In this study we explore the effect on the electrochemical signals in aqueous buffers of the presence of hydrophilic alkylhydroxy and carboxy groups on the carbon atoms of cobalta bis(dicarbollide) ions. The oxygen-containing exo-skeletal substituents of cobalta bis(dicarbollide) ions belong to the perspective building blocks that are considered for bioconjugation. Carbon substitution provides wider versatility and applicability in terms of the flexibility of possible chemical pathways. However, until recently, the electrochemistry of compounds substituted only on boron atoms could be studied, due to the unavailability of carbon-substituted congeners. In the present study, electrochemistry in aqueous phosphate buffers is considered along with the dependence of electrochemical response on pH and concentration. The compounds used show electrochemical signals around -1.3 and +1.1 V of similar or slightly higher intensities than in the parent cobalta bis(dicarbollide) ion. The signals at positive electrochemical potential correspond to irreversible oxidation of the boron cage (the C2B9 building block) and at negative potential correspond to the reversible redox process of (CoIII/CoII) at the central atom. Although the first signal is typically sharp and its potential can be altered by a number of substituents, the second signal is complex and is composed of three overlapping peaks. This signal shows sigmoidal character at higher concentrations and may be used as a diagnostic tool for aggregation in solution. Surprisingly enough, the observed effects of the site of substitution (boron or carbon) and between individual groups on the electrochemical response were insignificant. Therefore, the substitutions would preserve promising properties of the parent cage for redox labelling, but would not allow for the further tuning of signal position in the electrochemical window.

Department of Biophysical Chemistry and Molecular Oncology Institute of Biophysics of the Czech Academy of Sciences Královopolská 135 612 65 Brno Czech Republic

Department of Synthesis Institute of Inorganic Chemistry of the Czech Academy of Sciences Hlavní 1001 250 68 Řež Czech Republic

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Hawthorne M.F., Andrews T.D. Carborane analogues of cobalticinium ion. Chem. Commun. 1965;19:443–444. doi: 10.1039/c19650000443. DOI

Sivaev I.B., Bregadze V.I. Chemistry of cobalt bis(dicarbollides). A review. Collect. Czech. Chem. Commun. 1999;64:783–805. doi: 10.1135/cccc19990783. DOI

Dash B.P., Satapathy R., Swain B.R., Mahanta C.S., Jena B.B., Hosmane N.S. Cobalt bis(dicarbollide) anion and its derivatives. J. Organomet. Chem. 2017;849–850:170–194. doi: 10.1016/j.jorganchem.2017.04.006. DOI

Grimes R.N. Carboranes. 3rd ed. Academic Press Ltd-Elsevier Science Ltd.; London, UK: 2016. pp. 1–1041.

Saxena A.K., Hosmane N.S. Recent Advances in the Chemistry of Carborane Metal-Complexes Incorporating D-Block and F-Block Elements. Chem. Rev. 1993;93:1081–1124. doi: 10.1021/cr00019a011. PubMed DOI

Hawthorne M.F. Chemistry of polyhedral species derived from transition metals and carboranes. Accounts Chem. Res. 1968;1:281–288. doi: 10.1021/ar50009a004. DOI

Junqueira G.M.A. Remarkable aromaticity of cobalt bis(dicarbollide) derivatives: A NICS study. Theor. Chem. Acc. 2018;137:7. doi: 10.1007/s00214-018-2272-6. DOI

Gozzi M., Schwarze B., Hey-Hawkins E. Preparing (Metalla)carboranes for Nanomedicine. ChemMedChem. 2021;16:1533–1565. doi: 10.1002/cmdc.202000983. PubMed DOI PMC

Viñas C., Tarres M., Gonzalez-Cardoso P., Farras P., Bauduin P., Teixidor F. Surfactant behaviour of metallacarboranes. A study based on the electrolysis of water. Dalton Trans. 2014;43:5062–5068. doi: 10.1039/C3DT52825A. PubMed DOI

Plešek J. Potential Applications of the Boron Cluster Compounds. Chem. Rev. 1992;92:269–278. doi: 10.1021/cr00010a005. DOI

Fanfrlík J., Lepšík M., Horinek D., Havlas Z., Hobza P. Interaction of Carboranes with Biomolecules: Formation of Dihydrogen Bonds. ChemPhysChem. 2006;7:1100–1105. doi: 10.1002/cphc.200500648. PubMed DOI

