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This work is licensed under a Creative Commons Attribution 4.0 International License.
Development of Optimized MRI Contrast Agents for Copper(I) Click Reactions
Corresponding Author(s) : Mustafa M. Al-Yassiry
Asian Journal of Chemistry,
Vol. 30 No. 10 (2018): Vol 30 Issue 10, 2018
Abstract
This work has been focused on synthesizing gadolinium(III) 1,4,7-triacetic acid-1,4,7,10- tetraazacyclododecane (DO3A) macrocyclic complexes (GdAa1) as potential T1 MRI contrast agents. Alkyne derivatives chelators were synthesized with three different alkyne pendent arms (butyne) are suitable for Cu(I) catalyzed cycloaddition 'click' chemistry with azide derivatives to form 1,2,3-triazole rings. Triazole formation with benzyl azide was used as "proof of concept" to form chelators and gadolinium complexes (GdAa1) that could be assessed for their properties as MRI contrast agents. One of the complexes was then selected for conjugation with azide derivative of a thymidine DNA base (AZT, a clinically approved drug molecule) to link via triazole group and demonstrate the widespread utility of this approach. Relaxivity measurements were carried out on the synthesized gadolinium(III) complexes to evaluate their potential as MRI contrast agents with GdAa1 showing the highest T1 relaxivity result. Therefore, GdA2a (relaxivity, 5.74 m M-1 s-1) was conjugated with DNA base derivatives (3¢-Azido-3¢-deoxythymidine, AZT) to give the desired product in an 89 % yield with a relaxivity of 4.33 m M-1 s-1 indicating the potential of these compounds for future in vivo applications in MRI studies.
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References
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D.W. Park, S.-H. Ye, H.B. Jiang, D. Dutta, K. Nonaka, W.R. Wagner and K. Kim, Biomaterials, 35, 7851 (2014); https://doi.org/10.1016/j.biomaterials.2014.05.088.
V.P. Mocharla, B. Colasson, L.V. Lee, S. Roper, K.B. Sharpless, C.H. Wong and C. Kolb, Angew. Chem., 44, 116 (2005); https://doi.org/10.1002/anie.200461580.
V.V. Rostovtsev, L.G. Green, V.V. Fokin and K.B. Sharpless, Angew. Chem., 41, 2596 (2002); https://doi.org/10.1002/1521-3773(20020715)41:14<2596::AID-ANIE 2596>3.0.CO;2-4.
S.W. Millward, H.D. Agnew, B. Lai, S.S. Lee, J. Lim, A. Nag, S. Pitram, R. Rohde and J.R. Heath, Integr. Biol., 5, 87 (2013); https://doi.org/10.1039/C2IB20110K.
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R.F.H. Viguier and A.N.J. Hulme, Am. Chem. Soc., 128, 11370 (2006); https://doi.org/10.1021/ja064232v.
P.A. Sukerkar, K.W. MacRenaris, T.R. Townsend, R.A. Ahmed, J.E. Burdette and T.J. Meade, Bioconjug. Chem., 22, 2304 (2011); https://doi.org/10.1021/bc2003555.
P. Wu, A.K. Feldman, A.K. Nugent, C.J. Hawker, A. Scheel, B. Voit, J. Pyun, J.M.J. Frechet, K.B. Sharpless and V.V. Fokin, Angew. Chem. Int. Ed., 43, 3928 (2004); https://doi.org/10.1002/anie.200454078.
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P.A. Furman, J.A. Fyfe, M.H. Stclair, K. Weinhold, J.L. Rideout, G.A. Freeman, S.N. Lehrman, D.P. Bolognesi, S. Broder, H. Mitsuya and D.W. Barry, Acad. Sci. U.S.A., 83, 8333 (1986); https://doi.org/10.1073/pnas.83.21.8333.