Skip to main content
SpringerLink
Log in

Copper complexes as a source of redox active MRI contrast agents

  • Published:
BioMetals Aims and scope Submit manuscript

Abstract

The study reports an advance in designing copper-based redox sensing MRI contrast agents. Although the data demonstrate that copper(II) complexes are not able to compete with lanthanoids species in terms of contrast, the redox-dependent switch between diamagnetic copper(I) and paramagnetic copper(II) yields a novel redox-sensitive contrast moiety with potential for reversibility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Aime S, Castelli DD, Crich SG, Gianolio E, Terreno E (2009) Pushing the sensitivity envelope of lanthanide-based magnetic resonance imaging (MRI) contrast agents for molecular imaging applications. Acc Chem Res 42:822–831

    Article  CAS  PubMed  Google Scholar 

  • Angelovski G, Fouskova P, Mamedov I, Canals S, Toth E, Logothetis NK (2008) Smart magnetic resonance imaging agents that sense extracellular calcium fluctuations. ChemBioChem 9:1729–1734

    Article  CAS  PubMed  Google Scholar 

  • Badero OJ, Schlanger L, Rizk D (2008) Gadolinium nephrotoxicity: case report of a rare entity and review of the literature. Clin Nephr 70:518–522

    Article  CAS  Google Scholar 

  • Bentfeld R, Ehlers N, Mattes R (1995) Synthesis and characterization of copper(II) complexes of a 14-membered cis-N2S2 dibenzo macrocycle and of its bis-acetato and bis(methylpyridyl) derivatives. Chem Ber 128:1199–1205

    Article  CAS  Google Scholar 

  • De Leon-Rodriguez LM, Lubag AJM, Malloy CR, Martinez GV, Gillies RJ (2009) Sherry AD responsive MRI agents for sensing metabolism in vivo. Acc Chem Res 42:948–957

    Article  PubMed Central  PubMed  Google Scholar 

  • Di Marco M, Sadun C, Port M, Guilbert I, Couvreur P, Dubernet C (2007) Physicochemical characterization of ultrasmall superparamagnetic iron oxide particles (USPIO) for biomedical application as MRI contrast agents. Int J Nanomed 2:609–622

    Google Scholar 

  • Dorazio S, Morrow JR (2012) The Development of Iron(II) Complexes as ParaCEST MRI Contrast Agents. Eur J Inorg Chem 12:2006–2014

    Article  Google Scholar 

  • Drahos B, Lukes I, Toth E (2012) Manganese(II) Complexes as Potential Contrast Agents for MRI. Eur J Inorg Chem 12:1975–1986

    Article  Google Scholar 

  • Farrugia LJ (1999) WinGX suite for small-molecule single-crystal crystallography. J Appl Crystallogr 32:837–838

    Article  CAS  Google Scholar 

  • Filippin LI, Vercelino V, Marroni NP, Xavier RM (2008) Redox signalling and the inflammatory response in rheumatoid arthritis. Clin Exper Immunol 152:415–422

    Article  CAS  Google Scholar 

  • Funkemeier D, Mattes R (1993) Synthesis and structural studies of copper(II), nickel(II) and cobalt(II) complexes of a 14-membered trans-N2S2 dibenzo macrocycle with 2 pendant pyridylmethyl groups. J Chem Soc Dalton Trans 8:1313–1319

    Article  Google Scholar 

  • Gale EM, Mukherjee S, Liu C, Loving GS, Caravan P (2014) Structure–Redox–Relaxivity relationships for redox responsive manganese-based magnetic resonance imaging probes. Inorg Chem 53:10748–10761

    Article  CAS  PubMed  Google Scholar 

  • Grant D, Refsum H, Rummeny E, Marchal G (1997) Liver imaging: clinical applications and future perspectives. Acta Radiol 38:623–630

    Article  CAS  PubMed  Google Scholar 

  • Hancu I, Dixon WT, Woods M, Vinogradov E, Sherry AD, Lenkinski RE (2010) CEST and PARACEST MR contrast agents. Acta Radiol 51:910–923

