Chemistry Commons^™

Solid State And Solution Dynamics Of Pyridine Based Tetraaza- Macrocyclic Lanthanide Chelates Possessing Phosphonate Ligating Functionality (Ln-Pctmb): Effect On Relaxometry And Optical Properties, Garry Kiefer, Mark Woods

Chemistry Faculty Publications and Presentations

The macrocyclic ligand 3,6,9-tris(methylenebutyl phosphonic acid)-3,6,9−15-tetraazabicyclo [9.3.1]pentadeca-1(15),11,13-triene (PCTMB) was synthesized and complexes of Eu³⁺, Tb³⁺, and Gd³⁺ studied by X-ray crystallography, luminescence, and relaxometry. In the crystal these complexes are dimeric and possess 8-coordinate Ln³⁺ centers that are linked by bridging phosphonates. The rigidity introduced by the pyridyl nucleus forces the EuPCTMB and TbPCTMB to adopt a twisted snub disphenoid (TSD) coordination geometry. Examination of the ⁵D₀ → ⁷F₀ luminescent transition of EuPCTMB in the solid state confirmed the existence of a single distinct Eu³⁺ coordination environment, whereas two …

Synthesis And Evaluation Of Lanthanide Ion Dota-Tetraamide Complexes Bearing Peripheral Hydroxyl Groups, Azhar Pasha, Mai Lin, Gyula Tircso, Cynthia L. Rostollan, Mark Woods, Garry Kiefer, A. Dean Sherry, Xiankai Sun

Chemistry Faculty Publications and Presentations

The use of lanthanide-based contrast agents for magnetic resonance imaging has become an integral component of this important diagnostic modality. These inert chelates typically possess high thermodynamic stability constants that serve as a predictor for in vivo stability and low toxicity. Recently, a new class of contrast agents was reported having a significantly lower degree of thermodynamic stability while exhibiting biodistribution profiles indicative of high stability under biological conditions. These observations are suggestive that the nature of contrast agent stability is also dependent upon the kinetics of complex dissociation, a feature of potential importance when contemplating the design of new …

The Effect Of The Amide Substituent On The Biodistribution And Tolerance Of Lanthanide(Iii) Dota-Tetraamide Derivatives, Mark Woods, Peter Caravan, Carlos F.G.C. Geraldes, Matthew T. Greenfield, Garry Kiefer, Mai Lin, Kenneth Mcmillan, M. Isabel M. Prata, Ana C. Santos, Xiankai Sun, Jufeng Wang, Shanrong Zhang, Piyu Zhao, A. Dean Sherry

Chemistry Faculty Publications and Presentations

Objectives—Recent advances in the design of MRI contrast agents have rendered the lanthanide complexes of DOTA-tetraamide ligands of considerable interest, both as responsive MR agents and paramagnetic chemical exchange saturation transfer agents. The potential utility of these complexes for in vivo applications is contingent upon them being well tolerated by the body. The purpose of this study was to examine how the nature of the amide substituent, and in particular its charge, affected the fate of these chelates postinjection.

Materials and Methods—Complexes of 6 DOTA-tetraamide ligands were prepared in which the nature of the amide substituent was systematically …

Synthesis And Relaxometric Studies Of A Dendrimer‐Based Ph‐Responsive Mri Contrast Agent, M. Meser Ali, Mark Woods, Peter Caravan, Ana C.L. Opina, Marga Spiller, James C. Fettinger, A. Dean Sherry

Chemistry Faculty Publications and Presentations

The design of effective pH responsive MRI contrast agents is a key goal in the development of new diagnostic methods for conditions such as kidney disease and cancer. A key factor determining the effectiveness of an agent is the difference between the relaxivity of the “on” state compared to that of the “off” state. In this paper, we demonstrate that it is possible to improve the pH-responsive action of a low molecular weight agent by conjugating it to a macromolecular construct. The synthesis of a bifunctional pH responsive agent is reported. As part of that synthetic pathway we examine the …

Potentiometric And Relaxometric Properties Of A Gadolinium-Based Mri Contrast Agent For Sensing Tissue Ph, Ferenc K. Kálmán, Mark Woods, Peter Caravan, Paul Jurek, Marga Spiller, Gyula Tircso, Róbert Király, Ernő Brücher, A. Dean Sherry

Chemistry Faculty Publications and Presentations

The pH-sensitive contrast agent, GdDOTA-4AmP (Gd1) has been successfully used to map tissue pH by MRI. Further studies now demonstrate that two distinct chemical forms of the complex can be prepared depending upon the pH at which Gd³⁺ is mixed with ligand 1. The desired pH-sensitive form of this complex, referred to here as a Type II complex, is obtained as the exclusive product only when the complexation reaction is performed above pH 8. At lower pH values, a second complex is formed that, by analogy with an intermediate formed during the preparation of GdDOTA, we tentatively assign …

A Bridge To Coordination Isomer Selection In Lanthanide(Iii) Dota-Tetraamide Complexes, Jeff Vipond, Mark Woods, Piyu Zhao, Gyula Tircsó, Jimin Ren, Simon G. Bott, Doug Ogrin, Garry Kiefer, Zoltan Kovacs, A. Dean Sherry

Chemistry Faculty Publications and Presentations

Interest in macrocyclic lanthanide complexes such as DOTA is driven largely through interest in their use as contrast agents for MRI. The lanthanide tetraamide derivatives of DOTA have shown considerable promise as PARACEST agents, taking advantage of the slow water exchange kinetics of this class of complex. We postulated that water exchange in these tetraamide complexes could be slowed even further by introducing a group to sterically encumber the space above the water coordination site, thereby hindering the departure and approach of water molecules to the complex. The ligand 8O₂-bridged-DOTAM was synthesized in a 34% yield from cyclen. …