A Study about Regioisomeric Hydroquinones with Multiple Intramolecular Hydrogen Bonding

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Organic Chemistry

Background:

• Antitumor tricyclic hydroquinones are a class of compounds with potential biological activity.
• Understanding intramolecular hydrogen bonding (IHB) is crucial for predicting and optimizing molecular interactions and biological activity.

Purpose of the Study:

• To theoretically investigate intramolecular hydrogen bonding in synthetic regioisomeric antitumor tricyclic hydroquinones.
• To correlate conformational energies with IHB strengths.
• To guide the design of novel biologically active molecules.

Main Methods:

• Theoretical exploration of four distinct IHB configurations.
• Conformational analysis of hydroxyalkyl substituent rotation.
• Evaluation of stabilization energies for IHB formation.
• Synthesis and structural assignment using 2D-NMR experiments.

Main Results:

• Identified four distinct intramolecular hydrogen bonding scenarios.
• Observed a correlation between conformational energies and IHB strength.
• Determined that six-membered ring IHBs (phenolic proton-carbonyl oxygen) are strongest.
• Found that five-membered ring IHBs (phenolic proton-chromenone oxygen) are weakest.
• Synthesized and characterized two pairs of regioisomeric hydroquinones.

Conclusions:

• The strength of intramolecular hydrogen bonds in these hydroquinones is dependent on the ring size formed.
• Stronger IHBs are associated with phenolic protons and carbonyl oxygens in six-membered rings.
• Weaker IHBs involve phenolic protons and chromenone oxygens in five-membered rings.
• These findings provide valuable insights for designing effective biologically active molecules.