Tunable, Metal-Loaded Polydopamine Nanoparticles Analyzed by

Article pubs.acs.org/cm

Tunable, Metal-Loaded Polydopamine Nanoparticles Analyzed by Magnetometry Zhao Wang,†,§,∇ Yijun Xie,†,‡,∇ Yiwen Li,# Yuran Huang,†,‡ Lucas R. Parent,†,§,∥ Treffly Ditri,† Nanzhi Zang,†,‡,§ Jeffrey D. Rinehart,*,†,‡ and Nathan C. Gianneschi*,†,‡,§,∥,⊥ †

Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States ‡ Materials Science and Engineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States § Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States ∥ Department of Materials Science & Engineering, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States ⊥ Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States # College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China S Supporting Information *

ABSTRACT: We report the preparation and study of Mn(III)-, Fe(III)-, Co(II)-, Ni(II)-, Cu(II)-, Zn(II)-, and Ga(III)-loaded polydopamine nanoparticles (PDA-NPs) via autoxidation polymerization of metal−dopamine complexes in the presence of free dopamine. An analysis of the doping range and parameters that influence final particle morphology is presented. In addition, magnetometry provides a probe of the general electronic structure and electronic interactions for Mn(III)-, Ni(II)-, and Co(II)-loaded PDA-NPs. PDA-NPs doped with Mn(III) are found to have high spin, low anisotropy, and weak magnetic coupling and are therefore predicted to have superior relaxivity behavior compared to previously studied Fe(III)-loaded PDA-NPs. Comparison of Mn(III)- and Fe(III)-loaded PDA-NP relaxivity confirms the predictive ability of the magnetometry measurements.

M

elanins are a class of naturally occurring pigment found throughout nature. They have garnered much attention from chemists and materials scientists because of their range of functions in biology from metal ion chelation, photoprotection, free radical quenching, and coloration.1−3 Polydopamine (PDA), a commonly used synthetic melanin, reproduces key properties of natural melanin.4−6 For example, PDA displays a strong ability to chelate various metal ions, making it a promising material for a wide range of applications, including in bioimaging,7 surface modification,8 electrocatalysis,9,10 batteries,11 and in biosensing.12 A common approach to the preparation of metal-loaded PDA hybrid materials involves the synthesis of colloidal PDA nanoparticles (PDA-NPs), followed by doping with the appropriate metal salt (Figure 1). However, this methodology leads to limited metal loadings and is not compatible with metal ions with low water solubility, such as Mn(III).7,13 Recently, prepolymerization strategies were reported for the preparation of Fe(III)-loaded PDA-NPs in a single pot (Figure 1b).14,15 Despite these advances, the preparation of this class of materials with high and tunable metal loadings encompassing a variety of © 2017 American Chemical Society

Figure 1. Synthesis of PDA-NPs by (a) insertion of metal ions after polymerization (postpolymerization doping strategy) and (b) incorporation of metal ions during polymerization (prepolymerization doping strategy).

different metal ions beyond iron has remained a challenge. The interest in achieving this goal includes the fact that natural melanins chelate many metal ions and are involved in metal Received: June 1, 2017 Revised: August 1, 2017 Published: September 28, 2017 8195

DOI: 10.1021/acs.chemmater.7b02262 Chem. Mater. 2017, 29, 8195−8201

Article

Chemistry of Materials

possibly due to steric constraints on forming the tris-chelate within the cross-linked polymer network. A goal of this work was to screen for metal ions that are compatible with the formation of uniform particles via the prepolymerization strategy. This includes an investigation of how synthetic parameters such as reaction time, dopamine concentration, pH, and molar ratio of dopamine and metal salts affect the size and metal loading of the nanoparticles. To determine the versatility of this prepolymerization doping approach for the formation of spherical nanoparticles, a series of metal ions (Ti(IV), V(III), Cr(III), Mn(III), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), and Gd(III)) were examined, with all but Ti(IV), V(III), Cr(III), and Gd(III) found to be compatible. As an example of these reactions, dopamine hydrochloride and CuCl2·2H2O (Table S1) were fully dissolved in deionized water with stirring at room temperature for 1 h. Subsequently, tris(2-amino-2-hydroxymethylpropane-1,3-diol) aqueous solution was quickly injected into the established solution. After an additional 2 h of reaction, the targeted nanoparticles were separated by centrifugation and washed three times with deionized water. The Cu(II) variant was determined to form spherical nanoparticles by transmission electron microscopy (TEM) (Figure 2). Similarly, Mn(III)-,

