Molecular interaction and partitioning in α-keratin using 1H NMR spin-lattice (T1) relaxation times.

The interactions between small molecules and keratins are poorly understood. In this paper, a nuclear magnetic resonance method is presented to measure changes in the 1H T1 relaxation times of small molecules in human hair keratin to quantify their interaction with the fibre. Two populations of small-molecule compounds were identified with distinct relaxation times, demonstrating the partitioning of the compounds into different keratin environments. The changes in relaxation time for solvent in hair compared with bulk solvent were shown to be related to the molecular weight (MW) and the partition coefficient, LogP, of the solvent investigated. Compounds with low MWs and high hydrophilicities had greater reductions in their T1 relaxation times and therefore experienced increased interactions with the hair fibre. The relative population sizes were also calculated. This is a significant step towards modelling the behaviour of small molecules in keratinous materials and other large insoluble fibrous proteins.

Metallostar Assemblies Based on Dithiocarbamates for Use as MRI Contrast Agents.

Two different octadentate gadolinium chelates based on DO3A and DOTAGA chelates (hydration number q = 1) have been used to prepare a series of bi-, tri-, and tetrametallic d-f mixed-metal complexes. The piperazine-based dithiocarbamate linker ensures that rotation of the gadolinium chelates is restricted, leading to enhanced relaxivity (r1) values, which increase with the overall mass and number of gadolinium units. The r1 value (at 10 MHz, 25 °C) per gadolinium unit rises from 5.0 mM-1 s-1 for the Gd-DO3A-NH2 monogadolinium chelate to 9.2 mM-1 s-1 in a trigadolinium complex with a ruthenium(III) core. Using a 1.5 T clinical scanner operating at 63.87 MHz (25 °C), an 86% increase in the relaxivity per gadolinium unit is observed for this multimetallic compound compared to clinically approved Dotarem. The gadolinium complexes based on the DOTAGA chelate also performed well at 63.87 MHz, with a relaxivity value of 9.5 mM-1 s-1 per gadolinium unit being observed for the trigadolinium d-f mixed-metal complex with a ruthenium(III) core. The versatility of dithiocarbamate coordination chemistry thus provides access to a wide range of d-f hybrids with potential for use as high-performance MRI contrast agents.

Polyfunctionalised Nanoparticles Bearing Robust Gadolinium Surface Units for High Relaxivity Performance in MRI.

The first example of an octadentate gadolinium unit based on DO3A (hydration number q=1) with a dithiocarbamate tether has been designed and attached to the surface of gold nanoparticles (around 4.4 nm in diameter). In addition to the superior robustness of this attachment, the restricted rotation of the Gd complex on the nanoparticle surface leads to a dramatic increase in relaxivity (r1 ) from 4.0 mm-1 s-1 in unbound form to 34.3 mm-1 s-1 (at 10 MHz, 37 °C) and 22±2 mm-1 s-1 (at 63.87 MHz, 25 °C) when immobilised on the surface. The one-pot synthetic route provides a straightforward and versatile way of preparing a range of multifunctional gold nanoparticles. The incorporation of additional surface units for biocompatibility (PEG and thioglucose units) and targeting (folic acid) leads to little detrimental effect on the high relaxivity observed for these non-toxic multifunctional materials. In addition to the passive targeting attributed to gold nanoparticles, the inclusion of a unit capable of targeting the folate receptors overexpressed by cancer cells, such as HeLa cells, illustrates the potential of these assemblies.