ORIGINAL PAPER Benchmark DFT studies on C–CN homolytic cleavage and screening the substitution effect on bond dissociation energy Naveen Kosar 1 & Khurshid Ayub 1 & Mazhar Amjad Gilani 2 & Tariq Mahmood 1 Received: 22 September 2018 /Accepted: 9 January 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Nitriles are important chemical species in organic transformations, material chemistry, and environmental sciences. Nitriles are used as cyanating reagents in many organic reactions, where the C–CN bond dissociation has an important role. The reactivity of nitriles can be better understood by studying the bond dissociation energy (BDE) of the C–CN bond. In this benchmark study, homolytic cleavage of the C–CN bond in 12 nitrile compounds is studied. Thirty-one functionals from eight different DFT classes along with three types of basis sets are employed. Theoretical results are compared with the available experimental data. Based on statistical outcomes, the CAM-B3LYP functional of the range separated hybrid GGA class with Pople 6-311G(d,p) basis set provides the most accurate results for calculating the BDE of the C–CN bond. The mean absolute error (MAE) value is 0.06 kcal mol -1 , whereas standard deviation (SD) and Pearson’s correlation (R) are 2.79 kcal mol -1 and 0.96, respectively, when compared with experimental data. The substitutional effect on the homolytic cleavage (BDE) of respective bonds in differently substituted nitriles is also investigated. The BDE results indicate that electron withdrawing groups (EWGs) lower the BDE, while electron donating groups (EDGs) increase the BDE of the C–CN bond. The NBO and HOMO–LUMO orbitals analyses are also performed to further elaborate the variational BDE patterns of C–CN bond cleavage. Keywords Nitrile . DFT . Bond dissociation energy . Benchmark Introduction Nitrile is an important chemical entity that has an sp- hybridized nitrogen atom and wide spread applications in chemistry, biology, and environmental sciences [ 1–4]. Nitriles are important building blocks for various organic compounds, such as pyridine [5], indophenol [6], tetrazoles, optically active glutarimides [7], and C-nucleoside antibiotics (pyrazomycin, formycin, and showdomycin) [8]. In abiotic chemistry, nitriles have a vital role in the formation of biogen- ic amino acids and N-heterocycles, including purines (ade- nine, guanine) and pyrimidines (cytosine and uracil) [9]. Specially, acetonitrile acts as an excellent precursor for the synthesis of nitrile derived amino acids. Nitrile containing compounds are also beneficial as bridge linkers in transition metal complexes and in native vitamin B 12 [10]. Nitrile, as a substituent group, has a significant role in deciding the regioselectivity in many organic transformations [11]. Adrian and his coworkers examined the removal of the halogen group (for minimizing the environmental pollution) in 2-chloro-6-fluorobenzonitrile. They suggested that the elec- tron withdrawing nitrile group had assisted in the easy remov- al of the chloro group with high regioselectivity compared to the flouro group [12]. Nitriles in combination with rare gases, i.e., He, Ne, and Ar, are important species for the collision- induced electron energy transfer process in which production of a cyano-radical facilitates the resonance between the ground state and first two excited states [13]. Nitrile stretch is used as an important IR probe, antenna system, and electric field meter because of its small size and little perturbation of the protein environment under investigation [14]. Nitriles are Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00894-019-3930-x) contains supplementary material, which is available to authorized users. * Mazhar Amjad Gilani mazhargilani@cuilahore.edu.pk * Tariq Mahmood mahmood@cuiatd.edu.pk 1 Department of Chemistry, COMSATS University, Abbottabad Campus, Abbottabad 22060, Pakistan 2 Department of Chemistry, COMSATS University, Lahore Campus, Lahore, Pakistan Journal of Molecular Modeling (2019) 25:47 https://doi.org/10.1007/s00894-019-3930-x