    Article  PubMed  Google Scholar 

  • Iwaki S, Hanaoka K, Piao W, Komatsu T, Ueno T, Terai T, Nagano T (2012) Development of hypoxia-sensitive Gd3+ -based MRI contrast agents. Bioorg Med Chem Lett 22:2798–2892

    Article  CAS  PubMed  Google Scholar 

  • Kueny-Stotz M, Garofalo A, Felder-Flesch D (2012) Manganese-Enhanced MRI Contrast Agents: From Small Chelates to Nanosized Hybrids. Eur J Inorg Chem 12:1987–2005

    Article  Google Scholar 

  • Kupka T, Dziegielewski JO, Pasterna G, Malecki JG (1992) Copper-D-penicillamine complex as potential contrast agent for MRI. Mag Reson Imag 10:855–858

    Article  CAS  Google Scholar 

  • Lauffer RB (1987) Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: theory and design. Chem Rev 87:901–927

    Article  CAS  Google Scholar 

  • Ledneva E, Karie S, Launay-Vacher V, Janus N (2009) Deray G renal safety of gadolinium-based contrast media in patients with chronic renal insufficiency. Radiology 250:618–628

    Article  PubMed  Google Scholar 

  • Longmire M, Choyke PL, Kobayashi H (2008) Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. Nanomed 3:703–717

    Article  CAS  Google Scholar 

  • Loving GS, Mukherjee S, Caravan P (2013) Redox-activated manganese-based MR contrast agent. J Amer Chem Soc 135:4620–4623

    Article  CAS  Google Scholar 

  • Mattes R, Muhlenbrock C, Leeners K, Pyttel C (2004) Metal complexes with N2O2S2 donor set. Synthesis and characterization of the cobalt(II), nickel(II), and copper(II) complexes of a 15-and a 16-membered bis(2-hydroxyethyl) pendant macrocyclic ligand. Z Anorg Allg Chem 630:722–729

    Article  CAS  Google Scholar 

  • Min C, Shao H, Liong M, Yoon T-J, Weissleder R, Lee H (2012) Mechanism of magnetic relaxation switching sensing. ACS Nano 6:6821–6828

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Persson I (2010) Hydrated metal ions in aqueous solution: how regular are their structures? Pure Appl Chem 82:1901–1917

    Article  CAS  Google Scholar 

  • Profumo E, Buttari B, Rigano R (2011) Oxidative stress in cardiovascular inflammation: its involvement in autoimmune responses, Int J Inflamm Article ID 295705

  • Sheldrick GM, SHELXL-97 (1998) Programs for crystal structure analysis (release 97-2), Institut für Anorganische Chemie der Universität Göttingen, Tammanstrasse 4, D-3400 Gottingen, Germany

  • Sherry AD, Wu YK (2013) The importance of water exchange rates in the design of responsive agents for MRI. Curr Opin Chem Biol 17:167–174

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sowden RJ, Trotter KD, Dunbar L, Craig G, Erdemli O, Spickett CM, Reglinski J (2013) Reactions of copper macrocycles with antioxidants and HOCl: potential for biological redox sensing. Biometals 26:85–95

    Article  CAS  PubMed  Google Scholar 

  • Taylor MK, Trotter KD, Reglinski J, Berlouis LEA, Kennedy AR, Spickett CM, Sowden RJ (2008) Copper N2S2 Schiff base macrocycles: the effect of structure on redox potential. Inorg Chim Acta 361:2851–2862

    Article  CAS  Google Scholar 

  • Thunus L, Lejeune R (1999) Overview of transition metal and lanthanide complexes as diagnostic tools. Coord Chem Revs 184:125–155