remediation, and sequestration of potentially toxic metals as part of their function in humans and other animals.16,17 Synthetic systems could shed light on these complex polymeric materials, and their myriad functionalities in natural systems. We demonstrate the versatility of the synthetic approach through the preparation of PDA-NPs containing six different metal ions: Mn(III), Co(II), Ni(II), Cu(II), Zn(II), and Ga(III). Furthermore, the synthesis of Fe(III)-loaded PDANPs is discussed in detail to illustrate the reaction conditions necessary to tune particle size and the extent of metal loading. We find that the presence of Fe(III) cations increases the polymerization rate, which may be because of an increase in the concentration of reaction seed sites in solution. We optimized reaction conditions by tuning parameters (reaction time, dopamine concentration, and pH) to control particle size, yield, and percent metal loading. Our previous studies on Fe(III)-loaded PDA NPs utilized magnetometry to study the coordination environment and magnetic coupling strength between adjacent Fe(III) metal centers and elucidate the factors controlling magnetic resonance imaging (MRI) contrast ability of these materials.14 Importantly, it was concluded that antiferromagnetic coupling was hindering the contrast ratio at high loadings. In this work, we demonstrate how reduced magnetic couplings observed for Mn(III)-loaded PDA-NPs lead to a linear relationship between dopant concentration and MRI contrast ability.13 Furthermore, although difficult to quantify due to low moment, we find weak coupling and an S = 1 ground state from octahedrally coordinated Ni(II). Additionally, the Co(II)-doped sample shows evidence of strong single-ion anisotropy. These combined structural, electronic, oxidation state, and spin interaction data demonstrate the vast potential for magnetometry to describe metal coordination in complex, amorphous environments such as biomaterials. The complexation behavior between various metal ions and ligands containing ortho-dihydroxy moieties such as dopamine is well-established.18−21 Stable complexes featuring one, two, and three catecholate/metal binding interactions are observed at various pH values, with the extent of metal ligation often increasing with pH.22 To examine which metal can form complexes with dopamine ((M(DA)x) complexes) and then be subjected to use as a monomer to form metal-loaded PDA-NPs, a number of metals known to form stable complexes with catecholate ligands were surveyed, including Ti(IV), V(III), Cr(III), Mn(III), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Ga(III), and Gd(III).18,23,24 Solution phase complexation with dopamine could be monitored by UV−vis spectroscopy. For example, it is known that dopamine forms tris-complexes at basic pH with Fe(III).4,25 The presence of such complexes was confirmed by a strong absorption peak at 493 nm, which implied the presence of tris-dopamine−Fe(III) complexes within the solution.25 The amount of this complex in solution could be tuned in a facile manner by changing the amount of FeCl3·6H2O relative to the amount of dopamine (Figure S1). The concentration of tris-chelated Fe(III) significantly decreases as the amount of FeCl3·6H2O decreases, resulting in a large excess of free dopamine available for polymerization. The decrease in tris-chelation is accompanied by an increase in the intensity of the broad absorption between 500 and 700 nm, suggesting the formation of mono- and bis-dopamine−Fe(III) complexes. This synthetic method results in the formation of unsaturated mono- and bis-dopamine−Fe(III) complexes,

Figure 2. TEM images of metal-loaded PDA-NPs: (a) Mn(III)-1, (b) Co(II)-1, (c) Ni(II)-1, (d) Cu(II)-1, (e) Zn(II)-1, (f) Ga(III)-1.

Co(II)-, Ni(II)-, Zn(II)-, and Ga(III)-loaded PDA-NPs were prepared via this method (Table S1, Figure 2). Interestingly, these results show that varying metal ion identity has a significant influence on the size and uniformity of the resulting particles (Table S2 and Figure 2). For example, Zn(II)-loaded PDA-NPs exhibit the largest particle size (208 ± 30 nm), whereas Cu(II)-loaded PDA-NPs possess the smallest size (71 ± 12 nm). TEM images of these nanoparticles show the Ga(III)-loaded PDA-NPs have the most uniform spherical morphology, whereas the Co(II)-loaded PDA-NPs present a less uniform morphology. These differences may be attributed to different reaction kinetics caused by the metal−dopamine complex. The metal content in the nanoparticle can be controlled by the addition of different amounts of metal salt. At basic pH, tris and/or bis molecular metal−catecholate complexes are formed in solution. Therefore, the maximum molar ratio for the dopamine and metal salt is between 2:1 and 3:1, to ensure incorporation into the PDA-NPs. Table S1 shows conditions for adding dopamine to metal in the ratio of 2:1 or 3:1 capable of forming nanoparticles. Lower amounts of metal content in the final particle are easily accessible by adding lower amounts of metal salts, but increasing amounts result in 8196


Article


particles with metals incorporated via this route. We speculate these results might come from the different affinities and coordination geometries for dopamine and metal ions.26 The colloidal stability was investigated by measuring the zeta potential of all six samples. Table S2 shows that all samples exhibited highly negative zeta potential values, suggesting high stability in aqueous solution. In summary, the prepolymerization doping strategy allows access to metal contents more than 5 times greater than that of the postpolymerization doping strategy. To study the synthetic parameters that affect the size and metal content of the nanoparticles, we chose Fe(III)-loaded PDA-NPs since they can be formed as uniform spheres, with Fe(III) content critical to MRI performance. First, the effect of reaction time was studied by taking aliquots at a series of time points, followed by centrifugation and washing with deionized water. The morphology of the resulting NPs was then examined by TEM (Figure 4). Particle diameter as a function of reaction

aggregation of materials. Dark-field scanning transmission electron microscopy (STEM) and bright-field STEM show high contrast, suggesting the presence of metal inside the nanoparticles (Figure 3). STEM coupled with energy-dispersive

