Recent Developments of Computational Methods for pKa Prediction Based on Electronic Structure Theory with Solvation Models

The protonation/deprotonation reaction is one of the most fundamental processes in solutions and biological systems. Compounds with dissociative functional groups change their charge states by protonation/deprotonation. This change not only significantly alters the physical properties of a compound itself, but also has a profound effect on the surrounding molecules. In this paper, we review our recent developments of the methods for predicting the Ka, the equilibrium constant for protonation reactions or acid dissociation reactions. The pKa, which is a logarithm of Ka, is proportional to the reaction Gibbs energy of the protonation reaction, and the reaction free energy can be determined by electronic structure calculations with solvation models. The charge of the compound changes before and after protonation; therefore, the solvent effect plays an important role in determining the reaction Gibbs energy. Here, we review two solvation models: the continuum model, and the integral equation theory of molecular liquids. Furthermore, the reaction Gibbs energy calculations for the protonation reactions require special attention to the handling of dissociated protons. An efficient method for handling the free energy of dissociated protons will also be reviewed.

Quantum Chemical Analysis of the Corrosion Inhibition Potential by Aliphatic Amines

Destructive corrosion processes lead to the loss of primary mechanical properties of metal construction materials, which generates additional costs during their maintenance connected with repairs and protection. The effectiveness of corrosion inhibitors can be determined by using many methods, in particular quantum chemical modeling. The subject of the theoretical analyses presented in this work involves the anticorrosion properties of amines with various chemical structures. Evaluation of the corrosion inhibition properties of selected amines was performed on the basis of the HOMO–LUMO energy gap, dipole moment (µ), electronegativity (χ) determined as a result of the energy of the highest occupied molecular orbital (HOMO) and the energy of the lowest unoccupied molecular orbital (LUMO). Moreover, the HSAB (Hard and Soft Acids and Bases) theory was used to explain the reactivity of the analyzed amines, while the Mulliken population analysis was used to determine their electrostatic interactions with the surface of protected metal. The obtained results indicate that the protonation reaction of aliphatic amines leads to a change in the nature of the formation of a coordination bond with the surface of the protected metal. In turn, the quantum chemical calculations showed that the protonation reaction of aliphatic amines leads to a decrease in their corrosion inhibition efficiency. Most of the analyzed parameters indicated that tertiary amines are characterized by the highest corrosion inhibition efficiency.

Characterization of a polyaniline/pre-oxidized fiber felt electromagnetic wave absorbing composite

Firstly, a polyaniline/pre-oxidized fiber felt composite was prepared by in situ polymerization using pre-oxidized fiber felt as the substrate, aniline as the monomer, ammonium persulfate as the oxidant, and p-toluenesulfonic acid as the dopant. Secondly, the electromagnetic wave absorbing property and tensile property of the polyaniline/pre-oxidized fiber felt composite were investigated. Finally, the structure and composition were characterized by Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, and differential scanning calorimetry. The results show that the reflection loss of the polyaniline/pre-oxidized fiber felt composite is the smallest at the 3000 MHz frequency, reaching –8.23 dB, and the average surface resistance is 2059.84 Ω, with good conductivity. The characterization analysis shows that polyaniline has been successfully loaded on the pre-oxidized fiber felt, and the protonation reaction occurs at the nitrogen atom on the imine -N-. The polyaniline structure is doped by p-toluenesulfonic acid with a certain degree of order and crystallinity, and the composite has good thermal stability.

Axial-Ligand-Cleavable Silicon Phthalocyanines Triggered by Near-Infrared Light toward Design of Photosensitizers for Photoimmunotherapy

Near-infrared photoimmunotherapy (NIR-PIT) is a novel phototherapy for the treatment of cancer that uses NIR light and conjugates of antibody-IR700, a silicon phthalocyanine photosensitizer. A key feature of NIR-PIT is light-induced axial ligand cleavage of IR700, which finally causes cytotoxicity. Here, we focused on protonation of the axial ligand on the IR700 anion radical during the photochemical process. The Gibbs energy in the protonation reaction of IR700 derivatives with different axial ligands was calculated. These calculations suggested the order of the cleavage efficiency corresponds to the basicity of the axial ligand (i.e. alkoxy > siloxy (IR700) > phenoxy ≈ oxycarbonyl), which was confirmed by the photoirradiation experiments with synthesized compounds. Thus, axial ligand cleavage is significantly dependent on the basicity of the axial ligand. Our findings suggest that PIT reagent with an IR700 derivative bearing alkoxy group would show better efficacy than IR700.

