EN] Infections represent one of the most frequent causes of arthroplasty revision. Thus, design of new antimi-crobial scaffolds to reduce implant rejections, bone infections and associated medical costs is highlydesired. In recent years, essential oil components (EOCs) have merged as compounds with signi¿cantantimicrobial activity that can be attached to speci¿c surfaces to enhance and prolong their antimicrobialeffect. Herein calcium phosphate CaP regenerative materials have been coated with a vanillin derivativeto combine its original bone regeneration properties with antimicrobial action of EOCs. Materials in formof microparticles and blocks were prepared and fully characterized. Clonogenic viability tests demon-strated that low concentrations of material (10 mg/mL-1) resulted effective to kill 100% of E. coli DH5abacteria. Additionally, vanillin containing scaffolds did not display any toxic effect over cells, yet theypreserve the ability to express alkaline phosphatase (ALPL), collagen type 1, chaina1(COL1A1) and bonegamma-carboxyglutamic acid-containing protein or osteocalcin (BGLAP), which are genes typicallyexpressed by osteoblasts. These results demonstrate that commercially available scaffolds can be func-tionalized with EOCs, achieving antimicrobial activity and open up a new approach for the treatmentand prevention of infection.The authors thank the Spanish Government, Spain for projects MAT2015-64139-C04-01-R (MINECO/FEDER). Also, Generalitat Valenciana, Spain (project PROMETEOII/2014/047) is acknowledged for their support. L. P. thanks Universitat Politecnica de Valencia, Spain for her FPI and mobility grants. B.D. thanks to Ministerio de Economia, Ciencia y Competitividad, Spain for his Juan de la Cierva-Formation fellowship. The authors also thank the Electron Microscopy Service at the UPV for their support. The authors are grateful to IRCCS Rizzoli Orthopaedic Institute, Italy (funds 5 X 1000 year 2015, cod. 6879).Polo, L.; Díaz De Greñu-Puertas, B.; Della Bella, E.; Pagani, S.; Torricelli, P.; Vivancos, J.; Ruiz Rico, M.... (2018). Antimicrobial activity of commercial calcium phosphate based materials functionalized with vanillin. Acta Biomaterialia. 81:293-303. https://doi.org/10.1016/j.actbio.2018.09.033S2933038

Janus Gold Nanostars-Mesoporous Silica Nanoparticles for NIR-Light-Triggered Drug Delivery

"This is the peer reviewed version of the following article: Hernández Montoto, Andy, Antoni Llopis-Lorente, Mónica Gorbe, José M. Terrés, Roberto Cao Milán, Borja Díaz de Greñu, María Alfonso, et al. 2019. Janus Gold Nanostars Mesoporous Silica Nanoparticles for NIR-Light-Triggered Drug Delivery. Chemistry A European Journal 25 (36). Wiley: 8471 78. doi:10.1002/chem.201900750, which has been published in final form at https://doi.org/10.1002/chem.201900750. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] Janus gold nanostar-mesoporous silica nanoparticle (AuNSt-MSNP) nanodevices able to release an entrapped payload upon irradiation with near infrared (NIR) light were prepared and characterized. The AuNSt surface was functionalized with a thiolated photolabile molecule (5), whereas the mesoporous silica face was loaded with a model drug (doxorubicin) and capped with proton-responsive benzimidazole-beta-cyclodextrin supramolecular gatekeepers (N 1). Upon irradiation with NIR-light, the photolabile compound 5 photodissociated, resulting in the formation of succinic acid, which induced the opening of the gatekeeper and cargo delivery. In the overall mechanism, the