Steric Energy Research Articles

A real space picture of the role of steric effects in SN 2 reactions.

Within substitution reactions, the Bimolecular Nucleophilic Substitution (SN2) reaction mechanism is one of the most frequently found and studied ones. Among other factors, the easiness of the SN2 pathway is classically considered to be determined by steric hindrance. However, the diffuse nature of the latter inevitably darkens these and other arguments holding the pillars of chemical intuition. In this work, we employ the steric energy (E ST ) descriptor, formulated within the Interacting Quantum Atoms approach, to offer insights regarding this problem. The steric demands of the substrate, nucleophile and leaving group were studied using the gas‐phase SN2 reaction with different organic skeletons (CH3—, CH3CH2—, (CH3)2CH—, (CH3)3C—, (CH3)3CCH2—) and halogens (F, Cl, and Br) as test‐bed systems. Our results show that, according to E ST , the SH experienced along these simple reactions fits, in the general case, the trends predicted by a meticulous and rigorous application of chemical intuition. However, steric clash alone should not be considered as the only argument used to explain the easiness of the SN2 reaction over different electrophiles.

Structure‐dependence in initial decomposition of trans‐1,2‐dimethylcyclohexyl isomers: Kinetic exploration and conformational analysis

AbstractTo elucidate the combustion behaviors of trans‐1,2‐dimethylcyclohexyl isomers, their initial decomposition have been explored by employing quantum chemical calculations coupled with transition state theory. All conformational structures and their interconversion mechanisms were studied. Originated from distinct conformers, all accessible transition states were explicitly identified in multiple paths for H‐transfer or β‐scission, and then were carefully used in kinetic predictions. The fairly speedy conformation fairly dominates over decomposition that allows thoroughly evaluating the contribution of various conformers to the final kinetics. Conformational analysis unravels that the most favorable 1,5 H‐transfer is only feasible for one twist‐boat with radical site in axial side chain accompanied by one isoclinal methyl group. The results for β‐scissions are affected by steric energies and substituent effects remained in conformational structures. These findings facilitate to finally figure out the proper kinetic parameters for each decomposition reaction for the implication in kinetic modeling simulation.

Prediction of Second-Order Rate Constants of Sulfate Radical with Aromatic Contaminants Using Quantitative Structure-Activity Relationship Model

Predicting the second-order rate constants between aromatic contaminants and a sulfate radical (kSO4•−) is vital for the screening of pollutants resistant to sulfate radical-based advanced oxidation processes. In this study, a quantitative structure-activity relationship (QSAR) model was developed to predict the values for aromatic contaminants. The relationship between logkSO4•− and three molecular descriptors (electron density, steric energy, and ratio between oxygen atoms and carbon atoms) was built through multiple linear regression. The goodness-of-fit, robustness, and predictive ability of the model were characterized statistically with indicators showing that the model was reliable and applicable. Electron density was found to be the most influential descriptor that contributed the most to logkSO4•−. All data points fell within the applicability domain, and no outliers existed in the training set. The comparison with other models indicates that the QSAR model performs well in elucidating the mechanism of the reaction between aromatic compounds and sulfate radicals.

Interactions of coal pitch with amphoteric polycarboxylate dispersant in coal pitch–water slurry: Experiments and simulations

As the main by-product of coal tar processing, large amounts of coal pitch (CP) are insufficiently utilized. In this study, to realize resource utilization, CP was used to prepare coal pitch–water slurry (CPWS) fuels with the addition of three amphoteric polycarboxylate dispersants (AAD-1, AAD-2, AAD-3). The effects of dispersants on the slurry characteristics were studied. The adsorption of dispersant and the surface properties of CP were also analyzed. Results showed that the AAD-2 with a moderate side-chain length had a better ability to increase the stability and reduce the apparent viscosity of CPWS than others. When the dosage of AAD-2 was 0.5 wt%, the maximum slurry concentration was 53.7 wt%. The adsorption behaviors of three dispersants could be fitted well by the Freundlich model, and the adsorption quantity of AAD-2 was greater than that of two other dispersants. The Zeta potential and wettability of CP were improved to the greatest for AAD-1. To explore the dispersion and stabilization mechanisms, the molecular dynamics simulation and extended DLVO theory were used to discuss the interactions between CP and dispersants, the interaction energy among CP particles. Results showed that the adsorption energy of AAD-2 with CP was the most prominent (-1520.29 kJ/mol), the mobility of water molecules was reduced. Furthermore, in the CPWS with AAD-2, the total interaction energy ΔET was more significant than that of other slurries, which was due to the larger steric hindrance energy from AAD-2. In sum, this research provided an experimental and theoretical basis for preparing slurry with CP and polycarboxylate dispersant.

