Brightly Luminescent and Kinetically Inert Lanthanide Bioprobes Based on Linear and Preorganized Chelators.
The synthesis, photophysical properties, and kinetic stability of a series of water-soluble, highly emissive Tb(III) and Eu(III) complexes featuring triethylenetetraamine hexaacetic acid (TTHA) and cyclohexyl triethylenetetraamine hexaacetic acid (cyTTHA) chelator scaffolds and carbostyril sensitizers are reported. The unique and modular design of the chelators gives rise to striking quantum yields of emission in aqueous solutions (up to 54%) as well as the characteristic lanthanides' photophysical properties (long excited-state lifetimes, large effective Stokes shifts, and narrow emission peaks). Furthermore, the preorganized chelators (L3, L4, and L6) bind metal within minutes at ambient temperature yet exhibit substantial resistance to transchelation in the presence of a challenge solution (EDTA, 1 mM). Moreover, the Eu(III) complex of L4 remains stably luminescent in HeLa cells over hours, demonstrating the suitability of these compounds for live-cell imaging applications. Representative chelators suitable for derivatization and protein bioconjugation were also prepared that were functionalized with clickable azide and alkyne moieties, biotin, and trimethoprim (TMP). With exceptional long-wavelength brightness, enhanced kinetic inertness, and an adaptable synthetic route, the reported lanthanide complexes are promising probes and labels for time-gated bioanalysis, biosensing, and optical microscopy.
Department of Chemistry, University of Illinois at Chicago , 845 West Taylor Street, MC 111, Chicago, Illinois 60607, United States.
Ali
A
Mohamadi
Department of Chemistry, University of Illinois at Chicago , 845 West Taylor Street, MC 111, Chicago, Illinois 60607, United States.
Lawrence W
LW
Miller
J Am Chem Soc. 2001 Jul 25;123(29):7067-73
11459485
Chem Rev. 2002 Jun;102(6):1977-2010
12059260
Eur J Med Chem. 2004 May;39(5):467-72
15110973
Cytometry A. 2006 Sep 1;69(9):1020-7
16888769
Chem Commun (Camb). 2007 May 7;(17):1716-8
17457418
J Microsc. 2007 Dec;228(Pt 3):390-405
18045334
Chemistry. 2008;14(6):1726-39
18098236
Bioconjug Chem. 2008 May;19(5):1105-11
18442281
Dalton Trans. 2008 Aug 21;(31):4138-51
18688432
Chemistry. 2009;15(4):885-900
19065695
Angew Chem Int Ed Engl. 2009;48(27):4990-2
19492378
Inorg Chem. 2009 Jul 20;48(14):6692-712
19507818
Analyst. 2010 Jan;135(1):42-52
20024180
Bioconjug Chem. 2010 Feb 17;21(2):319-27
20085336
Cytometry A. 2010 Dec;77(12):1113-25
20824630
Bioconjug Chem. 2011 Jul 20;22(7):1402-9
21619068
J Am Chem Soc. 2011 Dec 14;133(49):19900-10
22010878
Chemistry. 2012 Aug 27;18(35):10825-9
22807190
Inorg Chem. 2012 Nov 19;51(22):12575-89
23106422
Inorg Chem. 2013 Feb 18;52(4):1694-700
23126285
J Am Chem Soc. 2013 Jan 23;135(3):1102-9
23231786
Chem Commun (Camb). 2013 Feb 25;49(16):1600-2
23336102
Inorg Chem. 2014 Feb 17;53(4):1839-53
24144069
Chem Rev. 2014 Apr 23;114(8):4496-539
24328202
Angew Chem Int Ed Engl. 2014 Sep 26;53(40):10718-22
25115848
Dalton Trans. 2015 Mar 21;44(11):4994-5003
25612290
Bioconjug Chem. 2015 Mar 18;26(3):460-5
25675354
FASEB J. 2015 Jun;29(6):2235-46
25690655
Biophys J. 2015 Jul 21;109(2):240-8
26200860
Chemistry. 2016 Jan 11;22(2):570-80
26671263
Methods Appl Fluoresc. 2014 Aug 22;2(3):037001
29148472
Anal Biochem. 1997 Jun 1;248(2):216-27
9177747