gold surface acts as a photochemical transducer capable of transforming the NIR-light input into a chemical messenger (succinic acid) that opens the supramolecular nanovalve. The prepared hybrid nanoparticles were non-cytotoxic to HeLa cells, until they were irradiated with a NIR laser, which led to intracellular doxorubicin release and hyperthermia. This induced a remarkable reduction in HeLa cells viability.The authors gratefully acknowledge financial support from the Spanish Government [Projects MAT2015-64139-C4-1-R, AGL2015-70235-C2-2-R and SAF2017-84689-R (MINECO/AEI/FEDER, UE)], the Generalitat Valenciana (Project PROMETEO2018/024) and European Union (Erasmus Mundus Programme, Action 2, grant agreement number 2014-0870/001001). A.H. thanks the Erasmus Mundus Programme for his PhD scholarship through the EuroInkaNet project. A.L.-L. thanks "La Caixa" Banking Foundation for his PhD scholarship.Hernández-Montoto, A.; Llopis-Lorente, A.; Gorbe, M.; Terrés-Haro, JM.; Cao Milán, R.; Díaz De Greñu-Puertas, B.; Alfonso-Navarro, M.... (2019). Janus Gold Nanostars-Mesoporous Silica Nanoparticles for NIR-Light-Triggered Drug Delivery. Chemistry - A European Journal. 25(36):8471-8478. https://doi.org/10.1002/chem.201900750S847184782536Yang, P., Gai, S., & Lin, J. (2012). Functionalized mesoporous silica materials for controlled drug delivery. Chemical Society Reviews, 41(9), 3679. doi:10.1039/c2cs15308dSancenón, F., Pascual, L., Oroval, M., Aznar, E., & Martínez-Máñez, R. (2015). Gated Silica Mesoporous Materials in Sensing Applications. ChemistryOpen, 4(4), 418-437. doi:10.1002/open.201500053Giménez, C., Climent, E., Aznar, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., … Rurack, K. (2014). Towards Chemical Communication between Gated Nanoparticles. Angewandte Chemie International Edition, n/a-n/a. doi:10.1002/anie.201405580Giménez, C., Climent, E., Aznar, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., … Rurack, K. (2014). Über den chemischen Informationsaustausch zwischen gesteuerten Nanopartikeln. Angewandte Chemie, 126(46), 12838-12843. doi:10.1002/ange.201405580Llopis-Lorente, A., Díez, P., Sánchez, A., Marcos, M. D., Sancenón, F., Martínez-Ruiz, P., … Martínez-Máñez, R. (2017). Interactive models of communication at the nanoscale using nanoparticles that talk to one another. Nature Communications, 8(1). doi:10.1038/ncomms15511Song, N., & Yang, Y.-W. (2015). Molecular and supramolecular switches on mesoporous silica nanoparticles. Chemical Society Reviews, 44(11), 3474-3504. doi:10.1039/c5cs00243eAznar, E., Oroval, M., Pascual, L., Murguía, J. R., Martínez-Máñez, R., & Sancenón, F. (2016). Gated Materials for On-Command Release of Guest Molecules. Chemical Reviews, 116(2), 561-718. doi:10.1021/acs.chemrev.5b00456Koutsopoulos, S. (2012). Molecular fabrications of smart nanobiomaterials and applications in personalized medicine. Advanced Drug Delivery Reviews, 64(13), 1459-1476. doi:10.1016/j.addr.2012.08.002Bao, G., Mitragotri, S., & Tong, S. (2013). Multifunctional Nanoparticles for Drug Delivery and Molecular Imaging. Annual Review of Biomedical Engineering, 15(1), 253-282. doi:10.1146/annurev-bioeng-071812-152409Hernández Montoto, A., Montes, R., Samadi, A., Gorbe, M., Terrés, J. M., Cao-Milán, R., … Martínez-Máñez, R. (2018). Gold Nanostars Coated with Mesoporous Silica Are Effective and Nontoxic Photothermal Agents Capable of Gate Keeping and Laser-Induced Drug Release. ACS Applied Materials & Interfaces, 10(33), 27644-27656. doi:10.1021/acsami.8b08395De la