Anionic Manganese(II) Chelates for MRI Contrast Agents
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Solution Overview
Problem
Current manganese(II) chelates for MRI contrast agents lack stability, which compromises their efficacy and safety profiles compared to gadolinium(III) chelates, despite manganese's potential for reduced toxicity.
Innovation Solution
Development of novel manganese(II) chelate compounds with a negative charge at physiological pH, designed to enhance stability and maintain strong magnetic resonance (MR) contrast, utilizing specific structural features and synthesis methods to improve chelation stability and clearance profiles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If manganese(II) chelates are used as MRI contrast agents, then toxicity is reduced compared to gadolinium(III) chelates, but chelate stability is significantly decreased
Solution Approach 1:
The patent changes the charge parameter of the chelate complex from neutral to negative by modifying the ligand structure. This parameter change fundamentally alters the stability characteristics of the manganese chelate, enabling it to achieve both reduced toxicity and improved stability simultaneously. The negative charge is achieved by incorporating additional carboxylate or phosphonate groups into the ligand framework.
Solution Approach 2:
The invention creates a composite chelate structure combining the manganese ion with a specifically designed polyaminocarboxylate or polyaminophosphonate ligand system. This composite structure integrates multiple functional groups (amine, carboxylate, phosphonate) that work synergistically to provide both stability and reduced toxicity, representing a composite material approach to solving the contradiction.
2Reliability
If conventional manganese(II) chelates are used, then they show potential for reduced toxicity, but they exhibit much lower stability compared to gadolinium(III) chelates
Solution Approach 1:
The patent applies parameter changes by modifying the ligand composition to include additional coordinating groups that increase the overall charge of the complex to negative. This changes the thermodynamic stability constants of the manganese chelate, bringing them into a range comparable to gadolinium chelates while maintaining the inherent safety advantages of manganese.
Solution Approach 2:
The patent introduces an intermediary ligand structure that acts as a mediator between the manganese ion and the biological environment. This ligand with negative charge serves as a protective intermediary that enhances stability while preventing direct interaction between free manganese ions and biological systems, thereby improving the safety profile.
3Stability of the object's composition
If neutral manganese chelates are used, then certain stability can be achieved, but clearance profile may be suboptimal
Solution Approach 1:
The patent changes the charge parameter from neutral to negative, which simultaneously affects both stability and clearance properties. The negative charge modifies the pharmacokinetic behavior of the chelate, improving renal clearance while maintaining stability through the enhanced chelation provided by the additional coordinating groups in the ligand structure.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The new manganese(II) chelates offer improved stability and safety profiles, potentially reducing toxicity risks while maintaining effective MR contrast, providing an alternative to gadolinium-based agents with altered clearance profiles.
Implementation Method 1
The manganese(II) ion is a paramagnetic species with a high spin number and a long electronic relaxation time and the potential of a Mn(II) based high relaxivity contrast agent has been reported in the literature
Implementation Method 2
Mn (II) has also been suggested as a less toxic alternative to Gd(III). However, known Mn(II) chelates have proved to be much less stable compared to corresponding Gd(III) chelates
Data Source
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AI summary
The invention provides compounds suitable for use as contrast agents in magnetic resonance imaging (MRI). The compounds of the present invention are manganese (II) complexes having advantageous properties as compared with similar known compounds.