Computational Analysis of HNPCA Compound

The compound HNPCA was fully optimized in the gas phase using the DFT method. The functional used was B3LYP [41 (link), 42 (link)] with the 6–311 +  + G(d,p) basis set. HNPCA was also optimized in methanol using the same theoretical method within the PCM solvation model [43 , 44 (link)] The ground-state structure was confirmed by frequency computations with the absence of imaginary frequency in both the gas phase and methanol. The optimized structure of HNPCA in methanol was used for computing chemical shifts with the Gauge-Including Atomic Orbital method [45 (link)] using isotropic shieldings of tetramethylsilane (TMS) computed using the same method. The non-covalent interaction (NCI), based on the reports of Johnson et al. [46 (link)], was explored by the noncovalent interaction-reduced density gradient (NCI-RDG) analysis using the Multiwfn program [47 (link)]. The isosurfaces were plotted using the Visual Molecular Dynamic (VMD) software [48 (link)] and The Gnuplot 4.2 program [49 ] and Ghostscript interpreter were employed to generate the 2D plots. All computations were carried out at 1 atm and 298.15 K using Gaussian 16 [50 ]. Visualization of the output files was done using GaussView 6 [51 ] and Chemcraft [52 ]. The coordinates of the optimized structure of HNPCA in the gas phase and methanol are provided in Table S1 of the supplementary information.
The interactions in the crystal structure of HNPCA were investigated by the Hirshfeld surface analysis [53 (link)] along with their 2D fingerprint plots [54 (link)] which were generated using the CrystalExplorer17.5 software [55 ]. Hirshfeld surface is represented by d_e and d_i, denoting the distance from the nearest atom outside and inside of the surface, respectively, and both are used to define the normalized contact distance (d_norm) with respect to the Van der Waals (vdW) radii as per Eq. 1. $$d_{\mathit{norm}}=\frac{(d_i-r_i^{\mathit{vdW}})}{r_i^{\mathit{vdW}}}+\frac{(d_e-r_e^{\mathit{vdW}})}{r_e^{\mathit{vdW}}}$$
For the visualization of d_norm, a red-blue-white color scale was selected. The red color denotes a negative value of the d_norm whereas the blue color denotes a positive value of the d_norm. The positive and negative values of the d_norm denote whether intermolecular interactions are larger or smaller than the vdW separation respectively. Therefore, the mapping of d_norm on the Hirshfeld surface illustrates the donor and acceptor properties and helps in the analysis of the intermolecular interactions.