Cyclam Bis-Phosphorus Ligands for Copper Complexation
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Solution Overview
Problem
Current ligands for copper radioisotopes have slow complexation rates and unsuitable redox potentials, making them inefficient for diagnostic and therapeutic applications, particularly in PET and SPECT imaging, due to non-selective biodistribution and low specific activity.
Innovation Solution
Development of cyclam-based compounds with bis-phosphorus acid groups that form thermodynamically stable and kinetically inert complexes with Cu2+ ions, enabling rapid and selective complexation and conjugation with targeting vectors for targeted biodistribution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If current ligands are used for copper radioisotopes, then complexation can occur, but the complexation rates are slow and specific activity is low
Solution Approach 1:
The patent modifies the ligand structure by incorporating bis-phosphorus acid groups into the cyclam framework, changing the chemical parameters of the ligand to achieve faster complexation kinetics and higher thermodynamic stability with copper radioisotopes, thereby resolving the contradiction between complexation rate and specific activity
Solution Approach 2:
The invention creates a composite ligand system combining cyclam macrocycle with bis-phosphorus acid moieties, leveraging the synergistic effects of both structural elements to achieve enhanced complexation properties that neither component could provide alone, thus improving both productivity and reliability
2Reliability
If current ligands are used, then copper complexation occurs, but biodistribution is non-selective
Solution Approach 1:
The patent introduces targeting moieties at specific locations on the ligand molecule (local modification) while maintaining the core cyclam-bisphosphorus structure, enabling selective biodistribution to target tissues without sacrificing the fundamental copper complexation capability, thus resolving the contradiction between specificity and versatility
3Stability of the object's composition
If thermodynamically stable complexes are formed, then complex stability increases, but complexation kinetics may slow down
Solution Approach 1:
The patent designs the ligand to exhibit dynamic behavior during complexation, where the flexible cyclam macrocycle can adapt its conformation to facilitate rapid metal binding, then transitions to a rigid, stable complex structure afterward, thereby achieving both fast kinetics and high thermodynamic stability
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 cyclam-based compounds with bis-phosphorus acid groups achieve high specific activity, allowing for rapid and selective complexation of Cu2+ ions, enhancing their suitability for diagnostic and therapeutic applications by improving complexation rates and biodistribution specificity.
Implementation Method 1
cyclam based compounds with coordinating side chains form thermodynamically very stable complexes with a wide scale of metal ions
Data Source
AI summary
Cyclam based compounds, their conjugates, co-ordination compounds, pharmaceutical composition containing thereof, method of preparation and use thereof The present invention relates to cyclam based compounds of the general formula (I), conjugates of such compounds with conjugation groups, their coordination compounds, targeting conjugates, method of preparation of cyclam based compounds, intermediate products for the preparation of cyclam based compounds, a pharmaceutical preparation containing them, and the use thereof.