Torre, C., Domínguez-Berrocal, L., Murguía, J. R., Marcos, M. D., Martínez-Máñez, R., Bravo, J., & Sancenón, F. (2018). ϵ -Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C 9h Peptide to Induce Apoptosis in Cancer Cells. Chemistry - A European Journal, 24(8), 1890-1897. doi:10.1002/chem.201704161Teruel, A. H., Pérez-Esteve, É., González-Álvarez, I., González-Álvarez, M., Costero, A. M., Ferri, D., … Sancenón, F. (2018). Smart gated magnetic silica mesoporous particles for targeted colon drug delivery: New approaches for inflammatory bowel diseases treatment. Journal of Controlled Release, 281, 58-69. doi:10.1016/j.jconrel.2018.05.007García-Fernández, A., García-Laínez, G., Ferrándiz, M. L., Aznar, E., Sancenón, F., Alcaraz, M. J., … Orzáez, M. (2017). Targeting inflammasome by the inhibition of caspase-1 activity using capped mesoporous silica nanoparticles. Journal of Controlled Release, 248, 60-70. doi:10.1016/j.jconrel.2017.01.002Rastogi, S. K., Anderson, H. E., Lamas, J., Barret, S., Cantu, T., Zauscher, S., … Betancourt, T. (2017). Enhanced Release of Molecules upon Ultraviolet (UV) Light Irradiation from Photoresponsive Hydrogels Prepared from Bifunctional Azobenzene and Four-Arm Poly(ethylene glycol). ACS Applied Materials & Interfaces, 10(36), 30071-30080. doi:10.1021/acsami.6b16183Martínez-Carmona, M., Lozano, D., Baeza, A., Colilla, M., & Vallet-Regí, M. (2017). A novel visible light responsive nanosystem for cancer treatment. Nanoscale, 9(41), 15967-15973. doi:10.1039/c7nr05050jWeissleder, R. (2001). A clearer vision for in vivo imaging. Nature Biotechnology, 19(4), 316-317. doi:10.1038/86684Jalani, G., Naccache, R., Rosenzweig, D. H., Haglund, L., Vetrone, F., & Cerruti, M. (2016). Photocleavable Hydrogel-Coated Upconverting Nanoparticles: A Multifunctional Theranostic Platform for NIR Imaging and On-Demand Macromolecular Delivery. Journal of the American Chemical Society, 138(3), 1078-1083. doi:10.1021/jacs.5b12357Yan, B., Boyer, J.-C., Branda, N. R., & Zhao, Y. (2011). Near-Infrared Light-Triggered Dissociation of Block Copolymer Micelles Using Upconverting Nanoparticles. Journal of the American Chemical Society, 133(49), 19714-19717. doi:10.1021/ja209793bKnežević, N. Ž., & Lin, V. S.-Y. (2013). A magnetic mesoporous silica nanoparticle-based drug delivery system for photosensitive cooperative treatment of cancer with a mesopore-capping agent and mesopore-loaded drug. Nanoscale, 5(4), 1544. doi:10.1039/c2nr33417hIbsen, S., Zahavy, E., Wrasdilo, W., Berns, M., Chan, M., & Esener, S. (2010). A Novel Doxorubicin Prodrug with Controllable Photolysis Activation for Cancer Chemotherapy. Pharmaceutical Research, 27(9), 1848-1860. doi:10.1007/s11095-010-0183-xPatchornik, A., Amit, B., & Woodward, R. B. (1970). Photosensitive protecting groups. Journal of the American Chemical Society, 92(21), 6333-6335. doi:10.1021/ja00724a041Amit, B., Zehavi, U., & Patchornik, A. (1974). Photosensitive protecting groups of amino sugars and their use in glycoside synthesis. 