Enzyme-Triggered Fe(CO)3 Complexes for Controlled CO Delivery

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current carbon monoxide-releasing molecules (CORMs) suffer from rapid and uncontrolled release of carbon monoxide, limiting their ability to deliver precise amounts to specific physiological targets, and lack enzymatic trigger mechanisms for targeted therapeutic applications.

Innovation Solution

Development of η4-1,3-diene-Fe(CO)3 complexes that enable enzymatically triggered release of carbon monoxide, with specific complexes designed to release CO upon hydrolysis by enzymes like esterases or lipases, providing controlled and targeted delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional carbon monoxide-releasing molecules (CORMs) are used, then carbon monoxide can be delivered to physiological targets, but the release is rapid and uncontrolled, limiting precise delivery

Engineering Contradiction:

Improveprecision of carbon monoxide deliveryVSAvoidcontrol over carbon monoxide release

Core Design Contradiction:

Measurement precisionVSStability of the object's composition

Solution Approach 1:

The patent applies dynamics by transitioning from static CORMs to enzyme-triggered dynamic release systems. The CORMs are designed to remain stable until encountering specific enzymes (esterases, lipases, phosphatases), at which point they dynamically release CO in a controlled manner. This dynamic trigger mechanism allows precise spatial and temporal control of CO delivery to physiological targets.

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent uses enzymes as intermediary triggers to control CO release. Instead of direct spontaneous release or external control, the system employs enzymatic intermediaries (esterases, lipases, phosphatases) that mediate the release process. This intermediary mechanism enables controlled CO delivery by leveraging the natural presence of these enzymes at specific physiological locations.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If gaseous carbon monoxide is used for delivery, then therapeutic effects can be achieved, but high affinity binding to hemoglobin causes systemic effects on oxygen transport and low bioavailability

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidsystemic effects on oxygen transport

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the CO from gaseous form and incorporates it into a stable iron carbonyl complex structure. This extraction transforms CO from a free gas that binds hemoglobin into a bound state within the CORM molecule, eliminating the harmful systemic effects while preserving therapeutic efficacy. The CO is only released at the target location where needed.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The iron carbonyl complex acts as an intermediary carrier that transports CO without causing hemoglobin binding issues. This intermediary complex form allows CO to be delivered to physiological targets while avoiding the harmful effects of gaseous CO, as the iron-CO bond prevents premature binding to hemoglobin.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Adaptability or versatility

If existing CORMs are used, then carbon monoxide can be released, but they lack enzymatic trigger mechanisms for targeted therapeutic applications

Engineering Contradiction:

Improvetargeted delivery capabilityVSAvoidenzymatic trigger mechanism

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies universality by designing CORMs that can be triggered by multiple enzyme types (esterases, lipases, phosphatases). This multi-functionality allows the same CORM structure to be activated by different enzymatic pathways present at various physiological targets, enhancing targeted delivery capability without requiring separate systems for each target type.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The CORMs are designed to be self-activating through enzymatic triggers that are naturally present at physiological targets. The system requires no external activation mechanism beyond the natural enzymatic environment, allowing the CORMs to automatically release CO where needed based on the presence of specific enzymes at the target location.

Inventive Principle:

Principle #25Self-service

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 η4-1,3-diene-Fe(CO)3 complexes achieve precise and controlled release of carbon monoxide, enhancing therapeutic efficacy by ensuring targeted delivery and reducing systemic side effects, thereby improving the treatment of various diseases and conditions.

Implementation Method 1

release of carbon monoxide can be enzymatically-triggered

Methodology Applied

Scientific EffectHydrolysis: Hydrolysis

Implementation Method 2

enzymes like esterases or lipases

Methodology Applied

Scientific EffectEnzymatic catalysis: Enzyme

Implementation Method 3

deliver carbon monoxide to a physiological target

Methodology Applied

Scientific EffectLigand dissociation: Chemical Bonding

Data Source

PatentUS8927750B2Acyloxy- and phosphoryloxy-butadiene-Fe(CO)<sub>3 </sub>complexes as enzyme-triggered co-releasing molecules

Publication Date: 2015.01.06 UNIVERSITY OF COLOGNE

AI summary

The present invention provides acyloxy- and phosphoryloxy-butadiene-Fe(CO)3 complexes which can deliver carbon monoxide to a physiological target, wherein release of carbon monoxide can be enzymatically-triggered. The present invention also provides for methods of manufacturing the enzymatically-triggered carbon monoxide releasing molecules and methods for their use.