Figure 3. STEM-EDS analysis of Mn(III)-loaded PDA-NPs. (a) Darkfield STEM image of particles prior to EDS elemental mapping. (b) Bright-field STEM image of the region of interest used for mapping. (c−e) EDS elemental maps of the ROI for the characteristic X-ray emission peaks for (c) Al, (d) Mn, and (e) Cu. Al and Cu signals are background from the microscope column or sample holder/grid. Mn signal location overlays exclusively on the particles’ locations. (f) Raw EDS spectrum (summed over ROI), showing the clear Mn signal generated from the particles.

Figure 4. Representative TEM images of Fe(III)-loaded PDA-NPs quenched at different time points: (a) 15 min, (b) 30 min, (c) 45 min, (d) 60 min, (e) 120 min, (f) 240 min, (g) 360 min, (h) 480 min. (i) Reaction time versus particle diameter. (j) Reaction time versus particle yield. Particle yield is calculated by dividing the mass of collected particles by the mass of added monomer.

X-ray spectroscopy (EDS) further confirms the presence of Mn localized exclusively at the nanoparticles’ location (Figure 3d). The presence of Co and Ni was also confirmed by STEM-EDS analysis (Figures S3 and S4). Inductively coupled plasma-optical emission spectrometry (ICP-OES) was employed to determine the maximum achievable metal content (Table 1). The TEM images show Cu(II)-loaded PDA-NPs have less contrast compared with Zn(II)-loaded ones (Figure 2d,e), consistent with the lower metal content. In addition, we found that Ti(IV), V(III), Cr(III), and Gd(III) could not be used to generate spherical

time was analyzed showing that the size of a particle increases dramatically at the onset of polymerization, then reaches a plateau within 2 h (Figure 4i). After 2 h, decreased precursor concentration and a reduction in solution pH effectively stops the polymerization (Figure 4j).27 The yield of Fe(III)-loaded PDA-NPs was determined by measuring the dried mass of Fe(III)-loaded PDA-NPs and dividing by the original amount of dopamine/Fe(III). Notably, the plots of the extent of polymerization and particle size as a function of time are roughly similar in shape and both plateau around 2 h (Figure 4i,j), suggesting that the number of nanoparticles formed remains relatively fixed shortly after the onset of the polymerization. The formation of PDA-NPs in the absence of Fe(III) cations involves the oxidation of dopamine to 5,6dihydroxyindole (DHI), which, through various pathways, polymerizes to form PDA.28,29 It is suggested that the oxidation of dopamine is quite fast and polymerization is the ratedetermining step.30 This process requires a much longer time (∼12 h),6 indicating that the presence of Fe(III) ions significantly accelerates the speed of the reaction. To investigate whether the polymerization remains the rate-determining step in the presence of Fe(III), we propose a model in which PDANPs are spherical with identical radii. If the oxidation step is fast, the number of particles is constant during the polymerization, and the yield of spherical particles is then proportional to the volume of nanoparticle. A good linear fit is observed in plots of particle volume as a function of the reaction yield, thus confirming the assumption that the number of particles is

Table 1. Physical Parameters of Metal-Loaded PDA-NPs

a

sample

metal %a

synthetic strategy

Mn(III)-1 Co(II)-1 Ni(II)-1 Cu(II)-1 Zn(II)-1 Ga(III)-1 Mn(III)-2 Co(II)-2 Ni(II)-2 Cu(II)-2 Zn(II)-2 Ga(III)-2

9.6 9.6 13.4 8.0 17.2 13.2 0.1 0.4 0.7 0.4 0.8 2.4

predoping predoping predoping predoping predoping predoping postdoping postdoping postdoping postdoping postdoping postdoping