2-Nitrobenzyloxycarbonylamino and 6-nitroveratryloxycarbonylamino derivatives. The Journal of Organic Chemistry, 39(2), 192-196. doi:10.1021/jo00916a015Bai, X., Li, Z., Jockusch, S., Turro, N. J., & Ju, J. (2003). Photocleavage of a 2-nitrobenzyl linker bridging a fluorophore to the 5’ end of DNA. Proceedings of the National Academy of Sciences, 100(2), 409-413. doi:10.1073/pnas.242729099Laimgruber, S., Schreier, W. J., Schrader, T., Koller, F., Zinth, W., & Gilch, P. (2005). The Photochemistry ofo-Nitrobenzaldehyde as Seen by Femtosecond Vibrational Spectroscopy. Angewandte Chemie International Edition, 44(48), 7901-7904. doi:10.1002/anie.200501642Laimgruber, S., Schreier, W. J., Schrader, T., Koller, F., Zinth, W., & Gilch, P. (2005). Femtosekunden-Schwingungsspektroskopie der Photochemie vono-Nitrobenzaldehyd. Angewandte Chemie, 117(48), 8114-8118. doi:10.1002/ange.200501642Fomina, N., McFearin, C., Sermsakdi, M., Edigin, O., & Almutairi, A. (2010). UV and Near-IR Triggered Release from Polymeric Nanoparticles. Journal of the American Chemical Society, 132(28), 9540-9542. doi:10.1021/ja102595jLin, Q., Huang, Q., Li, C., Bao, C., Liu, Z., Li, F., & Zhu, L. (2010). Anticancer Drug Release from a Mesoporous Silica Based Nanophotocage Regulated by Either a One- or Two-Photon Process. Journal of the American Chemical Society, 132(31), 10645-10647. doi:10.1021/ja103415tAujard, I., Benbrahim, C., Gouget, M., Ruel, O., Baudin, J.-B., Neveu, P., & Jullien, L. (2006). o-Nitrobenzyl Photolabile Protecting Groups with Red-Shifted Absorption: Syntheses and Uncaging Cross-Sections for One- and Two-Photon Excitation. Chemistry - A European Journal, 12(26), 6865-6879. doi:10.1002/chem.200501393Zhao, J., Gover, T. D., Muralidharan, S., Auston, D. A., Weinreich, D., & Kao, J. P. Y. (2006). Caged Vanilloid Ligands for Activation of TRPV1 Receptors by 1- and 2-Photon Excitation†. Biochemistry, 45(15), 4915-4926. doi:10.1021/bi052082fCohanoschi, I., & Hernández, F. E. (2005). Surface Plasmon Enhancement of Two- and Three-Photon Absorption of Hoechst 33 258 Dye in Activated Gold Colloid Solution. The Journal of Physical Chemistry B, 109(30), 14506-14512. doi:10.1021/jp0508958Voliani, V., Ricci, F., Signore, G., Nifosì, R., Luin, S., & Beltram, F. (2011). Multiphoton Molecular Photorelease in Click-Chemistry-Functionalized Gold Nanoparticles. Small, 7(23), 3271-3275. doi:10.1002/smll.201101753Voliani, V., Signore, G., Vittorio, O., Faraci, P., Luin, S., Peréz-Prieto, J., & Beltram, F. (2013). Cancer phototherapy in living cells by multiphoton release of doxorubicin from gold nanospheres. Journal of Materials Chemistry B, 1(34), 4225. doi:10.1039/c3tb20798fLlopis-Lorente, A., de Luis, B., García-Fernández, A., Díez, P., Sánchez, A., Dolores Marcos, M., … Sancenón, F. (2017). Au–Mesoporous silica nanoparticles gated with disulfide-linked oligo(ethylene glycol) chains for tunable cargo delivery mediated by an integrated enzymatic control unit. Journal of Materials Chemistry B, 5(33), 6734-6739. doi:10.1039/c7tb02045gLlopis-Lorente, A., Díez, P., de la Torre, C., Sánchez, A., Sancenón, F., Aznar, E., … Villalonga, R. (2017). Enzyme-Controlled Nanodevice for Acetylcholine-Triggered Cargo Delivery Based on Janus Au-Mesoporous Silica Nanoparticles. Chemistry - A European Journal, 23(18), 4276-4281. doi:10.1002/chem.201700603Llopis-Lorente, A., de Luis, B., García-Fernández, A., Jimenez-Falcao, S., Orzáez, M., Sancenón, F., … Martínez-Máñez, R. (2018). Hybrid Mesoporous Nanocarriers Act by Processing Logic Tasks: Toward the Design of Nanobots Capable of Reading Information from the Environment. ACS Applied Materials & Interfaces, 10(31), 26494-26500. doi:10.1021/acsami.8b05920Trigari, S., Rindi, A., Margheri, G., Sottini, S., Dellepiane, G., & Giorgetti, E. (2011). Synthesis and modelling of gold nanostars with tunable morphology and extinction spectrum. Journal of Materials Chemistry, 21(18), 6531. doi:10.1039/c0jm04519eSenthil Kumar, P., Pastoriza-Santos, I., Rodríguez-González, B., Javier García de