Ruthenium Bisstyryl-Bipyridine Complexes for Deep-Tissue Photodynamic Therapy
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Solution Overview
Problem
Current photosensitizers used in photodynamic therapy, such as Photofrin, have limitations due to low solubility, aggregation, slow clearance, and hepatotoxicity, and Ru(II) polypyridine complexes lack significant absorption in the biological spectral window (600-900 nm), restricting their application in treating deep-seated tumors.
Innovation Solution
Development of metal complexes bearing (E-E′)-4,4′-bisstyryl-2,2′-bipyridine ligands that can be excited between 450-900 nm through one- or two-photon absorption, allowing for deeper tissue penetration and reduced tissue damage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Photofrin is used as photosensitizer, then it has been approved for treatment of various cancers, but it exhibits low solubility, aggregation, slow clearance, and hepatotoxicity
Solution Approach 1:
The patent modifies the chemical structure of photosensitizers by introducing Ru(II) polypyridine complexes with extended conjugation and specific ligand designs (LIG1, LIG2, LIG3 with various substituents R1-R17). These structural parameter changes improve aqueous solubility, reduce aggregation, and enhance metabolic clearance while maintaining photodynamic therapy efficacy through absorption in the 600-900 nm biological spectral window
Solution Approach 2:
The invention creates composite molecular structures combining ruthenium metal center with organic polypyridine ligands featuring extended π-conjugation (bisstyryl-bipyridine core). This composite approach integrates the benefits of metal coordination chemistry with organic chromophore properties to achieve improved solubility, reduced toxicity, and optimized photophysical characteristics for clinical application
2Reliability
If Ru(II) polypyridine complexes are used, then they possess attractive chemical and photophysical properties, but they lack significant absorption in the biological spectral window (600-900 nm)
Solution Approach 1:
The patent extends the π-conjugation of the polypyridine ligands by introducing bisstyryl-bipyridine cores with additional aromatic rings and conjugated double bonds. This increases the delocalization of electrons, red-shifting the absorption spectrum into the 600-900 nm biological spectral window while maintaining the photostability and chemical properties of Ru(II) complexes
Solution Approach 2:
The invention transitions from typical blue/UV-A absorbing complexes to those absorbing in the red/near-infrared region (600-900 nm). This dimensional shift in the electromagnetic spectrum enables deeper tissue penetration and treats deeper-seated tumors, as longer wavelengths are less energetic and cause less potential damage to surrounding healthy tissue
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
These metal complexes serve as effective photosensitizers for photodynamic therapy, enabling treatment of deep-seated tumors with improved tissue penetration and reduced toxicity, overcoming the limitations of existing photosensitizers.
Implementation Method 1
metal complexes bearing at least one (E-E′)-4,4′-bisstyryl-2,2′-bipyridine ligand which are able to be excited between 450-900 nm by either one- or two-photon absorption
Implementation Method 2
metal complexes bearing at least one (E-E′)-4,4′-bisstyryl-2,2′-bipyridine ligand which are able to be excited between 450-900 nm by either one- or two-photon absorption
Implementation Method 3
The effect of PDT relies on the combination of an ideally non-toxic molecule, so called photosensitizer (PS), oxygen and light
Data Source
AI summary
The present invention relates to metal complexes bearing at least one (E-E′)-4,4′-bisstyryl-2,2′-bipyridine ligand (LIG1) of the following formula (I): or a pharmaceutically acceptable salt and/or solvate thereof. The present invention also relates to pharmaceutical compositions comprising these complexes and at least one pharmaceutically acceptable excipient. The present invention also relates to the use of compounds of formula (I) or pharmaceutical compositions comprising thereof as drug and as photosensitizer agent in photodynamic therapy. The present invention relates to methods of preparation of said complexes.