Pyridine, its N-oxide, and their derivatives are exciting classes of organic bases. These compounds show widespread biological activity, and they are often used in synthesis. In this work results on theoretical calculations of acid dissociation constants as pK a of pyridine, its N-oxide, and their derivatives were done based on the thermodynamic cycle in water and acetonitrile. Additionally, gas-phase basicity (GB) and proton affinity (PA) values were computed for systems studied. All pK a values were obtained using B3LYP, M06-2X, and G4MP2 methods in the gas phase, which were combined with the PCM model calculations (at the Hartree–Fock method) and with the use of four different scale factors alpha. Theoretical GB, PA, and pK a values were then compared with the available experimental ones. Results obtained from B3LYP and M06-2X methods are quite similar and compatible with experimental ones in terms of quality with correlation coefficients values R 2 higher than 0.9, whereas results received from G4MP2 deviate strongly. The calculated pK a values are highly sensitive to the scale factors alpha used in the computational procedure. Root-mean-square deviations (RMSD) between both theoretically and experimentally available pK a values of systems studied were also computed. The RMSD values are lower than 0.8 for the best results, suggesting that the theoretical model presented in this work is promising for applications for pK a calculations of different classes of compounds.

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Phosphorylated proteins take part in many signaling pathways and play a key role in homeostasis regulation. The all-atom force fields enable us to study the systems containing phosphorylated proteins, but they are limited to short time scales. In this paper, we report the extension of the physics-based coarse-grained UNRES force field to treat systems with phosphorylated amino-acid residues. To derive the respective potentials, appropriate physics-based analytical expressions were fitted to the potentials of mean force of systems modeling phosphorylated amino-acid residues computed in our previous work and implemented in UNRES. The extended UNRES performed well in ab initio simulations of two miniproteins containing phosphorylated residues, strongly suggesting that realistic large-scale simulations of processes involving phosphorylated proteins, especially signaling processes, are now possible.

Structure, ionic forms, hydrophilic and non-cytotoxic character of 2-hydrazinopyrazine with stronger affinity to BSA than DNA were proved.