# Synthesis, Characterization, and Magnetic Properties of Fe(BIP)3, a Novel Paramagnetic Relaxation Agent

## TL;DR

This paper introduces a new iron-based compound that could serve as a safer alternative to traditional contrast agents used in MRI scans.

## Contribution

The study presents a novel paramagnetic relaxation agent based on a homoleptic diketonate Fe3+ complex with biocompatible indole moieties.

## Key findings

- Fe(BIP)3 spontaneously forms nanoscale aggregates in water with a hydrodynamic radius of about 30 nm.
- The compound shows high transverse relaxivity (r2 = 52.3 mM−1s−1), indicating strong potential as a contrast agent.
- Incorporation into phospholipid vesicles improves the stability of Fe(BIP)3 aggregates.

## Abstract

Background/Objectives: First row transition metal ions have recently regained attention in coordination chemistry as alternatives to gadolinium-based paramagnetic contrast agents, motivated by emerging safety concerns associated with certain Gd3+-based contrast agents. In this study, we report the development of a novel homoleptic diketonate Fe3+ complex functionalized with biocompatible indole moieties. We investigate its potential as a paramagnetic relaxation agent by evaluating its ability to modulate the T1 and T2 relaxation times of water proton. Methods: Iron(III) tris-1,3-(1-methylindol-3-yl)propanedionate [Fe(BIP)3] was synthesized via a thermal method from bis(1-methylindol-3-yl)-1,3-propanedione (HBIP) using Fe(ClO4)3∙6 H2O as the metal source. The complex was characterized by UV-Vis, IR and NMR spectroscopy, differential scanning calorimetry–thermogravimetric analysis, and single-crystal X-ray diffraction. Fe(BIP)3 aggregation behavior in aqueous environment, including size and morphology of aggregates, was investigated using dynamic light scattering and scanning electron microscopy. Incorporation of the aggregates into phospholipid vesicles was evaluated by fluorescence resonance energy transfer and fluorescence correlation spectroscopy. The paramagnetic properties of monomeric Fe(BIP)3 were probed in solution by nuclear magnetic resonance recurring to the Evans bulk magnetization method. Results: The designed synthetic procedure successfully afforded Fe(BIP)3, which was fully characterized by UV-Vis and IR spectroscopy, as well as single-crystal X-ray diffraction. Aqueous solutions of Fe(BIP)3 spontaneously formed rice-grain-shaped nanoscale aggregates of hydrodynamic radius ≈ 30 nm. Incorporation of these aggregates into phospholipid vesicles enhanced their stability. The longitudinal r1 and transverse r2 relaxivities of Fe(BIP)3 aggregates were assessed to be 1.92 and 52.3 mM−1s−1, respectively, revealing their potential as paramagnetic relaxation agents. Conclusions: Fe(BIP)3 aggregates, stabilized through incorporation into phospholipid vesicles, demonstrate promising potential as novel paramagnetic relaxation agents in aqueous environments.