Bisphosphonate MOFs for Stable Nitric Oxide Release in Biofluids
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Solution Overview
Problem
Existing metal-organic frameworks (MOFs) face challenges in achieving high stability and controlled release of Lewis-based gases like NO in biological media, with issues such as rapid degradation and non-targeted release of toxic side products, limiting their use in therapeutic applications.
Innovation Solution
Development of ultra-microporous crystalline metal organic frameworks (MOFs) with bisphosphonic acid ligands, such as MIP-210(M), which are synthesized under mild conditions and exhibit high stability and selective adsorption of Lewis-based gases, allowing for prolonged release in biological media.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If iron(III) based MOFs are used for biomedical applications, then low toxicity and biocompatibility are achieved, but chemical stability in body fluids deteriorates
Solution Approach 1:
The patent employs composite materials by combining iron(III) metal nodes with carboxylate ligands to form MOF structures that integrate the low toxicity of iron with the enhanced stability of the framework architecture, enabling biocompatible yet stable gas delivery systems in physiological conditions
Solution Approach 2:
The patent applies parameter changes by modifying the MOF structure through coordination unsaturated sites (CUS) and specific pore engineering, which alter the interaction strength with NO gas and control release kinetics, thereby achieving stable yet controllable gas delivery in biological media
2Productivity
If MOFs are used for controlled release of nitric oxide, then gas delivery capability is improved, but release duration is insufficient for extended period applications
Solution Approach 1:
The patent applies dynamics by designing MOFs with coordination unsaturated sites that enable dynamic control of NO release - the CUS allow the MOF to respond to physiological conditions and release gas over extended periods through controlled coordination and decoordination processes, achieving sustained delivery beyond conventional MOF limitations
Solution Approach 2:
The patent utilizes porous materials by engineering MOF structures with specific pore sizes, shapes, and surface areas that enhance gas loading capacity and control release kinetics, allowing extended duration delivery through the porous framework's ability to store and gradually release NO over time
3Ease of manufacture
If polycarboxylate linkers are used in iron MOFs, then ease of synthesis is improved, but chemical stability in body fluids deteriorates
Solution Approach 1:
The patent applies parameter changes by systematically varying ligand structures, metal-to-ligand ratios, and synthesis conditions to optimize both the ease of fabrication and the chemical stability of iron MOFs, achieving materials that are both manufacturable and stable in physiological environments
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 MOFs provide an unprecedented controlled release of NO for over 72 hours in biological fluids, ensuring stability and biocompatibility, making them suitable for therapeutic applications like wound healing and anticancer treatment.
Implementation Method 1
NO is a gasotransmitter that exerts a host of signaling effects on several biological targets... NO is known to bind strongly Lewis acid sites from certain types of MOFs (e.g. MIL-100 (Fe)) prior to be released when in contact with water
Implementation Method 2
NO is known to bind strongly Lewis acid sites from certain types of MOFs
Implementation Method 3
Metal-organic frameworks (MOFs) are a versatile class of porous hybrid crystalline architectures, developed in the last decades, made from the association of inorganic moieties and polycomplexing organic linkers
Implementation Method 4
NO is known to bind strongly Lewis acid sites from certain types of MOFs (e.g. MIL-100 (Fe)) prior to be released when in contact with water
Data Source
AI summary
The present invention belongs to the field of nanoporous materials, in particular metal organic frameworks (MOFs) and Lewis-based gas delivery and/or slow release, or the detection of Lewis-based gas(es) in gases or liquid streams.The present invention relates, inter alia, to a new ultra-microporous crystalline metal organic framework solid (comprising bisphosphonic acid ligands (also referred to as Phosphonate MOF), such as MIP-210(M) and uses thereof as a carrier in Lewis-based gas (such as NO) delivery. The invention also relates to controlled release of the Lewis-based gas in wounds, for example by topical application. The invention also encompasses a synthetic method for producing the new ultra-microporous crystalline metal organic framework solid of the invention.The MOFs of the present invention can be used in various applications such as gas carrier and/or for the controlled release of gas. The MOFs of the present invention thus are very versatile and have therapeutic and non therapeutic applications.