QSAR Models of Triazine Derivatives Developed Using Quantum-Chemical Energy Descriptors and Topological Descriptors : A Comparative Study

QSAR Models of 25 derivatives of triazine have been developed using quantum chemical and energy descriptors and topological descriptors. The quantum chemical and energy descriptors used are a combination of heat of formation, steric energy, total energy and LUMO energy. The topological descriptors have a combination of connectivity index, shape index, molar refractivity and conformation minimum energy. It was observed that quantum chemical and energy descriptors are able to produce more reliable QSAR model as compared to topological descriptors.

Nano-saturn and ExBox systems: Dominant role of steric, exchange-correlation, and electrostatic effects

To appreciate the origin of host-guest (HG) interactions in nano-Saturn and ExBox systems, we propose to use the density functional theory energy partitioning schemes. One approach includes the kinetic, electrostatic, and exchange-correlation energies, while the contributions of another partitioning scheme are the steric, electrostatic, and quantum effects. It is shown that the steric and exchange-correlation effects as well as the electrostatic interactions are dominant factors contributing to the total interaction energies. Furthermore, an alternative energy partitioning scheme including steric, exchange-correlation, and electrostatic energies is also proposed to accurately accounting for HG interactions in nano-Saturn and ExBox systems.

Solvent contribution to ferrocene conformation: Theory and experiment

Solvent impacts on ferrocene configuration and the nature of its component energies. The measured infrared (IR) spectra of ferrocene (Fc) in the region 400-500 cm−1 exhibit very different profiles in gas phase and in solutions. The present study further explores such the differences in gas phase and in solutions using combined theoretical calculations and experimental measurements. It concentrates on the IR spectra in the region of 400–1200 cm−1 using non-polar (tetrachloromethane (CCl4) and n-hexane (Hex)) and polar (acetonitrile (ACN), dichloromethane (DCM), tetrahydrofuran (THF) and 1,4-dioxane (DOX)) solvents. Six relatively intense normal modes in this region (ν7, ν8,9, ν18, ν22,23, ν30,31 and ν37 at approximately 482, 495, 815, 840, 1006, 1110 cm−1) were obtained. The dependence of the relative energies of the eclipsed and staggered rotamers of Fc on the polarity of the solvent is small. Analysis of the band profile for the vibrational modes in the 480-500 cm−1 region (ν7, ν8,9) using the reaction coordinate model suggests that the energy difference between the eclipsed and staggered rotamers (ΔEe-s solv) may be underestimated by implicit solvent model in the calculations. Further investigation in this direction is warranted. The impact of solvation on Fc configuration is further investigated using energy decomposition analysis (EDA) in a non-polar (tetrachloromethane (CCl4)) and a polar (acetonitrile (ACN)) solvent. These calculations suggest that solvation substantially changes the electrostatic and quantum mechanical Pauli energy contributions to the interaction energy of Fc conformers, which result in a large steric energy in solvents to enhance the dominance of the eclipsed Fc, an observation consistent with the analysis of the bands due to the ν7 and ν8,9 vibrational modes.

Computational study (MM and DFT) on the conformations of some aromatic crown ether rotaxane macrocycles

