Title of Research Project
Major
MS Chemistry
Research Abstract
Paramagnetic Chemical Exchange Saturation Transfer (PARACEST) agents are lanthanide complexes that generate contrast through the slow-to-intermediate exchange of paramagnetically-shifted protons or water molecules. Although PARACEST agents have shown promise as molecular imaging agents, in-vivostudies have been limited due to the masking of the CEST signal by spin-relaxation exchange (T2ex) and Magnetization Transfer (MT) effects. The majority of PARACEST agents studied to date have been Ln(III)DOTA-tetraamides which can either adopt the square antiprismatic (SAP) or twisted square antiprismatic (TSAP) geometries in solution. The more compact nature of the SAP isomer, combined with its slower bound-water exchange kinetics, makes it the preferred isomer for PARACEST applications that rely on water exchange as the primary contrast mechanism. We hypothesize that both the T2ex and the MT effect could simultaneously be overcome by developing complexes that preferentially adopt the TSAP geometry and induce contrast through amide proton exchange. Our current goal is to determine if a preference for TSAP geometry is consistent with ligands containing a pyridine moiety regardless of the identity of the other amide side-chains. To this end, three pyridine-containing complexes have been synthesized and characterized. The luminescent and PARACEST properties will be studied.
Faculty Mentor/Advisor
Dr. Evbuomwan
Included in
Effect of a coordinating pyridine moiety on the SAP and TSAP isomer populations of bimodal Lanthanide (III) complexes
Paramagnetic Chemical Exchange Saturation Transfer (PARACEST) agents are lanthanide complexes that generate contrast through the slow-to-intermediate exchange of paramagnetically-shifted protons or water molecules. Although PARACEST agents have shown promise as molecular imaging agents, in-vivostudies have been limited due to the masking of the CEST signal by spin-relaxation exchange (T2ex) and Magnetization Transfer (MT) effects. The majority of PARACEST agents studied to date have been Ln(III)DOTA-tetraamides which can either adopt the square antiprismatic (SAP) or twisted square antiprismatic (TSAP) geometries in solution. The more compact nature of the SAP isomer, combined with its slower bound-water exchange kinetics, makes it the preferred isomer for PARACEST applications that rely on water exchange as the primary contrast mechanism. We hypothesize that both the T2ex and the MT effect could simultaneously be overcome by developing complexes that preferentially adopt the TSAP geometry and induce contrast through amide proton exchange. Our current goal is to determine if a preference for TSAP geometry is consistent with ligands containing a pyridine moiety regardless of the identity of the other amide side-chains. To this end, three pyridine-containing complexes have been synthesized and characterized. The luminescent and PARACEST properties will be studied.