Dubey R.D., Sarkar A., Shen Z.Y., Bregadze V.I., Sivaev I.B., Druzina A.A., Zhidkova O.B., Shmal’ko A.V., Kosenko I.D., Sreejyothi P., et al. Effects of Linkers on the Development of Liposomal Formulation of Cholesterol Conjugated Cobalt Bis(dicarbollides) J. Pharm. Sci. 2021;110:1365–1373. doi: 10.1016/j.xphs.2020.12.017. PubMed DOI

Bregadze V.I., Sivaev I.B., Dubey R.D., Semioshkin A., Shmal’ko A.V., Kosenko I.D., Lebedeva K.V., Mandal S., Sreejyothi P., Sarkar A., et al. Boron-Containing Lipids and Liposomes: New Conjugates of Cholesterol with Polyhedral Boron Hydrides. Chem.-Eur. J. 2020;26:13832–13841. doi: 10.1002/chem.201905083. PubMed DOI

Assaf K.I., Begaj B., Frank A., Nilam M., Mougharbel A.S., Kortz U., Nekvinda J., Grüner B., Gabel D., Nau W.M. High-Affinity Binding of Metallacarborane Cobalt Bis(dicarbollide) Anions to Cyclodextrins and Application to Membrane Translocation. J. Org. Chem. 2019;84:11790–11798. doi: 10.1021/acs.joc.9b01688. PubMed DOI

Verdia-Baguena C., Alcaraz A., Aguilella V.M., Cioran A.M., Tachikawa S., Nakamura H., Teixidor F., Vinas C. Amphiphilic COSAN and I2-COSAN crossing synthetic lipid membranes: Planar bilayers and liposomes. Chem. Commun. 2014;50:6700–6703. doi: 10.1039/c4cc01283f. PubMed DOI

Gruner B., Brynda J., Das V., Sicha V., Stepankova J., Nekvinda J., Holub J., Pospisilova K., Fabry M., Pachl P., et al. Metallacarborane Sulfamides: Unconventional, Specific, and Highly Selective Inhibitors of Carbonic Anhydrase IX. J. Med. Chem. 2019;62:9560–9575. doi: 10.1021/acs.jmedchem.9b00945. PubMed DOI

Grzelczak M.P., Danks S.P., Klipp R.C., Belic D., Zaulet A., Kunstmann-Olsen C., Bradley D.F., Tsukuda T., Vinas C., Teixidor F., et al. Ion Transport across Biological Membranes by Carborane-Capped Gold Nanoparticles. ACS Nano. 2017;11:12492–12499. doi: 10.1021/acsnano.7b06600. PubMed DOI PMC

Tarres M., Canetta E., Vinas C., Teixidor F., Harwood A.J. Imaging in living cells using nu B-H Raman spectroscopy: Monitoring COSAN uptake. Chem. Commun. 2014;50:3370–3372. doi: 10.1039/C3CC49658A. PubMed DOI

Gona K.B., Zaulet A., Gomez-Vallejo V., Teixidor F., Llop J., Vinas C. COSAN as a molecular imaging platform: Synthesis and “in vivo’’ imaging. Chem. Commun. 2014;50:11415–11417. doi: 10.1039/C4CC05058D. PubMed DOI

Teixidor C.V., Teixidor F., Harwood A.J. Cobaltabisdicarbollide-Based Synthetic Vesicles: From Biological Interaction to In Vivo Imaging. John Wiley & Sons Ltd.; Chichester, UK: 2018. pp. 159–173.

Zhu Y.H., Hosmane N.S. Advanced carboraneous materials. J. Organomet. Chem. 2017;849–850:286–292. doi: 10.1016/j.jorganchem.2017.02.020. DOI

Lesnikowski Z.J. Challenges and Opportunities for the Application of Boron Clusters in Drug Design. J. Med. Chem. 2016;59:7738–7758. doi: 10.1021/acs.jmedchem.5b01932. PubMed DOI

Issa F., Kassiou M., Rendina M. Boron in Drug Discovery: Carboranes as Uniquie Pharmacophores in Biologically Active Compounds. Chem. Rev. 2011;111:5701–5722. doi: 10.1021/cr2000866. PubMed DOI

Olejniczak A.B., Nawrot B., Lesnikowski Z.J. DNA Modified with Boron-Metal Cluster Complexes M(C2B9H11)(2) Synthesis, Properties, and Applications. Int. J. Mol. Sci. 2018;19:3501. doi: 10.3390/ijms19113501. PubMed DOI PMC

