Two-dimensional electronic spectroscopy as a tool for tracking molecular conformations in DNA/RNA aggregates

Area of Science:

• Computational chemistry
• Spectroscopy
• Molecular dynamics

Background:

• Flexible molecular systems in solution present challenges for spectroscopic analysis.
• Understanding the relationship between molecular conformation and photochemical outcomes is crucial for DNA/RNA photostability.
• Existing methods may not fully capture the nuances of conformation-dependent spectral changes.

Purpose of the Study:

• To develop and apply a computational strategy for simulating two-dimensional electronic spectra (2DES) of flexible molecular systems.
• To analyze ground-state dynamics and sample various conformations of adenine-adenine monophosphate (ApA) in solution.
• To correlate specific molecular arrangements with distinct 2DES spectral fingerprints.

Main Methods:

• Employed an explicit mixed quantum mechanics/molecular mechanics (QM/MM) approach to calculate excited state energies and transition dipole moments.
• Utilized molecular dynamics simulations and cluster analysis to select representative conformations of the flexible ApA system.
• Applied a sum-over-states (SOS) approach to compute 2DES spectra for individual conformations.

Main Results:

• Distinct 2DES spectral features were identified for different adenine-adenine arrangements (π-stacked, T-stacked, unstacked).
• Close π-stacked bases showed splitting in their 1La signal traces.
• T-stacked bases displayed charge transfer states and no 1La splitting, while unstacked bases resembled adenine monomers.

Conclusions:

• 2DES spectral maps serve as unique fingerprints for specific molecular conformations.
• This computational strategy enables quantitative spectroscopic detection of molecular arrangements, surpassing standard 1D pump-probe techniques.
• The findings are expected to enhance understanding of how nucleobase aggregation impacts DNA/RNA photostability and photo-damage.