Weight percentage of metal in nanoparticles. 8197


Article


Previous reports on the polymerization of dopamine show that, at higher pH values, smaller PDA-NPs are formed.27 We next investigated whether or not this trend held true for polymerizations conducted in the presence of Fe(III) cations. In these studies, the dopamine concentration was held constant (1.6 mM) between runs and reactions were quenched after 6 h (Table S4). The size and morphology of the resulting nanoparticles were examined by TEM (Figure S6). Analogous to undoped PDA, the diameter of Fe(III)-loaded PDA nanoparticles decreases (350 to 70 nm) as the initial pH is raised (8.7 to 9.6), suggesting that the spontaneous autoxidation of dopamine is unaffected.27 Consequently, at higher pH values, the nucleation process of NPs is dominant, resulting in an increase in particle number with a concurrent decrease in particle size (Figure S7a). Interestingly, the Fe(III) content of the PDA-NPs was found to decrease as the initial pH was increased, which suggests that the influence of pH on the polymerization kinetics of Fe(III)-chelated and unchelated dopamine differs (Figure S7b). As follows, at higher pH values, the rate of polymerization of unchelated dopamine becomes comparable to that of Fe(III)-chelated dopamine, which in effect lowers the concentration of Fe(III) in the resulting PDANPs. The prepolymerization doping strategy affords access to a series of PDA-NPs featuring a number different metal ions with a much higher degree of metal loading than is possible for the postpolymerization doping strategy. Analysis by magnetometry was performed on a series of Ni(II)-, Co(II)-, and Mn(III)loaded PDA-NPs with different metal loadings to extract information about the spin-state and inter-ion interactions in this complex magnetic system. The various metal loadings were achieved by controlling the molar ratio of dopamine and metal salts (Table S5). In the cases of Ni(II)-loaded particles, magnetometry data were obtained for samples with 4.0, 5.4, 7.4, and 13.4% Ni(II) loading by mass (Figure 6a). For each sample, χMT is largely invariable with temperature. Only at very low temperatures are deviations seen, and these are likely due

constant during the polymerization (Figure S2a). Therefore, although the overall reaction speed is much faster with Fe(III) present than without, the polymerization is still the ratedetermining step. To gain further insight into the mechanistic role of the Fe(III) ion in the polymerization of dopamine, the concentration of Fe(III) in the NPs was monitored over the course of the polymerization. Again, ICP-OES was used to determine the Fe(III) concentration in the NPs at different time points. The feeding molar ratio of dopamine to the Fe(III) was 10:1 (3.5 wt % Fe(III) ion). Under these conditions, both chelated and unchelated dopamine are present in solution. Particles isolated at different time points show a decrease from 7.9 to 5.0 wt % Fe(III) (Figure S2b). This decrease indicates that the presence of Fe(III) ions enhances the polymerization rate of catechol to which it is directly coordinated. In our previous work,14 it was found that a sample with 5.86% Fe(III) loading exhibited the best in vitro MRI performance at a fixed particle concentration. To achieve this, a reaction time of 2 h was suggested. The formation of nanoparticles through the oxidative polymerization of dopamine is highly dependent on a number of parameters that influence the reaction kinetics.24,31 We first examined the effect dopamine concentrations have on particle size and Fe(III) content of the metal-loaded PDA-NP. These parameters are of interest because Fe(III) content directly affects MRI contrast and the overall size of the nanoparticle can significantly influence how it behaves in vivo.32 To exclude the interference of pH variations, shortly after the addition of the reactants, the initial pH was adjusted to be consistent between runs (Table S3). Reactions were quenched after 6 h, followed by examination of the resultant particle sizes and morphologies via TEM (Figure S5). Notably, very little particle formation was observed in reactions with dopamine concentrations below 1.1 mM. An initial dopamine concentration of 1.1 mM leads to average diameters as small as 112 nm. When the dopamine concentration was increased to 3.5 mM, a significant increase in particle diameter was observed (473 nm), which is consistent with PDA particle synthesis in the absence of Fe(III) cations.30 Importantly, dopamine concentrations greater than 3.5 mM result in significant cross-linking of the PDA nanoparticles. The reaction kinetics of the oxidative polymerization of dopamine suggests that the rate constant is directly proportional to the dopamine concentration as reflected by the larger particle size at higher concentrations (Figure 5a). Additionally, the initial

Figure 5. (a) Dopamine concentration (mM) versus particle diameter (nm). (b) Initial dopamine concentration versus wt % Fe(III) loading. Figure 6. Temperature dependence of the product of magnetic susceptibility and temperature (χMT) for (a) Ni(II)-, (b) Co(II)-, and (c) Mn(III)-loaded PDA-NPs. Susceptibility data for Mn(III)-loaded particles are globally fit using eq 1 (J = −1.97 cm−1; g = 2). (d) Dependence of per-particle relaxivity on the wt % of Mn(III) or Fe(III) demonstrating the effect of reduced antiferromagnetic coupling strength on MRI contrast ability.

dopamine concentration has no perceivable influence on the Fe(III) content of the resulting NPs, suggesting that dopamine concentration alters the rate of polymerization of Fe(III)chelated and unchelated dopamine to a similar degree (Figure 5b). 8198