Cigler P., Kozisek M., Rezacova P., Brynda J., Otwinowski Z., Pokorna J., Plesek J., Gruner B., Doleckova-Maresova L., Masa M., et al. From nonpeptide toward noncarbon protease inhibitors: Metallacarboranes as specific and potent inhibitors of HIV protease. Proc. Natl. Acad. Sci. USA. 2005;102:15394–15399. doi: 10.1073/pnas.0507577102. PubMed DOI PMC

Kožíšek M., Cígler P., Lepšík M., Fanfrlík J., Řezáčová P., Brynda J., Pokorná J., Plešek J., Grüner B., Grantz-Šašková K., et al. Inorganic polyhedral metallacarborane inhibitors of HIV protease: A new approach to overcoming antiviral resistance. J. Med. Chem. 2008;59:4839–4843. doi: 10.1021/jm8002334. PubMed DOI

Řezáčová P., Pokorná J., Brynda J., Kožíšek M., Cígler P., Lepšík M., Fanfrlík J., Řezáč J., Šašková K.G., Sieglová I., et al. Design of HIV Protease Inhibitors Based on Inorganic Polyhedral Metallacarboranes. J. Med. Chem. 2009;52:7132–7141. doi: 10.1021/jm9011388. PubMed DOI

Gruner B., Kugler M., El Anwar S., Holub J., Nekvinda J., Bavol D., Ruzickova Z., Pospisilova K., Fabry M., Kral V., et al. Cobalt Bis(dicarbollide) Alkylsulfonamides: Potent and Highly Selective Inhibitors of Tumor Specific Carbonic Anhydrase IX. Chempluschem. 2021;86:352–363. doi: 10.1002/cplu.202000574. PubMed DOI

Kugler M., Nekvinda J., Holub J., El Anwar S., Das V., Šícha V., Pospíšilová K., Fábry M., Král V., Brynda J., et al. Inhibitors of CA IX Enzyme Based on Polyhedral Boron Compounds. ChemBioChem. 2021;22:2741–2761. doi: 10.1002/cbic.202100121. PubMed DOI

Fuentes I., Garcia-Mendiola T., Sato S., Pita M., Nakamura H., Lorenzo E., Teixidor F., Marques F., Viñas C. Metallacarboranes on the Road to Anticancer Therapies: Cellular Uptake, DNA Interaction, and Biological Evaluation of Cobaltabisdicarbollide COSAN (-) Chem.-Eur. J. 2018;24:17239–17254. doi: 10.1002/chem.201803178. PubMed DOI

Popova T., Zaulet A., Teixidor F., Alexandrova R., Vinas C. Investigations on antimicrobial activity of cobaltabisdicarbollides. J. Organomet. Chem. 2013;747:229–234. doi: 10.1016/j.jorganchem.2013.07.006. DOI

Vankova E., Lokocova K., Matatkova O., Krizova I., Masak J., Gruner B., Kaule P., Cermak J., Sicha V. Cobalt bis-dicarbollide and its ammonium derivatives are effective antimicrobial and antibiofilm agents. J. Organomet. Chem. 2019;899:8. doi: 10.1016/j.jorganchem.2019.120891. DOI

Swietnicki W., Goldeman W., Psurski M., Nasulewicz-Goldeman A., Boguszewska-Czubara A., Drab M., Sycz J., Goszczynski T.M. Metallacarborane Derivatives Effective against Pseudomonas aeruginosa and Yersinia enterocolitica. Int. J. Mol. Sci. 2021;22:6762. doi: 10.3390/ijms22136762. PubMed DOI PMC

Kvasnickova E., Masak J., Cejka J., Matatkova O., Sicha V. Preparation, characterization, and the selective antimicrobial activity of N-alkylammonium 8-diethyleneglycol cobalt bis-dicarbollide derivatives. J. Organomet. Chem. 2017;827:23–31. doi: 10.1016/j.jorganchem.2016.10.037. DOI

Fink K., Uchman M. Boron cluster compounds as new chemical leads for antimicrobial therapy. Coord. Chem. Rev. 2021;431:10. doi: 10.1016/j.ccr.2020.213684. DOI

Fuentes I., Pujols J., Vinas C., Ventura S., Teixidor F. Dual Binding Mode of Metallacarborane Produces a Robust Shield on Proteins. Chem.-Eur. J. 2019;25:12820–12829. doi: 10.1002/chem.201902796. PubMed DOI