We examined the preferred conformations of several aromatic crown ether macrocycles containing dibenzo (DB24C8 (1), BMP25C8 (2), BPP34C10 (3)), dinaphtho (2/3DN30C10 (4), 1/5DN38C10 (5)), diphenyl phenanthroline (6) or isophthalamide (7) groups in order to elucidate their preferred conformations and to test the performance of computational methods (molecular mechanics and DFT) in the description of the building blocks of some mechanically interlocked molecules. An exhaustive search for low energy conformations was carried out. The analyses of the geometries of the low-energy conformations of 1–7 revealed that all they have either preformed cavities for adopting substrates, or due to the high flexibility and easy deformability of the macrorings, they have the potential to allow threading of an axle-like molecular component as a slippage step in the formation of a rotaxane structure. Unexpectedly, for one of the macrorings, 4, the geometries of the low-energy conformations differ significantly from the representative conformations of prima facie conformationally similar macrocycles. Contributions from the vibrational entropy term reorder the steric energy lists of conformations in some cases (1, 2, 4, 6), compensating relative steric energies up to 0.9 kcal mol−1. Cluster analysis of the molecular conformations was performed with examining the dependence of the results on the number of torsions for the clustering and the characteristic threshold distances, defining the clustering. All conformations with relative steric energies not exceeding 2.0 kcal mol−1 were examined also with the DFT method (M06-2X functional). In some cases (1 and 2) conformations with relative steric energies ca. 2.0 kcal mol−1 are with the lowest total energies in the corresponding DFT energy lists. These are conformations where the aromatic fragments are facing each other at short distance, ca. 5 Å. We are inclined to conclude that in such cases the DFT models used enhance the dispersion interactions at short distances.

Insilico Anti-COVID Study of New-fangled High Polar Zr(IV) Complexes Functionalized with Resacetophenone and NMP Ligands

A significant issue restricting their commercialization is the short dependability of utilitarian biomolecules. These days, enduring immunizations, antiviral specialists, and anti-infection agents without zero results are intriguing examination subjects. In continuation of our pandemic exploration interest focused on the advancement of the keen antiviral specialist for COVID-19 utilizing heterocyclic metal builds. We describe herein synthesis and structural characterization of two new Zr(IV) complexes containing ligands like resacetophenone (T-R-Zr) (I) and N-methyl-2-pyrrolidone (T-NMP-Zr) (II). The absorption character in a neat solvent, in presence of 4.5 % BSA, and the biological interaction of COVID-19 virus through molecular docking have been summarized taking the scope into coordination chemistry directly or indirectly. The two complexes in 4.5% of BSA display both blue and red shift in peaks corresponds to LCT and MLCT transitions. The molecular docking study of the complex with the crystal structure of SARS-Coronavirus-2 (PDB: 6LU7) shows strong polar interaction with various amino acids present in the spike protein. The complex shows excellent binding energies ranges in-7.0 and -4.9 kcal mol-1, respectively. This makes them potential lead compounds for development into candidates against the SARS-Coronavirus-2. The absorption spectral behavior insolvent and in 4.5 % BSA has been found to show the importance of our complex in biological application especially in COVID-19 treatment studies. Furthermore, we investigated the basic energies like potential and steric energy of the complex through Gaussian energy calculations.

Insilico Anti-COVID Study of New-fangled High Polar Zr(IV) Complexes Functionalized with Resacetophenone and NMP Ligands

A significant issue restricting their commercialization is the short dependability of utilitarian biomolecules. These days, enduring immunizations, antiviral specialists, and anti-infection agents without zero results are intriguing examination subjects. In continuation of our pandemic exploration interest focused on the advancement of the keen antiviral specialist for COVID-19 utilizing heterocyclic metal builds. We describe herein synthesis and structural characterization of two new Zr(IV) complexes containing ligands like resacetophenone (T-R-Zr) (I) and N-methyl-2-pyrrolidone (T-NMP-Zr) (II). The absorption character in a neat solvent, in presence of 4.5 % BSA, and the biological interaction of COVID-19 virus through molecular docking have been summarized taking the scope into coordination chemistry directly or indirectly. The two complexes in 4.5% of BSA display both blue and red shift in peaks corresponds to LCT and MLCT transitions. The molecular docking study of the complex with the crystal structure of SARS-Coronavirus-2 (PDB: 6LU7) shows strong polar interaction with various amino acids present in the spike protein. The complex shows excellent binding energies ranges in-7.0 and -4.9 kcal mol-1, respectively. This makes them potential lead compounds for development into candidates against the SARS-Coronavirus-2. The absorption spectral behavior insolvent and in 4.5 % BSA has been found to show the importance of our complex in biological application especially in COVID-19 treatment studies. Furthermore, we investigated the basic energies like potential and steric energy of the complex through Gaussian energy calculations.

Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential.

Copper(II) and zinc(II) complexes with clinically used antifungal drug fluconazole (fcz), {[CuCl2(fcz)2].5H2O}n, 1, and {[ZnCl2(fcz)2]·2C2H5OH}n, 2, were prepared and characterized by spectroscopic and crystallographic methods. The polymeric structure of the complexes comprises four fluconazole molecules monodentately coordinated via the triazole nitrogen and two chlorido ligands. With respect to fluconazole, complex 2 showed significantly higher antifungal activity against Candida krusei and Candida parapsilosis. All tested compounds reduced the total amount of ergosterol at subinhibitory concentrations, indicating that the mode of activity of fluconazole was retained within the complexes, which was corroborated via molecular docking with cytochrome P450 sterol 14α-demethylase (CYP51) as a target. Electrostatic, steric and internal energy interactions between the complexes and enzyme showed that 2 has higher binding potency to this target. Both complexes showed strong inhibition of C. albicans filamentation and biofilm formation at subinhibitory concentrations, with 2 being able to reduce the adherence of C. albicans to A549 cells in vitro. Complex 2 was able to reduce pyocyanin production in Pseudomonas aeruginosa between 10% and 25% and to inhibit its biofilm formation by 20% in comparison to the untreated control. These results suggest that complex 2 may be further examined in the mixed Candida-P. aeruginosa infections.

Targeting Beta-Blocker Drug-Drug Interactions with Fibrinogen Blood Plasma Protein: A Computational and Experimental Study.

In this work, one of the most prevalent polypharmacology drug–drug interaction events that occurs between two widely used beta-blocker drugs—i.e., acebutolol and propranolol—with the most abundant blood plasma fibrinogen protein was evaluated. Towards that end, molecular docking and Density Functional Theory (DFT) calculations were used as complementary tools. A fibrinogen crystallographic validation for the three best ranked binding-sites shows 100% of conformationally favored residues with total absence of restricted flexibility. From those three sites, results on both the binding-site druggability and ligand transport analysis-based free energy trajectories pointed out the most preferred biophysical environment site for drug–drug interactions. Furthermore, the total affinity for the stabilization of the drug–drug complexes was mostly influenced by steric energy contributions, based mainly on multiple hydrophobic contacts with critical residues (THR22: P and SER50: Q) in such best-ranked site. Additionally, the DFT calculations revealed that the beta-blocker drug–drug complexes have a spontaneous thermodynamic stabilization following the same affinity order obtained in the docking simulations, without covalent-bond formation between both interacting beta-blockers in the best-ranked site. Lastly, experimental ultrasound density and velocity measurements were performed and allowed us to validate and corroborate the computational obtained results.

The Origin of the Chiral gauche-Conformation Preferences in Halomethyl Methyl Ethers. A Hybrid-Density Functional Study and Natural Bond Orbital Interpretation

The effects of the stereoelectronic interaction on the structural and conformational properties of fluoromethyl methyl ether (1) and its analogues containing Cl (2), Br (3), and I (4) atoms were investigated by means of hybrid-density functional based method (B3LYP/Def2-TZVPP) and natural bond orbital (NBO) interpretation. Consistent with the reported experimental data, the chiral gauche conformations of compounds 1–4 are more stable than their corresponding anti conformations. The results showed that the energy barriers of the racemization processes of the chiral gauche-conformations of compounds 1–4 via the plane symmetrical anti conformations are smaller than the plane symmetrical eclipsed transition structures. According to the NBO analysis, the hyperconjugative generalized anomeric effect (HCGAE) increased from compound 1 to compound 4, which explains the increase of the energy discrepancy between their corresponding chiral gauche- and plane symmetrical anti-conformations. In contrast to the trend for the HCGAE, the determined dipole moment discrepancy between the chiral gauche- and plane symmetrical anti-conformations (µanti–µgauche) reduced from compound 1 to compound 4. This fact reveals that there is no correlation between the variations of the conformational preferences in compounds 1–4 and the electrostatic effects associated with the dipole–dipole interactions. There is an excellent agreement between the racemization energy barriers and the proportion between the GAE for compounds 2–4 and compound 1 (i.e., GAEx/GAE1) as well as the difference between the Wiberg Bond Indexes of C1–O2 bonds (Δ[WBIanti-gauche(C1–O2)]). The associations between the HCGAE, pairwise steric exchange energies (PSEE), WBI, dipole moments, orbital integrals, structural parameters, and conformational behaviors of compounds 1–4 have been studied.