Article


The magnetic resonance (MR) relaxivity of Mn(III)- and Fe(III)-loaded PDA-NPs was measured using a Bruker 7.0 T magnet. T1-weighted MR images of Mn(III)-loaded PDA-NPs demonstrate that contrast increases monotonically with particle concentrations (Figure S9). The r1 relaxivities of Mn(III)-1, 2, 3, and 4 were 4.7, 5.8, 8.2, and 8.3 mM−1 s−1, respectively (Figure S10 and Table S6), which are relatively high values among the reported relaxivities of the nanoparticle T1-weighted contrast agents at high magnetic field strengths.13,14,37,38 The attenuated T1 signal of Mn(III)-1 at the highest concentration seems to result from the T1 signal saturation since the T2 effects of the contrast agent will start to dominate the signal behavior.39,40 The r2/r1 ratios of these nanoparticles were 8.2, 10.6, 13.8, and 13.5, respectively (Table S6), demonstrating that Mn(III)-doped PDA nanoparticles could be used as T1 contrast agents. Similar to our previous work,14 “per particlerelaxivity” (r1p(particle)) was also used to determine the relaxivity with respect to a single particles, which can be calculated by multiplying metal ion wt % per particle by the per-metal ions relaxivity value (r1p(ion)). Comparing the relaxivity value of Mn(III) with Fe(III), it was clearly observed that Mn(III)loaded PDA-NPs show significantly higher r1p(ion) and r1p(particle) values compared to Fe(III) samples (Figure 6d, Figure S11). This enhancement is approximately 100% when adjusted for the spin of Fe(III) (S = 5/2) versus Mn(III) (S = 2). Additionally, r1p(particle) of Mn(III)-loaded PDA-NPs displays an almost linear increase from 1.7 to 8.2 with the increase of Mn(III) concentration, while r1p(particle) of the Fe(III) data saturates at a relatively low Fe(III) weigh percent of 5.86%, suggesting that Mn(III)-loaded PDA-NPs have enhanced performance as MRI contrast agent compared with Fe(III)loaded PDA-NPs (Figure 6d). These factors directly follow from the loss of unpaired spin due to the stronger antiferromagnetic coupling in Fe(III) compared to Mn(III) centers. These results not only demonstrate the superior contrast of Mn(III)-doped PDA-NPs but also show how a simple magnetometry analysis can be used to discover optimum contrast materials prior to extensive MR analysis. In conclusion, we have prepared various kinds of metalloaded PDA-NPs via a copolymerization strategy. The polymerization is found to be accelerated by the presence of the metal dopamine complex. The marked increase in metal loading afforded by this approach when compared to standard postpolymerization doping strategies provides a means to study structural information on PDA materials. Our study of Ni(II)and Co(II)-loaded PDA-NPs has demonstrated how a simple magnetometry analysis can extract average magnetic structural information from an exceedingly complex, disordered magnetic system. The magnetometry and MRI studies of Fe(III)- and Mn(III)-loaded PDA-NPs confirm that controlling and diminishing antiferromagnetic coupling between Mn(III) centers enhances their performance as MRI contrast agents. From a general materials standpoint, synthetic access to a variety of highly doped PDA-based systems will have an impact on how these materials are optimized and assessed for performance in myriad applications from MRI, to electrocatalysis and battery materials.

to weak zero-field splitting effects rather than antiferromagnetic coupling as they do not scale with Ni(II) loading. The absolute value of χMT is seen to vary erratically for the different Ni(II) loadings, likely due to the small spin (S = 1) and hygroscopic nature of the Ni(II)-complexed particles.33 Overall, this prevents quantitative interpretation of the data, but we can still infer that all samples are Ni(II) in a roughly octahedral environment with very weak exchange coupling. Samples predoped with 5.5% and 9.6% Co(II) show a room temperature χMT value of 2 emu·K/cm−3 that gradually decays to 1 emu·K/cm−3 at 2 K, consistent with an S = 3/2 Co(II) ion with considerable unquenched orbital moment (Figure 6b). While this curvature in χMT could also be the result of antiferromagnetic exchange coupling, this is unlikely since it is independent of Co(II) ion concentration. Unexpectedly, the lowest Co(II) concentration (2.0%) has a much higher overall χMT value over the entire temperature range. This could be the result of either variation in solvent mass as in the Ni(II) case, or the presence of a population of further oxidized (S = 2) Co(III) ions in this sample. In addition, the tunable loading of paramagnetic metal ions provides a means to optimize metal-loaded PDA-NPs for T1weighted MR contrast. We anticipated that the low anisotropy and high moment (S = 2) of Mn(III) could provide an interesting comparison to our previously studied Fe(III) MR contrast agents. In our previous work, magnetometry was shown to be an effective tool for evaluating the factors that control MRI contrast ability of Fe(III)-loaded PDA-NPs.14 Importantly, the predoping strategy allows for the preparation of previously inaccessible metal-loaded PDA-NPs through the formation of soluble metal−dopamine complexes. We prepared a series of Mn(III)-doped PDA-NPs containing varying degrees of Mn(III) loading (Mn(III)-i; i = 1−4), where Mn(III)-1 represented the NPs with the highest achievable loading (9.6 wt %) using our methods (Figure S8). The magnetic properties of Mn(III)-doped PDA-NPs were first investigated by variabletemperature magnetic susceptibility measurements from 2 to 300 K under a 5000 Oe magnetic field (Figure 6c). Significantly, there is no appreciable deviation of χMT for the Mn(III)-i samples as temperature is decreased, which is in contrast to our reported Fe(III) data, indicating that antiferromagnetic superexchange interactions between adjacent Mn(III) are far weaker than those observed between Fe(III) cations. This is consistent with a coupling pathway that is weakened through the Mn(III) d4 Jahn−Teller distortion. The model constructed to analyze Fe(III) interactions, incorporating an isotropic g value and magnetic coupling constant (J), was used to analyze the magnetic properties of Mn(III) in the PDA NPs. In this model, two types of Mn(III) centers are considered: magnetically isolated Mn(III) and magnetically coupled Mn(III) centers. A global fitting of susceptibility data was performed wherein both magnetically isolated (ideal S = 2 paramagnet), and magnetically coupled Mn(III) were included. Magnetic coupling was modeled through an HDVV Hamiltonian term (eq 1) Ĥ = −2JMn−Mn S1·̂ S2 ̂