Fink K., Boratynski J., Paprocka M., Goszczynski T.M. Metallacarboranes as a tool for enhancing the activity of therapeutic peptides. Ann. N. Y. Acad. Sci. 2019;1457:128–141. doi: 10.1111/nyas.14201. PubMed DOI

Goszczynski T.M., Fink K., Boratynski J. Icosahedral boron clusters as modifying entities for biomolecules. Expert Opin. Biol. Ther. 2018;18:205–213. doi: 10.1080/14712598.2018.1473369. PubMed DOI

Núñez R., Tarres M., Ferrer-Ugalde A., de Biani F.F., Teixidor F. Electrochemistry and Photoluminescence of Icosahedral Carboranes, Boranes, Metallacarboranes, and Their Derivatives. Chem. Rev. 2016;116:14307–14378. doi: 10.1021/acs.chemrev.6b00198. PubMed DOI

Kodr D., Yenice C.P., Simonova A., Saftic D.P., Pohl R., Sykorova V., Ortiz M., Havran L., Fojta M., Lesnikowski Z.J., et al. Carborane- or Metallacarborane-Linked Nucleotides for Redox Labeling. Orthogonal Multipotential Coding of all Four DNA Bases for Electrochemical Analysis and Sequencing. J. Am. Chem. Soc. 2021;143:7124–7134. doi: 10.1021/jacs.1c02222. PubMed DOI

Olejniczak A.B., Lesnikowski Z.J. Boron Clusters as Redox Labels for Nucleosides and Nucleic Acids. World Scientific Publ Co Pte Ltd.; Singapore: 2019. pp. 1–13.

Gonzμlez-Cardoso P., Stoica A.I., Farràs P., Pepiol A., Vinas C., Teixidor F. Additive Tuning of Redox Potential in Metallacarboranes by Sequential Halogen Substitution. Chem.-Eur. J. 2010;16:6660–6665. doi: 10.1002/chem.200902558. PubMed DOI

Rudakov A., Shirokii V.L., Knizhnikov V.A., Bazhanov A.V., Vecher E.I., Maier N.A., Potkin V.I., Ryabtsev A.N., Petrovskii P.V., Sivaev I.B., et al. Electrochemical synthesis of halogen derivatives of bis(1,2-dicarbollyl)cobalt(III) Russ. Chem. Bull. Int. Ed. 2004;53:2554–2557. doi: 10.1007/s11172-005-0153-3. DOI

Fojt L., Gruner B., Sicha V., Nekvinda J., Vespalec R., Fojta M. Electrochemistry of icosahedral cobalt bis(dicarbollide) ions and their carbon and boron substituted derivatives in aqueous phosphate buffers. Electrochim. Acta. 2020;342:11. doi: 10.1016/j.electacta.2020.136112. DOI

Ziolkowski R., Olejniczak A.B., Gorski L., Janusik J., Lesnikowski Z.J., Malinowska E. Electrochemical detection of DNA hybridization using metallacarborane unit. Bioelectrochemistry. 2012;87:78–83. doi: 10.1016/j.bioelechem.2011.10.005. PubMed DOI

Palecek E., Bartosik M. Electrochemistry of Nucleic Acids. Chem. Rev. 2012;112:3427–3481. doi: 10.1021/cr200303p. PubMed DOI

Semioshkin A.A., Sivaev I.B., Bregadze V.I. Cyclic oxonium derivatives of polyhedral boron hydrides and their synthetic applications. Dalton Trans. 2008;2008:977–992. doi: 10.1039/b715363e. PubMed DOI

Selucky P., Plesek J., Rais J., Kyrs M., Kadlecova L. Extraction of Fission-Products into Nitrobenzene with Dicobalt Tris-Dicarbollide and Ethyleneoxy-Substituted Cobalt Bis- Dicarbollide. J. Radioanal. Nucl. Chem.-Artic. 1991;149:131–140. doi: 10.1007/BF02053721. DOI

Zaulet A., Teixidor F., Bauduin P., Diat O., Hirva P., Ofori A., Vinas C. Deciphering the role of the cation in anionic cobaltabisdicarbollide clusters. J. Organomet. Chem. 2018;865:214–225. doi: 10.1016/j.jorganchem.2018.03.023. DOI

Olejniczak A.B., Milecki J., Schroeder G. The Effect of Stereochemistry on Sodium Ion Complexation in Nucleoside-Metallacarborane Conjugates. Bioinorg. Chem. Appl. 2010;2010:196064. doi: 10.1155/2010/196064. PubMed DOI PMC

