Kinetic control concept for the diffusion processes of paracetamol active molecules across affinity polymer membranes from acidic solutions

Background Paracetamol compound remains the most used pharmaceutical as an analgesic and antipyretic for pain and fever, often identified in aquatic environments. The elimination of this compound from wastewater is one of the critical operations carried out by advanced industries. Our work objective was to assess studies based on membrane processes by using two membranes, polymer inclusion membrane and grafted polymer membrane containing gluconic acid as an extractive agent for extracting and recovering paracetamol compound from aqueous solutions. Result The elaborated membrane characterizations were assessed using Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Kinetic and thermodynamic models have been applied to determine the values of macroscopic (P and J0), microscopic (D* and Kass), activation and thermodynamic parameters (Ea, ΔH#, ΔS#, ΔH#diss, and ΔH#th). All results showed that the PVA–GA was more performant than its counterpart GPM–GA, with apparent diffusion coefficient values (107D*) of 41.807 and 31.211 cm2 s−1 respectively, at T = 308 K. In addition, the extraction process for these membranes was more efficient at pH = 1. The relatively low values of activation energy (Ea), activation association enthalpy (ΔH≠ass), and activation dissociation enthalpy (ΔH≠diss) have indicated a kinetic control for the oriented processes studied across the adopted membranes much more than the energetic counterpart. Conclusion The results presented for the quantification of oriented membrane process ensured clean, sustainable, and environmentally friendly methods for the extraction and recovery of paracetamol molecule as a high-value substance.

Machine learning enabling prediction of the bond dissociation enthalpy of hypervalent iodine from SMILES

Machine learning to create models on the basis of big data enables predictions from new input data. Many tasks formerly performed by humans can now be achieved by machine learning algorithms in various fields, including scientific areas. Hypervalent iodine compounds (HVIs) have long been applied as useful reactive molecules. The bond dissociation enthalpy (BDE) value is an important indicator of reactivity and stability. Experimentally measuring the BDE value of HVIs is difficult, however, and the value has been estimated by quantum calculations, especially density functional theory (DFT) calculations. Although DFT calculations can access the BDE value with high accuracy, the process is highly time-consuming. Thus, we aimed to reduce the time for predicting the BDE by applying machine learning. We calculated the BDE of more than 1000 HVIs using DFT calculations, and performed machine learning. Converting SMILES strings to Avalon fingerprints and learning using a traditional Elastic Net made it possible to predict the BDE value with high accuracy. Furthermore, an applicability domain search revealed that the learning model could accurately predict the BDE even for uncovered inputs that were not completely included in the training data.

Current view on the assessment of antioxidant and antiradical activities: A mini review

The main problems in assessing the antioxidant properties of plant biologically active compounds are discussed in this review. Antioxidant potential should be considered as a combination of antioxidant and antiradical activities, since antiradical activity is part of the antioxidant activity and does not always coincide with antioxidant activity. The mechanisms of action and the existing experimental and computational methods for their evaluation were reviewed. Methods like FRAP, CUPRAC etc. could be used for assessment of antioxidant activity of plant compounds, but it is necessary to perform studies on cell cultures or laboratory animals in order to determine mechanisms of action on the antioxidant system of a living organism. The current methodological approaches for studying antiradical activity and its mechanisms include experimental methods such as DPPH, ABTS and ORAC, and computational methods based on density functional theory. The main thermodynamic parameters for evaluating antiradical mechanisms (HAT, SET-PT and SPLET) are the bond dissociation enthalpy, ionization potential, proton dissociation enthalpy, proton affinity, and electron transfer enthalpy, among others. The existing approaches for determining the antiradical mechanisms of antioxidants are quite informative, but can still cannot predict or determine by in vitro methods the antioxidant mechanism of these compounds in organisms consisting of many complex individual systems.

A Deep Insight in the Antioxidant Property of Carnosic Acid: From Computational Study to Experimental Analysis

Since the deep cause for the anti-oxidation of carnosic acid (CA) against oleic acid (OA) remains unclear, we focused on exploring the CA inhibition mechanism via a combined experimental and computational study. Atomic charge, total molecular energy, phenolic hydroxyl bond dissociation enthalpy (BDE), the highest occupied molecular orbital (HOMO), and the lowest unoccupied orbital (LUMO) energy were first discussed by the B3LYP/6-31G (d,p) level, a density functional method. A one-step hydrogen atom transfer (HAT) was proposed for the anti-oxidation of CA towards OA, and the Rancimat method was carried out for analyzing the thermal oxidation stability. The results indicate that the two phenolic hydroxyl groups located at C7(O15) and C8(O18) of CA exert the highest activity, and the chemical reaction heat is minimal when HAT occurs. Consequently, the activity of C7(O15) (303.27 kJ/mol) is slightly lower than that of C8(O18) (295.63 kJ/mol), while the dissociation enthalpy of phenol hydroxyl groups is much lower than those of α-CH2 bond of OA (C8, 353.92 kJ/mol; C11, 353.72 kJ/mol). Rancimat method and non-isothermal differential scanning calorimetry (DSC) demonstrate that CA outcompetes tertiary butylhydroquinone (TBHQ), a synthetic food grade antioxidant, both in prolonging the oxidation induction period and reducing the reaction rate of OA. The Ea (apparent activation energies of reaction) of OA, TBHQ + OA, and CA + OA were 50.59, 57.32 and 66.29 kJ/mol, revealing that CA could improve the Ea and thermal oxidation stability of OA.

