Alkynyl-Modified Ruthenium Complex for Enhanced Transmembrane Absorption
Solution Overview
Problem
Current anti-tumor drugs, including Ruthenium complexes, face challenges with poor selectivity and significant side effects on normal cells, limiting their efficacy and clinical application, while Ruthenium complexes with DPPZ as the main ligand have poor transmembrane absorption and limited anti-tumor activity due to their inability to enter tumor cells effectively.
Innovation Solution
Development of an alkynyl-modified Ruthenium (II) complex with DPPZ as the main ligand, synthesized using a method involving Sonogashira coupling to introduce an alkynyl group, enhancing transmembrane absorption and anti-tumor activity, and potentially reducing toxicity and side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Ruthenium complexes with DPPZ as the main ligand are used, then strong combining capacity with DNA is achieved, but transmembrane absorption is poor and anti-tumor activity is limited
Solution Approach 1:
The patent introduces an alkynyl group at a specific position of the DPPZ ligand structure. This local structural modification enhances the complex's ability to interact with cell membranes locally, improving transmembrane absorption without compromising the overall DNA binding capability of the DPPZ core structure.
Solution Approach 2:
The patent modifies the chemical structure parameters of the DPPZ ligand by introducing an alkynyl group with specific substituents (R = H, phenyl, or trimethylsilyl). These parameter changes in molecular structure alter the complex's physicochemical properties, enhancing membrane permeability while maintaining DNA binding affinity.
2Object-affected harmful factors
If alkyl chains and polypeptides are introduced to promote membrane permeability, then transmembrane absorption is improved, but molecular complexity increases
Solution Approach 1:
Instead of introducing complex polypeptide structures, the patent applies a relatively simple alkynyl group modification at a specific location on the DPPZ ligand. This local modification achieves improved membrane permeability without significantly increasing overall molecular complexity.
Solution Approach 2:
The patent uses controlled parameter changes in the ligand structure (introducing alkynyl groups with different R substituents) to optimize membrane permeability. This approach allows systematic tuning of the property without the complexity of polypeptide-based modifications.
3Adaptability or versatility
If anti-tumor drugs are used with broad-spectrum effects, then efficacy against multiple tumors is improved, but selectivity to cancer cells decreases and side effects increase
Solution Approach 1:
The patent introduces chiral centers through the alkynyl group modification, creating enantiomers with potentially different biological activities. This local structural feature enhancement may improve selectivity for cancer cells over normal cells, reducing side effects while maintaining broad-spectrum efficacy.
Solution Approach 2:
The patent creates composite structures by combining the Ruthenium complex core with modified DPPZ ligands containing alkynyl groups. This composite approach allows optimization of both anti-tumor activity and selectivity through the synergistic effects of the metal center and the modified organic ligand.
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 alkynyl-modified Ruthenium complex demonstrates improved transmembrane absorption and significant anti-tumor activity, particularly against breast cancer, offering new prospects for designing more effective anti-tumor drugs and serving as a fluorescence probe.
Implementation Method 1
the alkynyl-modified Ruthenium complex demonstrates improved transmembrane absorption and significant anti-tumor activity, particularly against breast cancer, offering new prospects for designing more effective anti-tumor drugs and serving as a fluorescence probe
Implementation Method 2
synthesized using a method involving Sonogashira coupling to introduce an alkynyl group
Data Source
AI summary
A Ruthenium complex containing alkynyl group, a method of synthesizing the Ruthenium complex containing alkynyl group and a use thereof are provided. The Ruthenium complex has a chemical formula of Ru(L)2(DPPZ′). DPPZ′ is a main ligand having structural formula ofR is any one selected from the group consisting of H, substituted or unsubstituted phenyl, R1NH2, R1OH, and SiMe3; R1 is C1-C5 chain alkyl group; L is an auxiliary ligand with N as coordinating atom. Sonogashira coupling reaction is utilized to introduce alkynyl group into a DPPZ-type Ruthenium complex; the introduced alkynyl group is beneficial to promote the transmembrane absorption of drug molecules, increase the probability of drug entry into cells, and can also increase efficacy and reduce toxic and side effects of drugs. The Ruthenium complex provided has significant anti-tumor activity, especially anti-breast cancer activity, and can provide new ideas for designing anti-tumor drug molecules in the future.