Abajo, F., & Liz-Marzán, L. M. (2007). High-yield synthesis and optical response of gold nanostars. Nanotechnology, 19(1), 015606. doi:10.1088/0957-4484/19/01/015606Guerrero-Martínez, A., Barbosa, S., Pastoriza-Santos, I., & Liz-Marzán, L. M. (2011). Nanostars shine bright for you. Current Opinion in Colloid & Interface Science, 16(2), 118-127. doi:10.1016/j.cocis.2010.12.007Hao, F., Nehl, C. L., Hafner, J. H., & Nordlander, P. (2007). Plasmon Resonances of a Gold Nanostar. Nano Letters, 7(3), 729-732. doi:10.1021/nl062969cAznar, E., Villalonga, R., Giménez, C., Sancenón, F., Marcos, M. D., Martínez-Máñez, R., … Amorós, P. (2013). Glucose-triggered release using enzyme-gated mesoporous silica nanoparticles. Chemical Communications, 49(57), 6391. doi:10.1039/c3cc42210kAznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., Amorós, P., & Guillem, C. (2009). pH- and Photo-Switched Release of Guest Molecules from Mesoporous Silica Supports. Journal of the American Chemical Society, 131(19), 6833-6843. doi:10.1021/ja810011pKlán, P., Šolomek, T., Bochet, C. G., Blanc, A., Givens, R., Rubina, M., … Wirz, J. (2012). Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy. Chemical Reviews, 113(1), 119-191. doi:10.1021/cr300177kRittikulsittichai, S., Park, C. S., Marquez, M. D., Jamison, A. C., Frank, T., Wu, C.-H., … Lee, T. R. (2018). Inhibiting Reductive Elimination as an Intramolecular Disulfide Dramatically Enhances the Thermal Stability of SAMs on Gold Derived from Bidentate Adsorbents. Langmuir, 34(23), 6645-6652. doi:10.1021/acs.langmuir.7b0397

Role of Seroalbumin in the Cytotoxicity of cis-Dichloro Pt(II) Complexes with (N^N)-Donor Ligands Bearing Functionalized Tails

Given the potent anticancer properties of cisdiamminedichloroplatinum( II) and knowing its mode of action, we synthesized four new cis-[PtCl2(N^N)] organoplatinum complexes, two with N-substituted pbi ligands (pbiR = 1-R-2-(2-pyridyl)benzimidazole) (namely, 1 and 2) and two more with 4,4′-disubstituted bpy ligands (bpy = 2,2′-bipyridine) (namely, 3 and 4). We explored their cytotoxicity and ability to bind to deoxyguanosine monophosphate (dGMP), DNA, and albumin models. By 1H NMR and UV−vis spectroscopies, circular dichroism, agarose gel electrophoresis, differential scanning calorimetry measurements, and density functional theory calculations, we verified that only 3 can form aquacomplex species after dimethyl sulfoxide solvation; surprisingly, 1, 2, and 3 can bind covalently to DNA, whereas 4 can form a noncovalent complex. Interestingly, only complexes 1 and 4 exhibit good cytotoxicity against human ovarian carcinoma (HeLa) cell line, whereas 2 and 3 are inactive. Although lung carcinoma (A549) cells are more resistant to the four platinum complexes than HeLa cells, when the protein concentration in the extracellular media is lower, the cytotoxicity becomes substantially enhanced. By native electrophoresis of bovine seroalbumin (BSA) and inductively coupled plasma mass spectrometry uptake studies we bear out, on one hand, that 2 and 3 can interact strongly with BSA and its cellular uptake is negligible and, on the other hand, that 1 and 4 can interact with BSA only weakly, its cellular uptake being higher by several orders. These results point up the important role of the protein binding features on their biological activity and cellular uptake of cis-“PtCl2” derivatives. Our results are valuable in the future rational design of new platinum complexes with improved biological properties, as they expose the importance not only of their DNA binding abilities but also of additional factors such as protein binding.La Caixa Foundation (LCF/PR/PR12/11070003), Ministerio de Economía y Competitividad-FEDER (CTQ2014-58812-C2-2- R, CTQ2014-58812-C2-1-R, and CTQ2015-70371-REDT), Consejería de Educación−Junta de Castilla y León-FEDER (BU042U16), Spain

