Journal of Organic and Biomolecular Simulations

A Quantum Mechanical Study of Structural and Electronic Dilution Effects in Paramagnetic Chemical Exchange Saturation Transfer Agents

Whelton A. Miller III and Preston B. Moore

DOI : 10.3844/jobsp.2014.1.13

Journal of Organic and Biomolecular Simulations

Volume 1, Issue 1

Pages 1-13


We present a computational study of the effect of chemical modifications of the meta and para substituents in the coordinating pendant arm of a modified 1,4,7,10-tetraazacyclododecane-N, N’, N’’, N’’’-tetraamide (DOTAM) ligand on the Chemical Exchange Saturation Transfer (CEST) signal. Magnetic Resonance Imaging (MRI) is currently one of the most widely used techniques available. MRI has led to a new class of pharmaceuticals termed “imagining” or “contrast” agents. These agents usually work by incorporating lanthanide metals such as Gadolinium (Gd) and Europium (Eu). This allows the contrast agents to take advantage of the paramagnetic properties of the metals, which in turn enhances the signal detectable by MRI. The effect of simple electron-withdrawing (e.g., nitro) and electron-donating (e.g., methyl) substituents chemically attached to a modified chelate arm (pendant arm) is quantified by charge transfer interactions in the coordinated water-chelate system computed from quantum mechanics. This study attempts to reveal the origin of the substituent effect on the CEST signal and the electronic structure of the complex. We find that the extent of Charge Transfer (CT) depends on orbital orientations and overlaps. However, CT interactions occur simultaneously from all arms, which causes a dilution effect with respect to the pendant arm.


© 2014 Whelton A. Miller III and Preston B. Moore. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.