Examining the Modular Synthesis of [Cp*Rh] Monohydrides Supported by Chelating Diphosphine Ligands

[Cp*Rh] hydride complexes are invoked as intermediates in certain catalytic cycles, but few of these species have been successfully prepared and isolated, contributing to a relative shortage of information on the properties of such species. Here, the synthesis, isolation, and characterization of two new [Cp*Rh] hydrides are reported; the hydrides are supported by the chelating diphosphine ligands bis(diphenylphosphino)methane (dppm) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos). In both systems, reduction of precursor Rh(III) chloride complexes with Na(Hg) results in clean formation of isolable, formally 18e– Rh(I) species, and subsequent protonation by addition of near-stoichiometric quantities of anilinium triflate to the Rh(I) species returns high yields of the desired monohydride complexes. Single-crystal X-ray diffraction data for these compounds provide evidence of direct Rh–H interactions, confirmed by complementary infrared spectra showing Rh–H stretching frequencies at 1982 cm–1 (for the dppm-supported hydride) and 1936 cm–1 (for the Xantphos-supported hydride). Findings from comprehensive multinuclear NMR experiments reveal the properties of the unique and especially rich spin systems for the dppm-supported hydride; multifrequency NMR studies in concert with spectral simulations enabled full characterization of splitting patterns attributable to couplings involving diastereotopic methylene protons for this complex. Taken together with prior reports of related monohydrides, the results show that the reduction/protonation reaction sequence is modular for preparation of [Cp*Rh] monohydrides supported by diverse diphosphine ligands spanning from four- to eight-membered rhodacycles.

Synergistic Catalysis of Tandem Michael Addition/Enantioselective Protonation Reactions by an Artificial Enzyme

Enantioselective protonation is conceptually one of the most attractive methods to generate an α-chiral center. However, enantioselective protonation presents major challenges, especially in water as a solvent. Herein, we report an artificial enzyme catalyzed tandem Michael addition and enantioselective protonation reaction of α-substituted acroleins with 2-acyl imidazole derivatives in water. The artificial enzyme uses a synergistic combination of two abiological catalytic sites: a genetically encoded non-canonical p-aminophenylalanine residue and a Lewis acid Cu(II) complex. The exquisite stereochemical control achieved in the protonation of the transient enamine intermediate generated by conjugate addition of the Michael donor is illustrated by the >20:1 dr and up to >99% ee obtained for the products. These results illustrate the potential of exploiting synergistic catalysis in artificial enzymes for challenging reactions.<br>

Synergistic Catalysis of Tandem Michael Addition/Enantioselective Protonation Reactions by an Artificial Enzyme

Enantioselective protonation is conceptually one of the most attractive methods to generate an α-chiral center. However, enantioselective protonation presents major challenges, especially in water as a solvent. Herein, we report an artificial enzyme catalyzed tandem Michael addition and enantioselective protonation reaction of α-substituted acroleins with 2-acyl imidazole derivatives in water. The artificial enzyme uses a synergistic combination of two abiological catalytic sites: a genetically encoded non-canonical p-aminophenylalanine residue and a Lewis acid Cu(II) complex. The exquisite stereochemical control achieved in the protonation of the transient enamine intermediate generated by conjugate addition of the Michael donor is illustrated by the >20:1 dr and up to >99% ee obtained for the products. These results illustrate the potential of exploiting synergistic catalysis in artificial enzymes for challenging reactions.<br>

Unexpected Catalytic Activity of the Regulatory Protein QacR

Natural proteins often present binding or functional promiscuity. In biocatalysis, this promiscuity has been exploited for accessing new-to-nature reactions. Here, we report an unexpected catalytic reactivity for the regulatory protein QacR from the TetR family of multidrug resistance regulators. QacR is able to catalyze the enatioselective tandem Friedel-Crafts / enantioselective protonation reaction of indoles with alpha substituted conjugated enones with up to 40% yield and 83% ee. Mutagenesis and computational studies support the hypothesis that an acidic residue in the binding pocket of the protein is responsible for protonating the enolate intermediate.

Unexpected Catalytic Activity of the Regulatory Protein QacR

Natural proteins often present binding or functional promiscuity. In biocatalysis, this promiscuity has been exploited for accessing new-to-nature reactions. Here, we report an unexpected catalytic reactivity for the regulatory protein QacR from the TetR family of multidrug resistance regulators. QacR is able to catalyze the enatioselective tandem Friedel-Crafts / enantioselective protonation reaction of indoles with alpha substituted conjugated enones with up to 40% yield and 83% ee. Mutagenesis and computational studies support the hypothesis that an acidic residue in the binding pocket of the protein is responsible for protonating the enolate intermediate.

Investigation of Carbohydrate C-Silylation with Chlorosilanes

We studied possibility of silylation of lithiated carbohydrates using chlorosilanes. We observed that after the lithiation, the silylation is concurrent with a protonation reaction. In the case of trimethyl chlorosilane, we achieved 1:1 ratio with 36% isolated yield, while triphenyl chlorosilane gave 1:2 (silylated:reduced) ratio and 4% isolated yield. In the case of benzyl protected carbohydrate, silylation at benzylic position was observed.