Stabilizing Alginate Confinement and Polymer Coating of CO-Releasing Molecules Supported on Iron Oxide Nanoparticles To Trigger the CO Release by Magnetic Heating.

Abstract

Maghemite (Fe2O3) iron oxide nanoparticles (IONPs) were synthesized, modified with covalent surface-bound CO-releasing molecules of a tri(carbonyl)-chlorido-phenylalaninato-ruthenium(II) complex (CORM), and coated with a dextran polymer. The time- and temperature-dependent CO release from this CORM-3 analogue was followed by a myoglobin assay. A new measurement method for the myoglobin assay was developed, based on confining "water-soluble" polymer-coated Dextran500k@CORM@IONP particles in hollow spheres of nontoxic and easily prepared calcium alginate. Dropping a mixture of Dextran500k@CORM@IONP and sodium alginate into a CaCl2 solution leads to stable hollow spheres of Ca(2+) cross-linked alginate which contain the Dextran500k@CORM@IONP particles. This "alginate-method" (i) protects CORM-3 analogues from rapid CO-displacement reactions with a protein, (ii) enables a spatial separation of the CORM from its surrounding myoglobin assay with the alginate acting as a CO-permeable membrane, and (iii) allows the use of substances with high absorptivity (such as iron oxide nanoparticles) in the myoglobin assay without interference in the optical path of the UV cell. Embedding the CORM@IONP nanoparticles in the alginate vessel represents a compartmentation of the reactive component and allows for close contact with, yet facile separation from, the surrounding myoglobin assay. The half-life of the CO release from Dextran500k@CORM@IONP particles surrounded by alginate was determined to be 890 ± 70 min at 20 °C. An acceleration of the CO release occurs at higher temperature with a half-life of 172 ± 27 min at 37 °C and 45 ± 7 min at 50 °C. The CO release can be triggered in an alternating current magnetic field (31.7 kA m(-1), 247 kHz, 39.9 mT) through local magnetic heating of the susceptible iron oxide nanoparticles. With magnetic heating at 20 °C in the bulk solution, the half-life of CO release from Dextran500k@CORM@IONP particles decreased to 155 ± 18 min without a noticeable temperature increase in the dispersion. At 37 and 50 °C, the half-life for the CO release triggered by local magnetic heating was 65 ± 5 min and 30 ± 3 min, respectively. Thus, at a physiological temperature of 37 °C, magnetic heating accelerates the CO release of the IONP-bound CORM by a factor of ∼ 2.6. The activation energy for CO release from a CORM-3 analogue was determined to be EA = 78 kJ/mol.