ATP-responsive Mn(ii)-based T1 contrast agent for MRI

A novel diacetylpyridylcarbohydrazide–DAPyCOHz-based manganese(ii) chelate with dipicolylamine/zinc(ii) (DPA/Zn2+) arms (MnLDPA-Zn2) was developed for adenosine triphosphate (ATP) responsive magnetic resonance imaging (MRI) T1 contrast applications. Compound 2 shows enhanced relaxivity (r1 = 11.52 mM−1 s−1) upon selective ATP binding over other phosphates.


Experimental Procedures
Figs. S1-S4 1 H, 13 C NMR and Electrospray-Mass spectral profiles of compounds DPACOHz, MnL DPA  (1) and MnL DPA-Zn (2).Table S1.Selected best-fit parameters obtained from the analysis of the Relaxometry and absorption spectral titration data of 1 and 2 and their Zn 2+ and sodium salts of Pi, PPi, AMP, ADP, and ATP complexes.

References
Electronic Supplementary Material (ESI) for Chemical Communications.This journal is © The Royal Society of Chemistry 2023

Materials and Measurements
The precursor compound 2-(bis(pyridin-2-ylmethyl)amino)acetohydrazide (DPACOHz) was synthesised by employing a slightly modified literature-reported procedure. 1All materials and reagents for synthesising Mn 2+ (1 and 2) complexes were purchased from Sigma-Aldrich (Dorset, UK) and used without further purification.Solvents were purchased from VWR (Leicestershire, UK).IR spectra were recorded on a Perkin Elmer Rx FTIR x2 with diamond ATR and DRIFT attachment. 1 H-NMR and T 1 measurements were carried out on a JEOL JNM-LA400 Spectrometer (400 MHz).Electronic absorption spectral titration experiments were done using a ThermoFisher Scientific Evolution 300 UV-Vis spectrophotometer.Electrospray ionisation mass spectrometry (ESI-MS) spectra of the compounds were recorded on Advion MS SOP electrospray ionisation (ESI) spectrometer.The pH measurements were done using a Jenway 3520 digital pH meter with a Mettler-Toledo 51343160 glass electrode.

Fig. S7 .
Fig. S7.The ATP-chelation of 1 mM of 2 by 25 mM molar excess equivalent of ATP was monitored by relaxivity change as a function of time.

Fig. S11 .
Fig. S11.T 1 -weighted MRI phantom images (1.5 T, 298 K) as a function of the concentration of MnCAs and different phosphates.

Fig. S9 .
Fig. S9.The chelating stability of 2 (MnL DPA-Zn ) was monitored by a change in the absorption spectral intensity over time in an aqueous solution (50 mM HEPES buffer) at pH 7.3, 298 K. Absorption spectra of 2 (50 μM) obtained over 8 days (A), Change in the absorption intensities at 217, 260, and 282 nm (B), and the ratio of Abs 282 /Abs 260 as the function of time (C).