A Sensitive Nanosensor for the In Situ Detection of the Cannibal Drug

[EN] A bio-inspired nanodevice for the selective and sensitive fluorogenic detection of 3,4- methylenedioxypyrovalerone (MDPV), usually known as Cannibal drug, is reported. The sensing nanodevice is based on mesoporous silica nanoparticles (MSNs), loaded with a fluorescent reporter (rhodamine B) and functionalized on their external surface with a dopamine derivative (3), which specifically interacts with the recombinant human dopamine transporter (DAT), capping the pores. In the presence of MDPV, DAT detaches from the MSNs consequently causing rhodamine B release and allowing drug detection. The nanosensor shows a detection limit of 5.2 µM and it is able to detect the MDPV drug both in saliva and blood plasma samples.The authors thank the Spanish Government (projects RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE) and CTQ2017-87954-P) and the Generalitat Valencia (PROMETEO/2018/024) for support. E.G. is grateful to the Spanish MEC for her FPU grant. M.A. thanks her postdoctoral fellowship (PAID -10-17). The authors also thank the Electron Microscopy Service at the UPV for support.Garrido-García, EM.; Alfonso-Navarro, M.; Díaz De Greñu-Puertas, B.; Marcos Martínez, MD.; Costero, AM.; Gil Grau, S.; Sancenón Galarza, F.... (2020). A sensitive nanosensor for the in situ detection of the cannibal drug. ACS Sensors. 5(9):2966-2972. https://doi.org/10.1021/acssensors.0c015532966297259World drug report United Nations Office on Drugs and Crime (UNODC). Inform; 2019.European drug report Trends and Developments. European Monitoring Centre for Drugs and Drug Addition (EMCDDA). Inform; 2019.Zawilska, J. B., & Wojcieszak, J. (2013). Designer cathinones—An emerging class of novel recreational drugs. Forensic Science International, 231(1-3), 42-53. doi:10.1016/j.forsciint.2013.04.015Coppola, M., & Mondola, R. (2012). 3,4-Methylenedioxypyrovalerone (MDPV): Chemistry, pharmacology and toxicology of a new designer drug of abuse marketed online. Toxicology Letters, 208(1), 12-15. doi:10.1016/j.toxlet.2011.10.002Coppola, M., & Mondola, R. (2012). Synthetic cathinones: Chemistry, pharmacology and toxicology of a new class of designer drugs of abuse marketed as «bath salts» or «plant food». Toxicology Letters, 211(2), 144-149. doi:10.1016/j.toxlet.2012.03.009Oliver, C. F., Palamar, J. J., Salomone, A., Simmons, S. J., Philogene-Khalid, H. L., Stokes-McCloskey, N., & Rawls, S. M. (2018). Synthetic cathinone adulteration of illegal drugs. Psychopharmacology, 236(3), 869-879. doi:10.1007/s00213-018-5066-6Riley, A. L., Nelson, K. H., To, P., López-Arnau, R., Xu, P., Wang, D., … Hall, F. S. (2020). Abuse potential and toxicity of the synthetic cathinones (i.e., «Bath salts»). Neuroscience & Biobehavioral Reviews, 110, 150-173. doi:10.1016/j.neubiorev.2018.07.015Ibáñez, M., Pozo, Ó. J., Sancho, J. V., Orengo, T., Haro, G., & Hernández, F. (2015). Analytical strategy to investigate 3,4-methylenedioxypyrovalerone (MDPV) metabolites in consumers’ urine by high-resolution mass spectrometry. Analytical and Bioanalytical Chemistry, 408(1), 151-164. doi:10.1007/s00216-015-9088-1Colon-Perez, L. M., Pino, J. A., Saha, K., Pompilus, M., Kaplitz, S., Choudhury, N., … Febo, M. (2018). Functional