SUPPLEMENTARY MATERIAL

Rui Zhang,† Benjamin Fellows,‡ Nikorn Pothayee,*§ Nan Hu,† Nipon Pothayee,† Ami Jo,† Ana C.

Bohórquez,∥ Carlos Rinaldi,∥ Olin Thompson Mefford,‡ Richey M. Davis† and Judy S. Riffle*†

†Department of Chemistry, Department of Chemical Engineering, and Macromolecules

Innovation Institute, Virginia Tech, Blacksburg, VA 24061

‡Department of Materials Science and Engineering and the Center for Optical Materials Science

and Engineering (COMSET), Clemson University, Clemson, SC 29634

§Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders

and Stroke, National Institutes of Health, Bethesda, MD 20892

∥J. Crayton Pruitt Family Department of Biomedical Engineering and Department of Chemical

Engineering, University of Florida, Gainesville, FL 32611

*Corresponding Author E-mail: jriffle@vt.edu

The experimental setup for calorimetric measurements is shown in Fig. S1. Data was

collected using an EasyHeat Induction Heating System produced by Ameritherm. The five-turn

induction coil contained a polycarbonate recirculating water bath designed to regulate sample

temperature. The temperature changes in each sample were measured using a fiber optic

temperature sensor from NeoptixTM. The sample was allowed to reach thermal equilibrium prior

to turning on the magnetic field. Temperature was recorded every five seconds. Measurements

were conducted at a frequency of 205 kHz and a magnetic field strength of 30 kA m -1 that was

verified using an AC field probe (AMF Life Science). The hexyl MGICs dispersion (3.5 mg mL-

1, 0.5 mL) was used to measure the heating rate. The SAR of the MGICs was calculated from its

heat capacity (C), the initial slope of the temperature versus time curve (ΔT/Δt, K s -1), and the

total mass of the MGICs dispersion, divided by the mass of iron as determined from ICP-AES.

[1]

Fig. S1 Experimental setup for calorimetric measurements

Synthetic methods for the monomers as well as the graft copolymers have been described in

our previous papers.[2, 3] The synthetic scheme for the hexylamino bisphosphonate methacrylate

monomer is shown in Fig. S2. The propylamino bisphosphonate methacrylate monomer can be

prepared by the same procedure, by using 3-amino-1-propanol instead of 6-amino-1-hexanol.

The acrylate-functional PEO oligomer was synthesized by reacting a commercial ~5000 Mn

poly(ethylene oxide) monomethyl ether with freshly-distilled acryloyl chloride.

Fig. S2 Synthesis of hexylamino bisphosphonate methacrylate monomer

Conventional free radical polymerization was utilized to synthesize the graft copolymers.

The phosphonate esters were then selectively hydrolyzed without affecting the carboxylic esters

by a mild approach previous reported by our group. The synthetic scheme for the polymerization

and selective hydrolysis is shown in Fig. S3.

Fig. S3 Synthesis of poly(hexyl ammonium bisphosphonic acid methacrylate)-g-PEO

copolymers

1H and 31P NMR spectra of the poly(propyl ammonium bisphosphonate methacrylate)-g-

PEO before and after phosphonate ester hydrolysis are shown in Fig. S4 and S5. The poly(hexyl

ammonium bisphosphonate methacrylate)-g-PEO had similar spectra. Due to solubility issues,

the graft copolymers before and after selective hydrolysis were analyzed in different deuterated

solvents. The 1H NMR spectra featured the disappearance of protons corresponding to the methyl

and methylene groups of the phosphonate esters (peaks h and i in the top spectrum in Fig. S4).

The methyl protons (peak i) had a chemical shift at ~1.3 ppm, and this peak completely

disappeared after hydrolysis. The methylene protons on the phosphonate esters (peak h) had a

chemical shift of 4 ppm, very close to the methylene proton resonance on the carboxylic ester of

the bisphosphonate graft segment (peak c). Before hydrolysis, peaks c and h combined indicated

that 10 Hs per phosphonate monomer unit were present. After selective hydrolysis, only 2 Hs

remained due to the carboxylic ester methylene. This was confirmed by the integrals in the

spectra. The protons on the poly(ethylene oxide) segment (peaks l and m) remained unchanged,

indicating that the carboxylic esters on the PEO segment were not affected by the hydrolysis

procedure. The spectra indicated that the phosphonate esters had been selectively deprotected,

with little to no effects on the carboxylic esters. 31P NMR spectra (Fig. S5) further demonstrated

the success of the removal of the phosphonate esters. The single phosphorus resonance shifted

from 31 to 16 ppm, which was in good agreement with our previous study with polymer end

groups.[2]

Fig. S4 1H NMR spectra show successful deprotection of the phosphonate esters of the

poly(propyl ammonium bisphosphonate methacrylate)-g-PEO copolymers with minimal effect

on carboxylic esters

Fig. S5 31P NMR spectra of the poly(propyl ammonium bisphosphonate methacrylate)-g-PEO

The 1H NMR spectrum of the PEO-g-PAA is shown in Fig. S6. The integrals indicated that

there were ~75 acrylate repeat units per PEO graft. Based on this, the graft copolymer contained

about 50 wt% of PEO and 50 wt% of poly(sodium acrylate).

Fig. S6 1H NMR spectrum of the PEO-g-PAA

Fig. S7 Additional representative images of MGICs following complexation with copolymers

that led to a cluster formation.

[1] E. C. Vreeland, J. Watt, G. B. Schober, et al., "Enhanced Nanoparticle Size Control by Extending LaMer’s Mechanism," Chemistry of Materials, vol. 27, no. 17, pp. 6059-6066, 2015.[2] N. Hu, L. M. Johnson, N. Pothayee, et al., "Synthesis of ammonium bisphosphonate monomers and polymers," Polymer, vol. 54, no. 13, pp. 3188-3197, 2013.[3] N. Pothayee, N. Pothayee, N. Hu, et al., "Manganese graft ionomer complexes (MaGICs) for dual imaging and chemotherapy," Journal of Materials Chemistry B, vol. 2, no. 8, pp. 1087-1099, 2014.