Metal-oxo clusters have been used as building blocks to form hybrid nanomaterials and evaluated as potential MRI contrast agents. We have synthesized a biocompatible copolymer based on a water stable, nontoxic, mixed-metal-oxo cluster, Mn8Fe4O12(L)16(H2O)4, where L is acetate or vinyl benzoic acid, and styrene. The cluster alone was screened by NMR for relaxivity and was found to be a promising T2 contrast agent, with r1 = 2.3 mM(-1) s(-1) and r2 = 29.5 mM(-1) s(-1). Initial cell studies on two human prostate cancer cell lines, DU-145 and LNCap, reveal that the cluster has low cytotoxicity and may be potentially used in vivo. The metal-oxo cluster Mn8Fe4(VBA)16 (VBA = vinyl benzoic acid) can be copolymerized with styrene under miniemulsion conditions. Miniemulsion allows for the formation of nanometer-sized paramagnetic beads (~80 nm diameter), which were also evaluated as a contrast agent for MRI. These highly monodispersed, hybrid nanoparticles have enhanced properties, with the option for surface functionalization, making them a promising tool for biomedicine. Interestingly, both relaxivity measurements and MRI studies show that embedding the Mn8Fe4 core within a polymer matrix decreases r2 effects with little effect on r1, resulting in a positive T1 contrast enhancement.

There is an increasing need for gadolinium-free magnetic resonance imaging (MRI) contrast agents, particularly for patients suffering from chronic kidney disease. Using a cluster−nanocarrier combination, we have identified a novel approach to the design of biomedical nanomaterials and report here the criteria for the cluster and the nanocarrier and the advantages of this combination. We have investigated the relaxivity of the following manganese oxo clusters: the parent cluster Mn 3 (O 2 CCH 3 ) 6 (Bpy) 2 (1) where Bpy = 2,2′-bipyridine and three new analogs, Mn 3 (O 2 CC 6 H 4 CHCH 2 ) 6 (Bpy) 2 (2), Mn 3 (O 2 CC(CH 3 )CH 2 ) 6 (Bpy) 2 (3), and Mn 3 O(O 2 CCH 3 ) 6 (Pyr) 2 (4) where Pyr = pyridine. The parent cluster, Mn 3 (O 2 CCH 3 ) 6 (Bpy) 2 (1), had impressive relaxivity (r 1 = 6.9 mM −1 s −1 , r 2 = 125 mM −1 s −1 ) and was found to be the most amenable for the synthesis of cluster-nanocarrier nanobeads. Using the inverse miniemulsion polymerization technique (1) in combination with the hydrophilic monomer acrylamide, we synthesized nanobeads (∼125 nm diameter) with homogeneously dispersed clusters within the polyacrylamide matrix (termed Mn 3 Bpy-PAm). The nanobeads were surfacemodified by co-polymerization with an amine-functionalized monomer. This enabled various postsynthetic modifications, for example, to attach a near-IR dye, Cyanine7, as well as a targeting agent. When evaluated as a potential multimodal MRI contrast agent, high relaxivity and contrast were observed with r 1 = 54.4 mM −1 s −1 and r 2 = 144 mM −1 s −1 , surpassing T 1 relaxivity of clinically used Gd-DTPA chelates as well as comparable T 2 relaxivity to iron oxide microspheres. Physicochemical properties, cellular uptake, and impacts on cell viability were also investigated.

Addition of amino acids, glycine, alanine, and serine, to poorly soluble copper(II) salts [copper(II) citrate and copper(II) succinate] all increase solubility of the copper(II) salts. Relative increases in solubility follow the polarity trend in the selected amino acids, with serine creating the greatest increase in solubility. Simultaneous equilibria calculations indicate the formation of mixed-ligand complexes in the copper(II) succinate -amino acid systems, the first time such mixed-ligand complexes have been observed. In contrast, mixed-ligand complexes are not predicted in the copper(II) citrate -amino acid systems. Potential bioavailability of copper(II) appears to be increased by the inclusion of amino acids in solution, roughly in parallel with the increase in solubility of the copper(II) salt. Therefore, measurement of the change in solubility caused by addition of amino acids to aqueous solution gives qualitative insight to the potential increase in bioavailability of the metal ion.