connectivity, behavioral and dopaminergic alterations 24 hours following acute exposure to synthetic bath salt drug methylenedioxypyrovalerone. Neuropharmacology, 137, 178-193. doi:10.1016/j.neuropharm.2018.04.031Eshleman, A. J., Nagarajan, S., Wolfrum, K. M., Reed, J. F., Swanson, T. L., Nilsen, A., & Janowsky, A. (2018). Structure-activity relationships of bath salt components: substituted cathinones and benzofurans at biogenic amine transporters. Psychopharmacology, 236(3), 939-952. doi:10.1007/s00213-018-5059-5Glennon, R. A., & Young, R. (2016). Neurobiology of 3,4-methylenedioxypyrovalerone (MDPV) and α-pyrrolidinovalerophenone (α-PVP). Brain Research Bulletin, 126, 111-126. doi:10.1016/j.brainresbull.2016.04.011Kraemer, M., Boehmer, A., Madea, B., & Maas, A. (2019). Death cases involving certain new psychoactive substances: A review of the literature. Forensic Science International, 298, 186-267. doi:10.1016/j.forsciint.2019.02.021Liveri, K., Constantinou, M. A., Afxentiou, M., & Kanari, P. (2016). A fatal intoxication related to MDPV and pentedrone combined with antipsychotic and antidepressant substances in Cyprus. Forensic Science International, 265, 160-165. doi:10.1016/j.forsciint.2016.02.017Marinetti, L. J., & Antonides, H. M. (2013). Analysis of Synthetic Cathinones Commonly Found in Bath Salts in Human Performance and Postmortem Toxicology: Method Development, Drug Distribution and Interpretation of Results. Journal of Analytical Toxicology, 37(3), 135-146. doi:10.1093/jat/bks136Freni, F., Bianco, S., Vignali, C., Groppi, A., Moretti, M., Osculati, A. M. M., & Morini, L. (2019). A multi-analyte LC–MS/MS method for screening and quantification of 16 synthetic cathinones in hair: Application to postmortem cases. Forensic Science International, 298, 115-120. doi:10.1016/j.forsciint.2019.02.036Peiró, M. de las N., Armenta, S., Garrigues, S., & de la Guardia, M. (2016). Determination of 3,4-methylenedioxypyrovalerone (MDPV) in oral and nasal fluids by ion mobility spectrometry. Analytical and Bioanalytical Chemistry, 408(12), 3265-3273. doi:10.1007/s00216-016-9395-1Cheng, S.-Y., Ng-A-Qui, T., Eng, B., & Ho, J. (2017). Detection of cathinone and mephedrone in plasma by LC-MS/MS using standard addition quantification technique. Journal of Analytical Science and Technology, 8(1). doi:10.1186/s40543-017-0128-7Glicksberg, L., Bryand, K., & Kerrigan, S. (2016). Identification and quantification of synthetic cathinones in blood and urine using liquid chromatography-quadrupole/time of flight (LC-Q/TOF) mass spectrometry. 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Synthesis of a Tetracorannulene-perylenediimide That Acts as a Selective Receptor for C60 over C70

We report the use of a tetraborylated perylenediimide as starting material for the preparation of a tetracorannulene-perylenediimide that is able to bind up to two fullerene-C60 molecules by host–guest molecular recognition with preference over C70. Titration with fullerene-C60 is followed by a dramatic shift of the aromatic signals in 1H NMR and an initial increase in the fluorescence of the system. By this simple mechanism, fluorogenic sensing of fullerene-C60 is easily accomplished by an unprecedented fluorescent turn-on mechanism.Ministerio de Economı́a y Competitividad, Spain (Projects CTQ2013-41067-P, CTQ2015-71353-R, and PGC2018-099470-B-100) and Junta de Castilla y León, Consejerı́a de Educación y Cultura y Fondo Social Europeo (Project BU263P18)