A set of substituted 1,4,7-triazacyclononane ligands was synthesised, including a wide series of novel derivatives bearing a thiazole or thiophene side group, with the potential to incorporate these derivatives into a polymeric material; some previously known/studied ligands were also synthesised for comparative purposes. The corresponding copper(II) complexes were prepared, and their ability to mediate the hydrolysis of phosphate ester bonds was studied via UV-Vis spectrophotometry, using bis(p-nitrophenyl)phosphate as a model substrate. Some of the prepared complexes showed a considerable enhancement of the phosphate ester hydrolysis in comparison with previously studied systems, which makes them some of the most effective complexes ever tested for this purpose. Therefore, these novel, potentially bifunctional systems could provide the possibility of creating new coating materials for medicinal devices that could prevent biofilm formation.

Department of Inorganic Chemistry Charles University Hlavova 2030 128 40 Prague Czech Republic

Zobrazit více v PubMed

Khatoon Z., McTiernan C.D., Suuronen E.J., Mah T.-F., Alarcon E.I. Bacterial biofilm formation on implantable devices and approaches to its treatment and prevention. Heliyon. 2018;4:e01067. doi: 10.1016/j.heliyon.2018.e01067. PubMed DOI PMC

Hegg E.L., Burstyn J.N. Toward the development of metal-based synthetic nucleases and peptidases: A rationale and progress report in applying the principles of coordination chemistry. Coord. Chem. Rev. 1998;173:133–165. doi: 10.1016/S0010-8545(98)00157-X. DOI

Desbouis D., Troitsky I.P., Belousoff M.J., Spiccia L., Graham B. Coper(II), zinc(II) and nickel(II) complexes as nuclease mimetics. Coord. Chem. Rev. 2012;256:897–937. doi: 10.1016/j.ccr.2011.12.005. DOI

Kumar P., Tomar S., Kumar K., Kumar S. Transition metal complexes as self-activating chemical nucleases: Proficient DNA cleavage without any exogenous redox agents. Dalton Trans. 2023;52:6961–6977. doi: 10.1039/D3DT00368J. PubMed DOI

Connolly J.A., Kim J.H., Banaszczyk M., Drouin M., Chin J. Factors affecting chelation of carboxylates to cis-diaqua Co(III) complexes: Implications on the reactivity of the metal complexes for hydrolyzing esters, amides, nitriles, and phosphates. Inorg. Chem. 1995;34:1094–1099. doi: 10.1021/ic00109a016. DOI

Burstyn J.N., Deal K.A. Selective catalytic hydrolysis of a simple phosphodiester by a macrocyclic copper(II) complex. Inorg. Chem. 1993;32:3585–3586. doi: 10.1021/ic00069a005. DOI

Hegg E.L., Mortimore S.H., Cheung C.L., Huyett J.E., Powell D.R., Burstyn J.N. Structure-reactivity studies in copper(II)-catalyzed phosphodiester hydrolysis. Inorg. Chem. 1999;38:2961–2968. doi: 10.1021/ic981087g. PubMed DOI

Zompa L.J. Metal complexes of cyclic triamines. 2. Stability and electronic spectra of nickel(II), copper(II), and zinc(II) complexes containing nine- through twelve-membered cyclic triamine ligands. Inorg. Chem. 1978;17:2531–2536. doi: 10.1021/ic50187a039. DOI

NIST Standard Reference Database 46 (Critically Selected Stability Constants of Metal Complexes) National Institute of Standards and Technology; Gaithersburg, MD, USA: 2003. Version 7.0.

Kubíček V., Böhmová Z., Ševčíková R., Vaněk J., Lubal P., Poláková Z., Michalicová R., Kotek J., Hermann P. NOTA complexes with copper(II) and divalent metal ions: Kinetic and thermodynamic studies. Inorg. Chem. 2018;57:3061–3072. doi: 10.1021/acs.inorgchem.7b02929. PubMed DOI

Deal K.A., Burstyn J.N. Mechanistic studies of dichloro(1,4,7-triazacyclononane)copper(II)-catalyzed phosphate diester hydrolysis. Inorg. Chem. 1996;35:2792–2798. doi: 10.1021/ic951488l. DOI

Deck K.M., Tseng T.A., Burstyn J.N. Triisopropyltriazacyclononane copper(II): An efficient phosphodiester hydrolysis catalyst and DNA cleavage agent. Inorg. Chem. 2002;41:669–677. doi: 10.1021/ic0107025. PubMed DOI

Fry F.H., Fischmann A.J., Belousoff M.J., Spiccia L., Brügger J. Kinetics and mechanism of hydrolysis of a model phosphate diester by [Cu(Me3tacn)(OH2)2]2+ (Me3tacn = 1,4,7-trimethyl-1,4,7-triazacyclononane) Inorg. Chem. 2005;44:941–950. doi: 10.1021/ic049469b. PubMed DOI

Belousoff M.J., Duriska M.B., Graham B., Batten S.R., Moubaraki B., Murray K.S., Spiccia L. Synthesis, X-ray crystal structures, magnetism, and phosphate ester cleavage properties of copper(II) complexes of N-substituted derivatives of 1,4,7-triazacyclononane. Inorg. Chem. 2006;45:3746–3755. doi: 10.1021/ic051983+. PubMed DOI

