Quantum Chemical Methods in Molecular Structure Determination

Quantum chemical methods have become indispensable tools for elucidating molecular geometries and electronic configurations with high precision. Density functional theory (DFT) offers a practical balance between computational efficiency and accuracy, enabling the optimisation of ground‐state structures and prediction of spectroscopic signatures. Wavefunction‐based approaches, such as complete active space self‐consistent field (CASSCF) and its perturbative extension (MCQDPT2), capture multiconfigurational character and dynamic correlation, proving essential for systems with near‐degenerate states or open‐shell electronic configurations. Time‐dependent DFT (TDDFT) further extends these capabilities to excited‐state properties, facilitating simulation of UV–Vis and other optical spectra. Advances in local correlation techniques, exemplified by domain‐based local pair natural orbital coupled‐cluster methods (DLPNO-CCSD), have pushed high‐accuracy treatments to larger molecular assemblies. These theoretical frameworks are routinely integrated with experimental probes—such as gas‐phase electron diffraction, X-ray absorption and vibrational spectroscopy—to resolve subtle conformational equilibria, non‐planar distortions and electronic rearrangements. Collectively, these quantum chemical strategies underpin progress in fields ranging from catalysis and materials design to drug discovery, enabling predictive modelling of reactivity, stability and spectral behaviour across diverse chemical landscapes.

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Quantum Chemical Methods in Molecular Structure Determination publication trend

The graph below shows the total number of articles in quantum chemical methods in molecular structure determination across all publications each year (not limited to Nature Index journals).

Technical terms

Density functional theory (DFT): A quantum mechanical method using electron density rather than wavefunction to compute ground‐state properties of molecules with a favourable cost–accuracy balance.

Complete active space self‐consistent field (CASSCF): A multiconfigurational wavefunction approach that variationally optimises orbitals and configuration interaction within a selected active space to capture static correlation.

Multiconfigurational quasi‐degenerate second‐order perturbation theory (MCQDPT2): A second‐order perturbative correction applied to CASSCF wavefunctions to recover dynamic correlation effects.

Time‐dependent density functional theory (TDDFT): An extension of DFT that models electronic excited states and simulates optical spectra by treating time‐dependent perturbations of electron density.

Gas‐phase electron diffraction (GED): An experimental technique for determining molecular geometries in the vapour phase by analysing electron scattering intensity patterns.

Domain‐based local pair natural orbital coupled‐cluster (DLPNO-CCSD): A highly efficient implementation of coupled‐cluster theory that exploits local correlations to enable accurate treatment of large molecules.

References

1. Gas-Phase Structure of 3,7,9-tris(trifluoromethylsulfonyl)-3,7,9-triazabicyclo[3.3.1]nonane by GED and Theoretical Calculations. Molecules (2023).
2. Comprehensive Study of Equilibrium Structure of Trans-Azobenzene: Gas Electron Diffraction and Quantum Chemical Calculations. Physchem (2024).
3. Molecular Structure of Nickel Octamethylporphyrin—Rare Experimental Evidence of a Ruffling Effect in Gas Phase. International Journal of Molecular Sciences (2021).