Is Macrocycle a Synonym for Kinetic Inertness in Gd(III) Complexes? Effect of Coordinating and Noncoordinating Substituents on Inertness and Relaxivity of Gd(III) Chelates with DO3A-like Ligands
ABSTRACT Gadolinium chelates with octadentate ligands are widely used as contrast agents for magnetic resonance imaging (MRI), with macrocyclic ligands based on DO3A being preferred for the high kinetic inertness of their Gd chelates. A major challenge in the design of new bifunctional MRI probes is the need to control the rotational motion of the chelate, which greatly affects its relaxivity. In this work we explored facile alkylation of a secondary amine in macrocyclic DO3A-like ligands to create a short, achiral linkage to limit the undesired internal motion of chelates within larger molecular constructs. The acetate moiety on the trans nitrogen was also replaced with either a bidentate (ethoxyacetate, L1 or methyl picolinate, L2) or bulky monodentate (methyl phosphonate, L3) donor arm to give octa- or heptadentate ligands, respectively. The resultant Gd(III) complexes were all monohydrated (q = 1) and exhibited water residency times that spanned 2 orders of magnitude (τM = 2190 ± 170, 3500 ± 90, and 12.7 ± 3.8 ns at 37 °C for GdL1, GdL2, and GdL3, respectively). Alkylation of the secondary amine with a noncoordinating biphenyl moiety resulted in coordinatively saturated q = 0 complexes of octadentate ligands L1 and L2. Relaxivities were limited by slow water exchange and/or lack of water coligand. All complexes showed decreased inertness compared to [Gd(DO3A)] despite higher ligand denticity, and inertness was further decreased upon N-alkylation. These results demonstrate that high kinetic inertness and in vivo safety of Gd chelates with macrocyclic ligands should not be generalized.
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ABSTRACT: 2, 6-bis (5,6-dipropyl-1,2,4-triazine-3-yl) pyridine (BDPTP) was synthesized with 2, 6 - dimethyl pyridine and ethyl butyrate as raw materials. And characterized by IR, 1HNMR and element analysis etc. The extraction performance of this kind of complexes for four kinds of cations, Cu II ,Cd II ,Pb II ,Ni II is studied in hydrochloric acid system. The results show that the extraction rate of cadmium chloride with BDPTP in dichloromethane can reach to 97.25%. It is meaningful to cadmium chloride wastewater treatment.03/2014; DOI:10.2991/icmaee-14.2014.21
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ABSTRACT: Contrast agents are diagnostic tools that often complement magnetic resonance imaging. At ultra-high field strengths (≥7 T), magnetic resonance imaging is capable of generating desirable high signal-to-noise ratios, but clinically available contrast agents are less effective at ultra-high field strengths relative to lower fields. This gap in effectiveness demands the development of contrast agents for ultra-high field strengths. In this minireview, we summarize contrast agents reported during the last three years that focused on ultra-high field strengths.The Analyst 07/2014; 139(18). DOI:10.1039/c4an00990h · 3.91 Impact Factor
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ABSTRACT: A three-step route was used to synthesize 1,7-bis(t-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane (DO2A-t-Bu ester) from 1,4,7,10-tetraazacyclododecane (cyclen). The overall time of reaction was reduced from a combined ~56 h to 2.3 h with an overall yield comparable to previously reported methods.Tetrahedron Letters 10/2014; 55(40):5560–5561. DOI:10.1016/j.tetlet.2014.08.026 · 2.39 Impact Factor