Enhanced Chelate Cooperativity in Polar Solvents

Area of Science:

• Supramolecular Chemistry
• Physical Organic Chemistry
• Spectroscopy

Background:

• Intramolecular hydrogen bonds play crucial roles in molecular recognition and stability.
• Polar solvents can compete with and disrupt intramolecular interactions, affecting binding affinities.
• Understanding solvent effects is key to designing molecules with predictable binding properties.

Purpose of the Study:

• To investigate the competitive effects of a polar solvent (phenol) on intramolecular hydrogen bond formation in zinc porphyrin-pyridine complexes.
• To quantify the impact of solvent composition on the effective molarity (EM) for intramolecular H-bond formation.
• To elucidate the interplay between solvent-solute interactions and cooperative binding effects.

Main Methods:

• High-throughput UV-vis titrations were employed to monitor complex formation.
• Chemical double-mutant cycles (DMCs) were utilized to determine effective molarities (EM).
• Studies were conducted on twenty-four zinc porphyrin-pyridine complexes in varying toluene-phenol solvent mixtures.

Main Results:

• Effective molarities (EM) for intramolecular phenol-amide H-bonds increased significantly (by an order of magnitude) with rising phenol concentration.
• Phenol strongly solvates amide groups, increasing steric bulk and destabilizing complexes.
• Formation of intramolecular H-bonds alleviates steric hindrance, enhancing the driving force for cooperative interactions.

Conclusions:

• Competitive solvation by polar solvents can be counteracted by increased effective molarity in multivalent systems.
• The study demonstrates a mechanism where solvent competition is attenuated by enhanced intramolecular H-bond formation.
• This work provides insights into the design of ligands and complexes with tunable binding affinities in the presence of competing solvents.