Belousoff M.J., Battle A.R., Graham B., Spiccia L. Syntheses, structures and hydrolytic properties of copper(II) complexes of asymmetrically N-functionalised 1,4,7-triazacyclononane ligands. Polyhedron. 2007;26:344–355. doi: 10.1016/j.poly.2006.06.029. DOI

Belousoff M.J., Tjioe L., Graham B., Spiccia L. Synthesis, X-ray crystal structures, and phosphate ester cleavage properties of bis(2-pyridylmethyl)amine copper(II) complexes with guanidinium pendant groups. Inorg. Chem. 2011;50:621–635. doi: 10.1021/ic8004079. PubMed DOI

Kirchmeyer S., Reuter K. Scientific importance, properties and growing applications of poly(3,4-ethylenedioxythiophene) J. Matter. Chem. 2005;15:2077–2088. doi: 10.1039/b417803n. DOI

Kaur G., Adhikari R., Cass P., Bown M., Gunatillake P. Electrically conductive polymers and composites for biomedical applications. RSC Adv. 2015;5:37553–37567. doi: 10.1039/C5RA01851J. DOI

Hegg E.L., Burstyn J.N. Copper(II) macrocycles cleave single-stranded and double-stranded DNA under both aerobic and anaerobic conditions. Inorg. Chem. 1996;35:7474–7481. doi: 10.1021/ic960384n. DOI

Patinec V., Rolla G.A., Botta M., Tripier R., Esteban-Gomez D., Platas-Iglesias C. Hyperfine coupling constants on inner-sphere water molecules of a triazacyclononane-based Mn(II) complex and related systems relevant as MRI contrast agents. Inorg. Chem. 2013;52:11173–11184. doi: 10.1021/ic4014366. PubMed DOI

Holub J., Meckel M., Kubíček V., Rösch F., Hermann P. Gallium(III) complexes of NOTA-bis(phosphonate) conjugates as PET radiotracers for bone imaging. Contrast Media Mol. Imaging. 2014;10:122–134. doi: 10.1002/cmmi.1606. PubMed DOI

Armarego W.L.F., Chai C.L.L. Purification of Laboratory Chemicals. 5th ed. Elsevier Science; Philadelphia, PA, USA: 2003.

Kotková Z., Koucký F., Kotek J., Císařová I., Parker D., Hermann P. Copper(II) complexes of cyclams with N-(2,2,2-trifluoroethyl)-aminoalkyl pendant arms as potential probes for 19F magnetic resonance imaging. Dalton Trans. 2023;52:1861–1875. doi: 10.1039/D2DT03360G. PubMed DOI

Benniston A.C., Gunning P., Peacock R.D. Synthesis and binding properties of hybrid cyclophane-azamacrocyclic receptors. J. Org. Chem. 2005;70:115–123. doi: 10.1021/jo048621o. PubMed DOI

Kumar S., Pearson A.L., Pratt R.F. Design, synthesis, and evaluation of α-ketoheterocycles as class C β-lactamase inhibitors. Bioorg. Med. Chem. 2001;9:2035–2044. doi: 10.1016/S0968-0896(01)00107-9. PubMed DOI

He L.-Y., Urrego-Riveros S., Gates P.J., Näther C., Brinkmann M., Abetz V., Staubitz A. Synthesis of poly(thiophene-alt-pyrrole) from a difunctionalized thienylpyrrole by Kumada polycondensation. Tetrahedron. 2015;71:5399–5406. doi: 10.1016/j.tet.2015.05.091. DOI

Page Z.A., Duzhko V.V., Emrick T. Conjugated thiophene-containing polymer zwitterions: Direct synthesis and thin film electronic properties. Macromolecules. 2013;46:344–351. doi: 10.1021/ma302232q. DOI

Makarov I.S., Brocklehurst C.E., Karaghiosoff K., Koch G., Knochel P. Synthesis of bicyclo[1.1.1]pentane bioisosteres of internal alkynes and para-disubstituted benzenes from [1.1.1]propellane. Angew. Chem. Int. Ed. 2017;56:12774–12777. doi: 10.1002/anie.201706799. PubMed DOI

Moffatt J.G. Ph.D. Thesis. University of British Columbia; Vancouver, BC, Canada: 1956. A New Method of Phosphorylation and the Synthesis of Some Phosphate Esters of Biological Interest.

Wieghardt K., Chaudhuri P., Nuber B., Weiss J. New triply hydroxo-bridged complexes of chromium(III), cobalt(III), and rhodium(III): Crystal structure of tris(μ-hydroxo)-bis[(l,4,7-trimethyl-l,4,7-triazacyclononane)chromium(III)] triiodide trihydrate. Inorg. Chem. 1982;21:3086–3090. doi: 10.1021/ic00138a032. DOI

Catalytic Hydrolysis of Paraoxon by Immobilized Copper(II) Complexes of 1,4,7-Triazacyclononane Derivatives