A New 3D NICS Method Based on ESP Mapping

Introduction

Nucleus-Independent Chemical Shift (NICS) has become one of the most popular methods for assessing aromaticity, primarily due to its straightforward implementation. Despite its widespread use, evaluating the aromaticity of contorted molecules with NICS remains challenging. To address these difficulties, several three-dimensional approaches—such as 3D-ICSS and the 3D IMS map—have been proposed.

In this blog, I introduce a new 3D NICS approach that maps NICS values onto an electrostatic potential surface, thereby offering a more comprehensive understanding of the relationship between aromaticity and electron density (currently I name it as denNICS). A brief guide on how to implement denNICS is provided below. The source code required to perform these calculations is available here.

Method Overview

1. Compute Total Electron Density

Use Gaussian to calculate the total electron density. Make sure to save the results in a .fchk file.

2. Generate a .cube File

From the .fchk file, create a .cube file for the total electron density using the cubegen module or GaussView.

3. Run the Script (First Pass)

• Execute the script and provide the path to the .cube file when prompted.
• Press Enter. The script will generate multiple .gjf files and a .pm file.

  Note: You can modify the computational method in the script at lines 77 and 79 to suit your needs.

4. Submit the .gjf Files

Run all generated .gjf files in Gaussian.

5. Run the Script (Second Pass)

• Once the Gaussian calculations are complete, rerun the script.
• Provide the path to any of the resulting .log files when prompted and press Enter.
• A new .cube file named denNICS.cube will be generated.

6. Map denNICS.cube

Finally, visualize denNICS.cube alongside the total electron density. This combined mapping allows for a clearer, more detailed picture of how aromaticity correlates with the underlying electron density distribution.

Following is an example for a phenanthrene trimer (ref.: 10.1039/d1sc03368a).

This procedure offers a practical way to investigate the aromaticity of complex molecules by integrating NICS values onto an electrostatic potential surface. By following the steps outlined, researchers can gain deeper insight into the interplay between aromaticity and electron density in three-dimensional space.

Currently, denNICS is still in development, and I plan to integrate it into the next version of py.Aroma. In the meantime, if you encounter any issues with this method, please don’t hesitate to reach out.