■

(1)

where S1 ̂ and S2 ̂ are spin operators for equivalent interacting spins. A J value (−1.1 cm−1) was demonstrated which was significantly smaller than the Fe(III)-catechol structure (−24.8 cm−1),14,34−36 indicating the limited antiferromagnetic interaction of Mn(III).

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.chemmater.7b02262. 8199


Article


■

General methods, UV−visible absorption spectra, fitting curve of particle volume vs yield, curve of reaction time vs Fe(III) weight percent, STEM-EDS analyses, table of reactants and their formulations data, table of size and zeta potential data, pH vs particle diameter, pH vs Fe(III) loading, TEM images, T1-weighted MR images, T1 MRI relaxivity plots, table of MR relaxivity results, and r1 relaxation rates per weight percent plots (PDF)

(8) Lee, B. P.; Messersmith, P. B.; Israelachvili, J. N.; Waite, J. H. Mussel-Inspired Adhesives and Coatings. Annu. Rev. Mater. Res. 2011, 41, 99−132. (9) Zhou, D.; Yang, L.; Yu, L.; Kong, J.; Yao, X.; Liu, W.; Xu, Z.; Lu, X. Fe/N/C hollow nanospheres by Fe(iii)-dopamine complexationassisted one-pot doping as nonprecious-metal electrocatalysts for oxygen reduction. Nanoscale 2015, 7, 1501−1509. (10) Ai, K.; Liu, Y.; Ruan, C.; Lu, L.; Lu, G. Sp2 C-Dominant NDoped Carbon Sub-micrometer Spheres with a Tunable Size: A Versatile Platform for Highly Efficient Oxygen-Reduction Catalysts. Adv. Mater. 2013, 25, 998−1003. (11) Yao, X.; Zhao, C.; Kong, J.; Wu, H.; Zhou, D.; Lu, X. Dopamine-assisted one-pot synthesis of zinc ferrite-embedded porous carbon nanospheres for ultrafast and stable lithium ion batteries. Chem. Commun. 2014, 50, 14597−14600. (12) Liu, Y.; Ai, K.; Lu, L. Polydopamine and Its Derivative Materials: Synthesis and Promising Applications in Energy, Environmental, and Biomedical Fields. Chem. Rev. 2014, 114, 5057−5115. (13) Miao, Z.-H.; Wang, H.; Yang, H.; Li, Z.-L.; Zhen, L.; Xu, C.-Y. Intrinsically Mn2+-Chelated Polydopamine Nanoparticles for Simultaneous Magnetic Resonance Imaging and Photothermal Ablation of Cancer Cells. ACS Appl. Mater. Interfaces 2015, 7, 16946−16952. (14) Li, Y.; Xie, Y.; Wang, Z.; Zang, N.; Carniato, F.; Huang, Y.; Andolina, C. M.; Parent, L. R.; Ditri, T. B.; Walter, E. D.; Botta, M.; Rinehart, J. D.; Gianneschi, N. C. Structure and Function of IronLoaded Synthetic Melanin. ACS Nano 2016, 10, 10186−10194. (15) Ang, J. M.; Du, Y.; Tay, B. Y.; Zhao, C.; Kong, J.; Stubbs, L. P.; Lu, X. One-Pot Synthesis of Fe(III)−Polydopamine Complex Nanospheres: Morphological Evolution, Mechanism, and Application of the Carbonized Hybrid Nanospheres in Catalysis and Zn−Air Battery. Langmuir 2016, 32, 9265−9275. (16) Hong, L.; Simon, J. D. Current Understanding of the Binding Sites, Capacity, Affinity, and Biological Significance of Metals in Melanin. J. Phys. Chem. B 2007, 111, 7938−7947. (17) Simpson, M. J.; Wilson, J. W.; Robles, F. E.; Dall, C. P.; Glass, K.; Simon, J. D.; Warren, W. S. Near-Infrared Excited State Dynamics of Melanins: The Effects of Iron Content, Photo-Damage, Chemical Oxidation, and Aggregate Size. J. Phys. Chem. A 2014, 118, 993−1003. (18) Sever, M. J.; Wilker, J. J. Visible absorption spectra of metalcatecholate and metal-tironate complexes. Dalton Trans. 2004, 1061− 1072. (19) Ejima, H.; Richardson, J. J.; Liang, K.; Best, J. P.; van Koeverden, M. P.; Such, G. K.; Cui, J.; Caruso, F. One-Step Assembly of Coordination Complexes for Versatile Film and Particle Engineering. Science 2013, 341, 154−157. (20) Rahim, M. A.; Björnmalm, M.; Bertleff-Zieschang, N.; Besford, Q.; Mettu, S.; Suma, T.; Faria, M.; Caruso, F. Rust-Mediated Continuous Assembly of Metal−Phenolic Networks. Adv. Mater. 2017, 29, 1606717. (21) Rahim, M. A.; Björnmalm, M.; Suma, T.; Faria, M.; Ju, Y.; Kempe, K.; Müllner, M.; Ejima, H.; Stickland, A. D.; Caruso, F. Metal−Phenolic Supramolecular Gelation. Angew. Chem., Int. Ed. 2016, 55, 13803−13807. (22) Holten-Andersen, N.; Harrington, M. J.; Birkedal, H.; Lee, B. P.; Messersmith, P. B.; Lee, K. Y. C.; Waite, J. H. pH-induced metal-ligand cross-links inspired by mussel yield self-healing polymer networks with near-covalent elastic moduli. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 2651−2655. (23) Srivastava, T. N.; Mohan, G. Complex Compounds of Ga(III) and In(III) with Catechol. Z. Anorg. Allg. Chem. 1970, 379, 82−87. (24) Freeman, G. E.; Raymond, K. N. Specific sequestering agents for the actinides. 12. Synthetic and structural chemistry of gadolinium and holmium catecholates. Inorg. Chem. 1985, 24, 1410−1417. (25) Charkoudian, L. K.; Franz, K. J. Fe(III)-Coordination Properties of Neuromelanin Components: 5,6-Dihydroxyindole and 5,6-Dihydroxyindole-2-carboxylic Acid. Inorg. Chem. 2006, 45, 3657−3664. (26) Hider, R. C.; Kong, X. Chemistry and biology of siderophores. Nat. Prod. Rep. 2010, 27, 637−657.