    Article  Google Scholar 

  • Tobe ML (1972) Inorganic reaction mechanisms. Thomas Nelson & Sons Ltd, London

    Google Scholar 

  • Trotter KD, Reglinski J, Robertson K, Forgie JC, Parkinson JA, Kennedy AR, Armstrong DR, Sowden RJ, Spickett CM (2009) Structural studies of trans-N2S2 Copper macrocycles. Inorg Chim Acta 362:4065–4072

    Article  CAS  Google Scholar 

  • Trotter KD, Taylor MK, Forgie JC, Reglinski J, Berlouis LEA, Kennedy AR, Spickett CM, Sowden RJ (2010) The structural and electrochemical consequences of hydrogenating Copper N2S2 Schiff base macrocycles. Inorg Chim Acta 363:1529–1538

    Article  CAS  Google Scholar 

  • Tsitovich PB, Burns PJ, Mckay AM, Morrow JR (2014) Redox-activated MRI contrast agents based on lanthanide and transition metal ions. J Inorg Biochem 133:143–154

    Article  CAS  PubMed  Google Scholar 

  • Viger ML, Sankaranarayanan J, de Gracia Lux C, Chan M, Almutairi A (2013) Collective activation of MRI agents via encapsulation and disease-triggered release. J Am Chem Soc 135:7847–7850

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Vologdin N, Rolla GA, Botta M, Tei L (2013) Orthogonal synthesis of a heterodimeric ligand for the development of the Gd-III-Ga-III ditopic complex as a potential pH-sensitive MRI/PET probe. Org Biomol Chem 11:1683–1690

    Article  CAS  PubMed  Google Scholar 

  • Weast RC (1980) Handbook of chemistry and physics, 60th edn. CRC Press, Boca Raton

    Google Scholar 

  • Yam VWW, Lo KKW (1999) Recent advances in utilization of transition metal complexes and lanthanides as diagnostic tools. Coord Chem Rev 184:157–240

    Article  Google Scholar 

  • Yu M, Beyers RJ, Gorden JD, Cross NJ, Goldsmith CR (2012) A magnetic resonance imaging contrast agent capable of detecting hydrogen peroxide. Inorg Chem 51:9153–9155

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

L.D., K.D.T., M.K.T. and D.S. would like to thank Strathclyde University and WestChem for financial assistance. J.R., C.M.S. and R.J.S. gratefully acknowledge the support of the BBSRC (BBS/B/01553).

Author information

Author notes

  1. Corinne M. Spickett

    Present address: School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK

  2. Michelle K. Taylor

    Present address: School of Science and Technology, University of New England, Armidale, NSW 2351, Australia

Authors and Affiliations

  1. Department of Pure & Applied Chemistry, Strathclyde University, 295 Cathedral St., Glasgow, G1 1XL, UK

    Lynsey Dunbar, Katherine D. Trotter, Michelle K. Taylor, David Smith, Alan R. Kennedy & John Reglinski

  2. Strathclyde Institute of Pharmacy and Biomedical Sciences, Strathclyde University, 27 Taylor Street, Glasgow, G4 0NR, UK

    Rebecca J. Sowden & Corinne M. Spickett

Authors
  1. Lynsey Dunbar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rebecca J. Sowden
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katherine D. Trotter
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michelle K. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alan R. Kennedy
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. John Reglinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Corinne M. Spickett
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John Reglinski.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10534_2015_9875_MOESM1_ESM.doc

Details of the X-ray crystal structure determination of [Cu(II)SprNen(-(CH2)3OH)2] 2BF4 may be obtained from the CCDC; e-mail deposit@ccdc.cam.ac.uk or www:http://ccdc. cam.ac.uk) on request quoting the depository numbers ccdc 953160. †The supporting information contains details on the competitive binding studies of the macrocycles with BSA. Supplementary material 1 (DOC 65 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dunbar, L., Sowden, R.J., Trotter, K.D. et al. Copper complexes as a source of redox active MRI contrast agents. Biometals 28, 903–912 (2015). https://doi.org/10.1007/s10534-015-9875-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10534-015-9875-3

Keywords

Search

Navigation