First and Second Dissociation Enthalpies in Bi-Component Crystals Consisting of Maleic Acid and L-Phenylalanine

The energetics of the stepwise dissociation of a A:B2 bi-component crystal, according to A:B2(cr) → A:B(cr) + B(cr) and A:B(cr) → A(cr) + B(cr), was investigated using MA:Phe2 and MA:Phe (MA = maleic acid; Phe = L-phenylalanine) as model systems. The enthalpy changes associated with these sequential processes and with the overall dissociation reaction A:B2(cr) → A(cr) + 2B(cr) were determined by solution calorimetry. It was found that they are all positive, indicating that there is a lattice enthalpy gain when MA:Phe2 is formed, either from the individual precursors or by adding Phe to MA:Phe. Single-crystal X-ray diffraction (SCXRD) analysis showed that MA:Phe2 is best described as a protic salt containing a maleate anion (MA−) and two non-equivalent L-phenylalanine units, both linked to MA− by NH···O hydrogen bonds (H-bond): one of these units is protonated (HPhe+) and the other zwitterionic (Phe±). Only MA− and HPhe+ molecules are present in the MA:Phe lattice. In this case, however, NH···O and OH···O H-bonds are formed between each MA− unit and two HPhe+ molecules. Despite these structural differences, the enthalpy cost for the removal of the zwitterionic Phe± unit from the MA:Phe2 lattice to yield MA:Phe is only 0.9 ± 0.4 kJ mol−1 higher than that for the dissociation of MA:Phe, which requires a proton transfer from HPhe+ to MA− and the rearrangement of L-phenylalanine to the zwitterionic, Phe±, form. Finally, a comparison of the dissociation energetics and structures of MA:Phe and of the previously reported glycine maleate (MA:Gly) analogue indicated that parameters, such as the packing coefficient, density, hydrogen bonds formed, or fusion temperature, are not necessarily good descriptors of dissociation enthalpy or lattice enthalpy trends when bi-component crystals with different molecular composition are being compared, even if the stoichiometry is the same.

Theoretical Study of 2-(Trifluoromethyl)phenothiazine Derivatives with Two Hydroxyl Groups in the Side Chain-DFT and QTAIM Computations

Phenothiazines are known as synthetic antipsychotic drugs that exhibit a wide range of biological effects. Their properties result from the structure and variability of substituents in the heterocyclic system. It is known that different quantum chemical properties have a significant impact on drug behavior in the biological systems. Thus, due to the diversity in the chemical structure of phenothiazines as well as other drugs containing heterocyclic systems, quantum chemical calculations provide valuable methods in predicting their activity. In our study, DFT computations were applied to show some thermochemical parameters (bond dissociation enthalpy—BDE, ionization potential—IP, proton dissociation enthalpy—PDE, proton affinity—PA, and electrontransfer enthalpy—ETE) describing the process of releasing the hydrogen/proton from the hydroxyl group in the side chain of four 2-(trifluoromethyl)phenothiazine (TFMP) derivatives and fluphenazine (FLU). Additional theoretical analysis was carried out based on QTAIM theory. The results allowed theoretical determination of the ability of compounds to scavenge free radicals. In addition, the intramolecular hydrogen bond (H-bond) between the H-atom of the hydroxyl group and the N-atom located in the side chain of the investigated compounds has been identified and characterized.

DFT Study of Structure and Radical Scavenging Activity of Natural Pigment Delphinidin and Derivatives

A theoretical evaluation of the antioxidant activity of natural pigment delphinidin (1a) and derivatives 1b, 1c, 1d & 1e was performed using the DFT-B3LYP/6–311 + G (d, p) level of theory. Three potential working mechanisms, hydrogen atom transfer (HAT), stepwise electron transfer proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET), have been investigated. The physiochemical parameters, including O–H bond dissociation enthalpy (BDE), ionization potential (IP), proton dissociation enthalpy (PDE), proton affinity (PA), and electron transfer enthalpy (ETE), have been calculated in the gas phase and aqueous phase. The study found that the most suitable mechanism for explaining antioxidant activity is HAT in the gas phase and SPLET in the aqueous medium in this level of theory. Spin density calculation and delocalization index of studied molecules also support the radical scavenging activity. When incorporated into natural pigment delphinidin, the gallate moiety can enhance the activity and stability of the compounds.

Structure-antioxidant Activity (Oxygen Radical Absorbance Capacity) Relationships of Phenolic Compounds

Antioxidant capacity is the extent to which a compound can eliminate reactive oxygen species, and in vitro methods for its chemical evaluation have been proposed. Among these methods, the oxygen radical absorbance capacity (ORAC) assay comes close to the oxidation reaction in the living body because it generates radical species that mimic the lipid peroxyl radical involved in the peroxidation reaction of biological components and react in a phosphate buffer. In this study, PM7, a semi-empirical molecular orbital method, was used to calculate the thermodynamic properties (bond dissociation enthalpy, ionisation potential, and proton affinity) associated with ORAC. We also applied the clusterwise linear regression analysis as a statistical method for grouping the antioxidants by structure. By analysing the data for antioxidants, the trend in the hydrophilic ORAC values was determined using the calculated structures and bond dissociation enthalpies of the groups classified according to the presence or absence of oxygen functional groups in the ortho position of phenol. Further studies of indicators other than bond dissociation enthalpy are needed to predict the ORAC of other antioxidants such as flavonoids and indoles.