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (J.D.R.). *E-mail: [email protected] (N.C.G.). ORCID

Yiwen Li: 0000-0002-6874-0350 Nathan C. Gianneschi: 0000-0001-9945-5475 Author Contributions ∇

These authors contributed equally to this work.

Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS The authors acknowledge the generous support of this research from AFOSR. TEM analysis of materials was conducted at the UCSD Cryo-Electron Microscopy Facility, supported by NIH funding to Dr. Timothy S. Baker and the Agouron Institute gifts to UCSD. TEM-EDS was performed in the EPIC facility of Northwestern University’s NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the MRSEC program (NSF DMR-1121262) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. LRP is supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under award number F32EB021859.

■

REFERENCES

(1) Simon, J. D.; Peles, D. N. The Red and the Black. Acc. Chem. Res. 2010, 43, 1452−1460. (2) Meredith, P.; Sarna, T. The physical and chemical properties of eumelanin. Pigm. Cell Res. 2006, 19, 572−594. (3) Simon, J. D. Spectroscopic and Dynamic Studies of the Epidermal Chromophores trans-Urocanic Acid and Eumelanin. Acc. Chem. Res. 2000, 33, 307−313. (4) Paris, I.; Martinez-Alvarado, P.; Perez-Pastene, C.; Vieira, M. N. N.; Olea-Azar, C.; Raisman-Vozari, R.; Cardenas, S.; Graumann, R.; Caviedes, P.; Segura-Aguilar, J. Monoamine transporter inhibitors and norepinephrine reduce dopamine-dependent iron toxicity in cells derived from the substantia nigra. J. Neurochem. 2005, 92, 1021−1032. (5) Xiao, M.; Li, Y.; Zhao, J.; Wang, Z.; Gao, M.; Gianneschi, N. C.; Dhinojwala, A.; Shawkey, M. D. Stimuli-Responsive Structurally Colored Films from Bioinspired Synthetic Melanin Nanoparticles. Chem. Mater. 2016, 28, 5516−5521. (6) Xiao, M.; Li, Y.; Allen, M. C.; Deheyn, D. D.; Yue, X.; Zhao, J.; Gianneschi, N. C.; Shawkey, M. D.; Dhinojwala, A. Bio-Inspired Structural Colors Produced via Self-Assembly of Synthetic Melanin Nanoparticles. ACS Nano 2015, 9, 5454−5460. (7) Ju, K.-Y.; Lee, J. W.; Im, G. H.; Lee, S.; Pyo, J.; Park, S. B.; Lee, J. H.; Lee, J.-K. Bio-Inspired, Melanin-Like Nanoparticles as a Highly Efficient Contrast Agent for T1-Weighted Magnetic Resonance Imaging. Biomacromolecules 2013, 14, 3491−3497. 8200


