title: Synthesis and relaxivity studies of a DOTA-based nanomolecular chelator assembly supported by an icosahedral closo-B₁₂²⁻ core for MRI: a click chemistry approach.
abstract: An icosahedral closo-B₁₂²⁻ scaffold based nano-sized assembly capable of carrying a high payload of Gd³⁺-chelates in a sterically crowded configuration is developed by employing the azide-alkyne click reaction. The twelve copies of DO3A-t-Bu-ester ligands were covalently attached to an icosahedral closo-B₁₂²⁻ core via suitable linkers through click reaction. This nanomolecular structure supporting a high payload of Gd³⁺-chelate is a new member of the closomer MRI contrast agents that we are currently developing in our laboratory. The per Gd ion relaxivity (r₁) of the newly synthesized MRI contrast agent was obtained in PBS, 2% tween/PBS and bovine calf serum using a 7 Tesla micro MRI instrument and was found to be slightly higher (r₁ = 4.7 in PBS at 25 °C) compared to the clinically used MRI contrast agents Omniscan (r₁ = 4.2 in PBS at 25 °C) and ProHance (r₁ = 3.1 in PBS at 25 °C).
authors.affiliation: International Institute of Nano and Molecular Medicine, School of Medicine, University of Missouri, Columbia, MO 65211-3450, USA.
authors.forename: Lalit N
authors.initials: LN
authors.lastname: Goswami
authors.forename: Lixin
authors.initials: L
authors.lastname: Ma
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kueffer
authors.forename: Satish S
authors.initials: SS
authors.lastname: Jalisatgi
authors.forename: M Frederick
authors.initials: MF
authors.lastname: Hawthorne
mesh_terms: D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D057930:Click Chemistry; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D008024:Ligands; D008279:Magnetic Resonance Imaging; D009942:Organometallic Compounds / Q000737:chemistry
chemical_list: C493794:1,4,7-tris(tert-butylacetate)-1,4,7,10-tetraazacyclododecane ester; D000480:Alkynes; D001386:Azides; D002614:Chelating Agents; D003287:Contrast Media; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D008024:Ligands; D009942:Organometallic Compounds; C062402:gadoteridol; D005682:Gadolinium
references.citation: Inorg Chem. 2013 Feb 18;52(4):1694-700
references.pmid: 23126285
references.citation: J Am Chem Soc. 2010 Sep 22;132(37):12829-31
references.pmid: 20795620
references.citation: Contrast Media Mol Imaging. 2006 Sep-Oct;1(5):184-8
references.pmid: 17193695
references.citation: Chem Commun (Camb). 2013 May 4;49(34):3579-81
references.pmid: 23525129
references.citation: J Am Chem Soc. 2011 Mar 2;133(8):2390-3
references.pmid: 21294571
references.citation: Contrast Media Mol Imaging. 2007 Mar-Apr;2(2):67-71
references.pmid: 17451189
references.citation: Bioconjug Chem. 2008 Aug;19(8):1505-9
references.pmid: 18620446
references.citation: Angew Chem Int Ed Engl. 2002 Jul 15;41(14):2596-9
references.pmid: 12203546
references.citation: Dalton Trans. 2008 Jun 21;(23):3027-47
references.pmid: 18521444
references.citation: J Am Chem Soc. 2008 May 28;130(21):6662-3
references.pmid: 18452288
references.citation: J Am Chem Soc. 2011 Aug 17;133(32):12382-5
references.pmid: 21766843
references.citation: J Am Chem Soc. 2001 Oct 31;123(43):10758-9
references.pmid: 11674017
references.citation: Angew Chem Int Ed Engl. 2007;46(7):1018-25
references.pmid: 17211903
references.citation: Inorg Chem. 2004 Mar 22;43(6):2018-20
references.pmid: 15018524
references.citation: J Am Chem Soc. 2005 Dec 28;127(51):18243-51
references.pmid: 16366578
references.citation: Inorg Chem. 2013 Feb 18;52(4):1701-9
references.pmid: 23391150
references.citation: Chem Rev. 1999 Sep 8;99(9):2293-352
references.pmid: 11749483
references.citation: Angew Chem Int Ed Engl. 2005 Feb 25;44(10):1480-4
references.pmid: 15580594
references.citation: Acc Chem Res. 2009 Jul 21;42(7):851-62
references.pmid: 19222207
references.citation: Toxicology. 2008 Jun 27;248(2-3):77-88
references.pmid: 18440117
references.citation: Contrast Media Mol Imaging. 2009 Mar-Apr;4(2):89-100
references.pmid: 19177472
references.citation: Angew Chem Int Ed Engl. 2011 May 9;50(20):4689-91
references.pmid: 21480453