The solvent effects on the low-lying absorption spectrum and on the ¹⁵N chemical shielding of pyrimidine in water are calculated using the combined and sequential Monte Carlo simulation and quantum mechanical calculations. Special attention is devoted to the solute polarization. This is included by an iterative procedure previously developed where the solute is electrostatically equilibrated with the solvent. In addition, we verify the simple yet unexplored alternative of combining the polarizable continuum model (PCM) and the hybrid QM/MM method. We use PCM to obtain the average solute polarization and include this in the MM part of the sequential QM/MM methodology, PCM-MM/QM. These procedures are compared and further used in the discrete and the explicit solvent models. The use of the PCM polarization implemented in the MM part seems to generate a very good description of the average solute polarization leading to very good results for the n–π* excitation energy and the ¹⁵N nuclear chemical shield of pyrimidine in aqueous environment. The best results obtained here using the solute pyrimidine surrounded by 28 explicit water molecules embedded in the electrostatic field of the remaining 472 molecules give the statistically converged values for the low lying n–π* absorption transition in water of 36 900 ± 100 (PCM polarization) and 36 950 ± 100 cm⁻¹ (iterative polarization), in excellent agreement among one another and with the experimental value observed with a band maximum at 36 900 cm⁻¹. For the nuclear shielding ¹⁵N the corresponding gas–water chemical shift obtained using the solute pyrimidine surrounded by 9 explicit water molecules embedded in the electrostatic field of the remaining 491 molecules give the statistically converged values of 24.4 ± 0.8 and 28.5 ± 0.8 ppm, compared with the inferred experimental value of 19 ± 2 ppm. Considering the simplicity of the PCM over the iterative polarization this is an important aspect and the computational savings point to the possibility of dealing with larger solute molecules. This PCM-MM/QM approach reconciles the simplicity of the PCM model with the reliability of the combined QM/MM approaches.

A combination of the polarizable continuum model (PCM) and the hybrid quantum mechanics/molecular mechanics (QM/MM) methodology, PCM-MM/QM, is used to include the solute electronic polarization and then study the solvent effects on the low-lying n→π* excitation energy and the 15N nuclear magnetic shielding of pyrazine and pyridazine in aqueous environment. The results obtained with PCM-MM/QM are compared with two other procedures, i.e., the conventional PCM and the iterative and sequential QM/MM (I-QM/MM). The QM calculations are made using density functional theory in the three procedures. For the excitation energies, the time-dependent B3LYP/6-311+G(d) model is used. For the magnetic shielding, the B3LYP/aug-pcS2(N)/pcS2(C,O,H) is used with the gauge-including atomic orbitals. In both cases, i.e., PCM-MM/QM and I-QM/MM, that use a discrete model of the solvent, the solute is surrounded by a first shell of explicit water molecules embedded by an electrostatic field of point charges for the outer shells. The best results are obtained including 28 explicit water molecules for the spectral calculations and 9 explicit water molecules for the magnetic shielding. Using the PCM-MM/QM methodology the results for the n→π* excitation energies of pyridazine and pyrazine are 32 070 ± 80 cm−1 and 32 675 ± 60 cm−1, respectively, in good agreement with the corresponding I-MM/QM results of 32 540 ± 80 cm−1 and 32 710 ± 60 cm−1 and the experimental results of 33 450–33 580 cm−1 and 32 700–33 300 cm−1. For the 15N magnetic shielding, the corresponding numbers for the gas-water shifts obtained with PCM-MM/QM are 47.4 ± 1.3 ppm for pyridazine and 19.7 ± 1.1 ppm for pyrazine, compared with the I-QM/MM values of 53.4 ± 1.3 ppm and 19.5 ± 1.2 ppm and the experimental results of 42–54 ppm and 17–22 ppm, respectively. The agreement between the two procedures is found to be very good and both are in agreement with the experimental values. PCM-MM/QM approach gives a good solute polarization and could be considered in obtaining reliable results within the expected QM/MM accuracy. With this electronic polarization, the solvent effects on the electronic absorption spectra and the 15N magnetic shielding of the diazines in water are well described by using only an electrostatic approximation. Finally, it is remarked that the experimental and theoretical results suggest that the 15N nuclear magnetic shielding of any diazine has a clear dependence with the solvent polarity but not directly with the solute-solvent hydrogen bonds.