Article

Chemistry of Materials (27) Ho, C.-C.; Ding, S.-J. The pH-controlled nanoparticles size of polydopamine for anti-cancer drug delivery. J. Mater. Sci.: Mater. Med. 2013, 24, 2381−2390. (28) Hong, S.; Na, Y. S.; Choi, S.; Song, I. T.; Kim, W. Y.; Lee, H. Non-Covalent Self-Assembly and Covalent Polymerization CoContribute to Polydopamine Formation. Adv. Funct. Mater. 2012, 22, 4711−4717. (29) Dreyer, D. R.; Miller, D. J.; Freeman, B. D.; Paul, D. R.; Bielawski, C. W. Elucidating the Structure of Poly(dopamine). Langmuir 2012, 28, 6428−6435. (30) Ju, K.-Y.; Lee, Y.; Lee, S.; Park, S. B.; Lee, J.-K. Bioinspired Polymerization of Dopamine to Generate Melanin-Like Nanoparticles Having an Excellent Free-Radical-Scavenging Property. Biomacromolecules 2011, 12, 625−632. (31) Ball, V.; Frari, D. D.; Toniazzo, V.; Ruch, D. Kinetics of polydopamine film deposition as a function of pH and dopamine concentration: Insights in the polydopamine deposition mechanism. J. Colloid Interface Sci. 2012, 386, 366−372. (32) Estelrich, J.; Sánchez-Martín, M. J.; Busquets, M. A. Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents. Int. J. Nanomed. 2015, 10, 1727. (33) Brückner, C.; Caulder, D. L.; Raymond, K. N. Preparation and Structural Characterization of Nickel(II) Catecholates. Inorg. Chem. 1998, 37, 6759−6764. (34) Grillo, V. A.; Hanson, G. R.; Wang, D.; Hambley, T. W.; Gahan, L. R.; Murray, K. S.; Moubaraki, B.; Hawkins, C. J. Synthesis, X-ray Structural Determination, and Magnetic Susceptibility, Mössbauer, and EPR Studies of (Ph4P)2 [Fe2(Cat)4(H2O)2]·6H2O, a CatecholatoBridged Dimer of Iron(III). Inorg. Chem. 1996, 35, 3568−3576. (35) Gorun, S. M.; Lippard, S. J. Magnetostructural correlations in magnetically coupled (.mu.-oxo)diiron(III) complexes. Inorg. Chem. 1991, 30, 1625−1630. (36) Taylor, S. W.; Chase, D. B.; Emptage, M. H.; Nelson, M. J.; Waite, J. H. Ferric Ion Complexes of a DOPA-Containing Adhesive Protein from Mytilus edulis. Inorg. Chem. 1996, 35, 7572−7577. (37) Huang, J.; Xie, J.; Chen, K.; Bu, L.; Lee, S.; Cheng, Z.; Li, X.; Chen, X. HSA coated MnO nanoparticles with prominent MRI contrast for tumor imaging. Chem. Commun. 2010, 46, 6684−6686. (38) Kim, T.; Momin, E.; Choi, J.; Yuan, K.; Zaidi, H.; Kim, J.; Park, M.; Lee, N.; McMahon, M. T.; Quinones-Hinojosa, A.; Bulte, J. W. M.; Hyeon, T.; Gilad, A. A. Mesoporous Silica-Coated Hollow Manganese Oxide Nanoparticles as Positive T1 Contrast Agents for Labeling and MRI Tracking of Adipose-Derived Mesenchymal Stem Cells. J. Am. Chem. Soc. 2011, 133, 2955−2961. (39) Bjørnerud, A. The Physics of Magnetic Resonance Imaging; FYSKJM 4740 Lecture Notes; University of Oslo: Oslo, Norway, 2008. (40) Kim, B. H.; Lee, N.; Kim, H.; An, K.; Park, Y. I.; Choi, Y.; Shin, K.; Lee, Y.; Kwon, S. G.; Na, H. B.; Park, J.-G.; Ahn, T.-Y.; Kim, Y.-W.; Moon, W. K.; Choi, S. H.; Hyeon, T. Large-Scale Synthesis of Uniform and Extremely Small-Sized Iron Oxide Nanoparticles for HighResolution T1Magnetic Resonance Imaging Contrast Agents. J. Am. Chem. Soc. 2011, 133, 12624−12631.

8201


Tunable, Metal-Loaded Polydopamine Nanoparticles Analyzed by

Recommend Documents