Metallostar Assemblies Based on Dithiocarbamates for Use as MRI Contrast Agents

Abstract

Two different octadentate gadolinium chelates based on DO3A and DOTAGA chelates (hydration number q = 1) have been used to prepare a series of bi-, tri-and tetrametallic d-f mixed-metal complexes. The piperazine-based dithiocarbamate linker ensures that rotation of the gadolinium chelates is restricted, leading to enhanced relaxivity (r1) values, which increase with overall mass and the number of gadolinium units. The r1 value (at 10 MHz, 25 °C) per Gd unit rises from 5.0 mM −1 s −1 for the Gd-DO3A-NH2 monogadolinium chelate to 9.2 mM −1 s −1 in a trigadolinium complex with a ruthenium(III) core. Using a 1.5 T clinical scanner operating at 63.87 MHz (25 °C), an 86% increase in relaxivity per gadolinium unit is observed for this multimetallic compound compared to clinically-approved Dotarem. The gadolinium complexes based on the DOTAGA chelate also performed well at 63.87 MHz, with a relaxivity value of 9.5 mM −1 s −1 per gadolinium unit being observed for the trigadolinium d-f mixed-metal complex with a ruthenium(III) core. The versatility of dithiocarbamate coordination chemistry thus provides access to a wide range of d-f hybrids with potential for use as high-performance MRI contrast agents.

Metal−Organic Polyhedron with Four Fe(III) Centers Producing Enhanced T1 Magnetic Resonance Imaging Contrast in Tumors

“…Additionally, the increased rigidity helps minimize localized molecular motions which may reduce relaxation enhancement as observed in polymer and metallostar-based contrast agents. 46,47 The MOPs were synthesized with careful stochiometric control in methanol using six equivalents of ligand to four equivalents of trivalent metal salts. The Fe(III) reaction mixtures changed from a green to blue to deep red with increasing additions of KOH indicative of the formation of triscatecholate Fe(III) centers.…”

“…Rigidity in the catecholamide ligand is important to form discrete MOPs, as it prevents the ligand from chelating the same metal center with both catecholate donors. Additionally, the increased rigidity helps minimize localized molecular motions which may reduce relaxation enhancement as observed in polymer and metallo-star-based contrast agents. , …”

Gadolinium Complexes Attached to Poly Ethoxy Ethyl Glycinamide (PEE‐G) Dendrons: Magnetic Resonance Imaging Contrast Agents with Increased Relaxivity

“…A ligand matching both criteria was a DOTA derivative, DOTAGA (GA for glutamic acid) . Reassuringly, studies have demonstrated the robust nature of Gd(III) complexes formed with this ligand, and no significant toxicity has been observed, even with compounds presenting multiple metal complexes …”

Consolidation of Gold and Gadolinium Nanoparticles: An Extra Step towards Improving Cancer Imaging and Therapy

“…Cyclic disulfides, which form dithiolates on attachment to the surface [88], have also been applied as dithiocarbamates [89]. Dithiocarbamates have been shown to displace thiols on gold nanoparticle surfaces in a vigorous manner [90]. There are many chelators developed connecting Gd to AuNPs, but the cyclic 10-tetraacetic acid (DOTA) is preferred due to its kinetic inertness [91].…”