UC San Diego

Melanins are a class of naturally occurring pigments found throughout nature. They have gained great attention because it has a unique combination of properties functions from metal ion chelation, photoprotection, free radical quenching, and coloration. We apply the synthetic chemistry combined with our increasing understanding of the natural systems to target, control, combine, and enhance the functionality of natural melanin, far beyond their natural capabilities. We term these nanostructures “Artificial Melanin”. Polydopamine (PDA), one type of synthetic melanin, reproduces essential properties of natural melanin. For example, PDA displays a keen ability to chelate various metal ions, making it a promising material for a wide range of applications, including in bioimaging, surface modification, electrocatalysis, batteries, and biosensing. We demonstrate that the introduction of metal to PDA can allow us to understand the effect of the spin centers towards the magnetic relaxation properties of a surrounding medium. These findings offer a guide to design more efficient contrast agents.

For Chapter 2, we employ a synthetic method for drastically increasing and controlling the iron loading of artificial melanin particles to perform a quantitative investigation on the structure-property relationship by using a family of Fe(III)-chelated polydopamine nanoparticles doped with a tunable concentration of Fe(III) ions. A comprehensive analysis by magnetometry, electron paramagnetic resonance (EPR), and nuclear magnetic resonance dispersion (NMRD) demonstrates that the population of isolated Fe(III) centers dictates the degree of MRI contrast. These analyses allow prediction of the optimal Fe(III) loading via a quantitative modeling of antiferromagnetic coupling. These conclusions not only offer an intuitive understanding of the atomic origins of MRI contrast in complex polycatechol nanoparticles but also suggest future directions for the development of new enhanced MRI contrast agents.

For Chapter 3, we synthesize metal-loaded polydopamine nanoparticles via autoxidation polymerization of dopamine in the presence of metal-dopamine complexes. Various metal ions including Mn(III), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), and Ga(III) ions could be incorporated into these artificial melanin nanoparticles with this strategy. We perform analysis on the doping range and parameters that affect the particles’ morphology. An investigation by magnetometry reveals general electronic structure and interactions for artificial melanin nanoparticles doped with Mn(III), Ni(II) and Co(II) ions. In addition, we compare the magnetic properties of high Mn(III)-loaded nanoparticles with Fe(III)-loaded nanoparticles to assess their potential as MRI contrast agents.

For Chapter 4, we report the preparation artificial melanin nanoparticles with tunable Gadolinium loadings. These nanoparticles are analyzed by NMRD and with a 7 T magnetic resonance imaging (MRI) scanner. We observed a relaxivity of 75 mM−1 s −1 and 10.3 mM−1 s −1 at 1.4 T and 7 T, respectively. Furthermore, we examined intraparticle magnetic interactions using Superconducting Quantum Interference Device (SQUID) magnetometry and determine these nanoparticles consist of isolated Gd ions even at the maximum metal loadings. This study shows the potential of this scaffold as a basis for developing T1- weighted, high relaxivity MRI contrast agents.

For Chapter 5, we report the preparation of norborenyl cyclic elastin-like polypeptides based homopolymers and amphiphilic block copolymers via ring opening metathesis polymerization. The resulting materials contain side chains that can undergo conformational and topological changes upon heating and treatment with a proteolytic enzyme. This work demonstrates that by incorporating a cyclic form of a peptide into a polymer as a functional sidechain, one can access a new mode of action regarding the enzymatic stimulus.