Dorďovic V., Tošner Z., Uchman M., Zhigunov A., Reza M., Ruokolainen J., Pramanik G., Cígler P., Kalikova K., Gradzielski M., et al. Stealth Amphiphiles: Self-Assembly of Polyhedral Boron Clusters. Langmuir. 2016;32:6713–6722. doi: 10.1021/acs.langmuir.6b01995. PubMed DOI

Grüner B., Švec P., Šícha V., Padĕlková Z. Direct and facile synthesis of carbon substituted alkylhydroxy derivatives of cobalt bis(1,2-dicarbollide), versatile building blocks for synthetic purposes. Dalton Trans. 2012;41:7498–7512. doi: 10.1039/c2dt30128h. PubMed DOI

Nekvinda J., Sicha V., Hnyk D., Gruner B. Synthesis, characterisation and some chemistry of C- and B-substituted carboxylic acids of cobalt bis(dicarbollide) Dalton Trans. 2014;43:5106–5120. doi: 10.1039/c3dt52870g. PubMed DOI

Scholz M., Hey-Hawkins E. Carbaboranes as Pharmacophores: Properties, Synthesis, and Application Strategies. Chem. Rev. 2011;111:7035–7062. doi: 10.1021/cr200038x. PubMed DOI

Fojt L., Fojta M., Grüner B., Vespalec R. Electrochemistry of closo-dodecaborate dianion and its simple exo-skeletal derivatives at carbon electrodes in aqueous phosphate buffers. J. Electroanal. Chem. 2013;707:38–42. doi: 10.1016/j.jelechem.2013.08.016. DOI

Fojt L., Fojta M., Gruner B., Vespalec R. Electrochemistry of parent and exo-skeletally substituted icosahedral monocarba and dicarbaboranes and their derivatives at the graphite carbon electrode in aqueous phosphate buffers. J. Electroanal. Chem. 2014;730:16–19. doi: 10.1016/j.jelechem.2014.07.023. DOI

Fojt L., Nekvinda J., El Anwar S., Gruner B., Havran L., Fojta M. Simple Electrochemical Characterization of ortho-carborane and Some of its Exo-skeletal Derivatives. Electroanalysis. 2020;32:1859–1866. doi: 10.1002/elan.202060038. DOI

Fojt L., Grüner B., Holub J., Havran L., Fojta M. Electrochemistry of icosahedral metal full and half sandwich metallacarboranes in phosphate buffers. J. Electroanal. Chem. 2022;910:116165. doi: 10.1016/j.jelechem.2022.116165. DOI

Plešek J., Grüner B., Šícha V., Bőhmer V., Císařová I. [(8,8′-μ-CH2O(CH3)-(1,2-C2B9H10)2-3,3′-Co]0 zwitterion as a versatile building block for introduction of the cobalt bis(dicarbollide) ion into organic molecules. Organometallics. 2012;31:1703–1715. doi: 10.1021/om200938n. DOI

Dong Y., Liu D., Yang Z. A brief review of methods for terminal functionalization of DNA. Methods. 2014;67:116. doi: 10.1016/j.ymeth.2013.11.004. PubMed DOI

Bühl M., Hnyk D., Macháček J. Computational study of structures and properties of metallaboranes: Cobalt bis(dicarbollide) Chem.-Eur. J. 2005;11:4109–4120. doi: 10.1002/chem.200401202. PubMed DOI

El Anwar S., Pazderová L., Bavol D., Bakardjiev M., Růžičková Z., Horáček O., Fojt L., Kučera R., Grűner B. Structurally rigidified cobalt bis(dicarbollide) derivatives, a chiral platform for labelling of biomolecules and new materials. Chem. Commun. 2022;58:2572–2575. doi: 10.1039/D1CC06979A. PubMed DOI

Bednarska-Szczepaniak K., Dziedzic-Kocurek K., Przelazly E., Stanek J., Lesnikowski Z.J. Intramolecular rotations and electronic states of iron in the iron bis(dicarbollide) complex Fe (C2B9H11)(2) studied by a Fe-57 nuclear probe and computational methods. Chem. Commun. 2022;58:391–394. doi: 10.1039/D1CC05111C. PubMed DOI

Chemistry of Carbon-Substituted Derivatives of Cobalt Bis(dicarbollide)(1-) Ion and Recent Progress in Boron Substitution