Session IV

Tuesday, May 23rd

Session IV



Development of Iron(III) Macrocyclic Complexes as T1 MRI agents

Didar Asik, Eric M. Snyder and Janet R. Morrow

University at Buffalo, Department of Chemistry

Magnetic resonance imaging (MRI) is a non-invasive and high resolution imaging technique that has been primarily used to image tumors, diseases of the liver or heart, abnormalities in pancreas and physiological processes of the body over the last three decades. The MRI signal is modulated by the longitudinal and transverse relaxation processes (r1 and r2) of water protons. To improve contrast between tissues and increase signal intensity in MR images, MRI contrast agents (CAs) that change the longitudinal and transverse relaxation times (T1 and T2) are used. Gd(III) based contrast agents have been notably successful as clinically-approved contrast agents due to their inherent magnetic properties. However, Gd(III) ion is not naturally found in the human body and there are concerns about the risk of its toxicity, particularly in long-term exposure. Patients with Nephrogenic Systemic Fibrosis (NSF) are at greater risk due to compromised kidney function. Due to these potential risks, researchers have been motivated to discover alternative Gd(III)-free T1 contrast agents. High spin Mn(II) and Fe(III) transition metals are considered as potential alternatives because their relatively long electronic relaxation times lead to enhanced T1 relaxation enhancement. Our goal is to develop new Fe(III)-based T1 MRI contrast agents. Key parameters towards the design of our Fe(III) T1 contrast agents include; interaction with surrounding water molecules, rotational correlation time, magnetic susceptibility and stability of the complexes in biological medium. Furthermore, our results show that our Fe(III) MRI agents minimized Fenton processes from occurring, greatly reducing the production of reactive oxygen species (ROS). Imaging studies were performed on a 4.7T MRI scanner at Roswell Park Cancer Institute. Preliminary results are promising and encouraging in the development of safer, cost effective alternatives to clinically used  Gd(III) T1 contrast agents.


Cobalt (II) coordination polymer recovery of crystallinity upon guest absorption in water

Cressa Ria Fulong and Timothy R. Cook

University at Buffalo, Department of Chemistry

A self-assembled Co (II) coordination polymer known as a “crystalline sponge” (CoSP) for its host/guest chemistry was investigated for its ability to encapsulate Orange G (OG) and Methylene blue (MB) in water. Powder X-ray diffraction (PXRD) showed a loss of crystallinity upon solvent removal to furnish a semi-amorphous material (a-CoSP, activated). This semi-amorphous material encapsulated OG and MB, removing the dyes from aqueous solution as evidenced by UV-Vis. PXRD of a-CoSP + H2O (or OG) revealed an increased crystallinity upon guest uptake. Reactivation releases some guest due to deconstruction of the coordination framework; however, the soluble building blocks may regenerate the CoSP under ambient conditions.


Solution studies of macrocyclic transition metal complexes with potential MRI contrast applications

Christopher Bond and Janet Morrow

University at Buffalo, Department of Chemistry

First row transition metal complexes show great potential for use as T1 and chemical exchange saturation transfer(CEST) magnetic resonance imaging (MRI) contrast agents.  These agents incorporate paramagnetic metals to change the magnetic properties of the surrounding water molecules.  However, optimizing these agents for contrast purposes has proven to be challenging, as small alterations to an agent can have a large impact on how the agents interact with surrounding water molecules, and thus change their potential contrast properties.  Currently, we are using various 1H-NMR and 17O-NMR techniques to analyze various paramagnetic Fe(II), Fe(III), and Co(II) complexes in order to gain a greater understanding of inner sphere and second sphere water interactions.  Our results suggest that contrast properties of agents are significantly impacted by second sphere water interaction (such as water hydrogen bonding to the paramagnetic agents), and challenges the current dogma in chemical literature, that often focuses solely on water bound directly to paramagnetic metal center of the agents.


Coordination Driven Self-Assembled Cofacial Catalyst for Oxygen Reduction

Amanda Oldacre, Alan E. Friedman, Timothy R. Cook

University at Buffalo, Department of Chemistry

The large kinetic barriers associated with redox chemistry of relevance to energy storage can be circumvented by catalytic pathways. Cofacial catalysts that are capable of small molecule activation allow for preorganization of transition states and enable two or more metals to participate, which decreases the demand on a single metal center.  Metalloporphyrins can be assembled into a cofacial conformations using molecular clips that enforce an offset between the two macrocycles. Herein, we describe a system that assembles cobalt 5,10,15,20–tetra(4–pyridyl) porphyrins (Co–TPyP) with diruthenium clips to furnish [Ru8(η6–p–PriC6H4Me)8(Co–TPyP)2(C6H2O4)4](O3SCF3)8 (Co prism). Catalytic activity towards the reduction of oxygen is shown in both Co–TPyP and the Co prism. This work encompasses the electrochemical oxygen reduction by homogeneous solutions of Co–TPyP and Co Prism.


Co(II) complexes with innersphere and outersphere water interactions for CEST MRI applications

Samira Abo-Zeid1, Eric M. Snyder1, Alexander Nazarenko2 and Janet R. Morrow1

1University at Buffalo, Department of Chemistry

2Buffalo State College, Department of Chemistry

High spin Co(II) complexes are excellent paramagnetic shift agents for MRI applications.  Macrocyclic ligands with pendent alcohol or amide groups stabilize the divalent oxidation state and either encapsulate the Co(II) or leave an open coordination site for bound water. These complexes are paraCEST agents, but also produce highly paramagnetically shifted water protons due to both outersphere and innersphere interactions. Two sets of Co(II) complexes including one that contains an open coordination site and one that lacks an open coordination site for binding water were compared. The water exchange rate constants are consistent with a rapidly exchanging innersphere water that cannot give rise to a CEST effect. Remarkably, both the saturated and unsaturated Co(II) complexes substantially shift the 1H and 17O NMR resonances of bulk water.  Co(II) induced proton water Shifts approach that of one of the best lanthanide agents, Tm(DOTA).


Improving Quantum Yields of Platinum Alkynyl Complexes:  Two Strategies Towards the Same Goal

Cory Hauke, Yuzhen Zhang, Timothy R. Cook

University at Buffalo, Department of Chemistry

Understanding how to maximize the quantum yield of phosphorescent molecules is an important tool in aiding the rational design of photophysically active molecules for applications such as light emitting devices.  Herein, we demonstrate two strategies to increase the quantum of an alkynyl platinum complex, (4-ethynylpyridyl)2(N-heterocyclic carbene)2Pt, with a quantum yield of 1.2% in DCM solution.  The first uses coordination-driven self-assembly to increase the radiative rate of emission, thereby increasing the quantum yield to 14%.  The second uses methylation of the pyridyl nitrogen to create a more rigid structure via extending the pi system of the molecule to lower the non-radiative rate constant, thereby increasing the quantum yield to 39%.