Dispersion mechanism of coal water slurry prepared by mixing various high-concentration organic waste liquids

High-concentration organic waste liquids have complex components and their treatment is difficult. These liquids also contain hydrophobic organic pollutants. The preparation of waste liquid coal water slurry (WCWS) can aid with environmental protection and resource utilization. In this study, xanthan gum was selected from 11 types of additives because it overcomes the problem of solution incompatibility during the mixing of various high-concentration organic waste liquids. The experimental results showed that with 0.08 wt% addition of xanthan gum, no stratification occurred in the mixed waste liquid and the apparent viscosity of the WCWS was 921.1 mPa∙s. In this study, the role of xanthan gum was studied, and the effect of its addition on the coal particle surface was characterized by zeta potential and contact angle measurement. In addition, various interaction energies in the WCWS system were calculated using the extended DLVO theory. The results showed that xanthan gum introduced steric hindrance interaction energy into the WCWS system, enabling the system to be stably dispersed.

A positive and energy stable numerical scheme for the Poisson–Nernst–Planck–Cahn–Hilliard equations with steric interactions

In this work, we consider numerical methods for the Poisson–Nernst–Planck–Cahn–Hilliard (PNPCH) equations with steric interactions, which correspond to a non-constant mobility H−1 gradient flow of a free-energy functional that consists of electrostatic free energies, steric interaction energies of short range, entropic contribution of ions, and concentration gradient energies. We propose a novel energy stable numerical scheme that respects mass conservation and positivity at the discrete level. Existence and uniqueness of the solution to the proposed nonlinear scheme are established by showing that the solution is a unique minimizer of a convex functional over a closed, convex domain. The positivity of numerical solutions is further theoretically justified by the singularity of the entropy terms, which prevents the minimizer from approaching zero concentrations. A further numerical analysis proves discrete free-energy dissipation. Extensive numerical tests are performed to validate that the numerical scheme is first-order accurate in time and second-order accurate in space, and is capable of preserving the desired properties, such as mass conservation, positivity, and free energy dissipation, at the discrete level. Moreover, the PNPCH equations and the proposed scheme are applied to study charge dynamics and self-assembled nanopatterns in highly concentrated electrolytes that are widely used in electrochemical energy devices. Numerical results demonstrate that the PNPCH equations and our numerical scheme are able to capture nanostructures, such as lamellar patterns and labyrinthine patterns in electric double layers and the bulk, and multiple time relaxation with multiple time scales. The multiple time relaxation dynamics with metastability take long time to reach an equilibrium, highlighting the need for robust, energy stable numerical schemes that allow large time stepping. In addition, we numerically characterize the interplay between cross steric interactions of short range and the concentration gradient regularization, and their impact on the development of nanostructures in the equilibrium state.

Theoretical Analysis of Stereoelectronic Effects in the 2,4,6-Trihalo-1,3,5-trioxane and 2,4,6-Trihalo-1,3,5-trithiane Conformers

This research aimed at exploring the conformers stabilities of 2,4,6-trihalo-1,3,5-trioxane and 2,4,6-trihalo-1,3,5-trithiane molecules at the LC-wPBE/6-311+G(d, p) theory level. To this goal, estimations of the total energies and frontier orbitals energies of the axial and equatorial conformations were first done for the afore-mentioned molecules. C–E (E = O, S), C–X (X = F, Cl), and C–H bonds lengths were calculated and these variations were explained with negative hyperconjugative anomeric effects. In addition, QTAIM analysis was used to illustrate the character of these bonds. The partitioning of the total electronic energy E(tot) into Lewis EL and non-Lewis ENL parts was performed using the concept of natural bond orbital (NBO) analysis. Then, the natural Coulomb electrostatic (NCE) potential energies, total energies into Lewis components, and total steric energies were estimated. Proton chemical shift and C–H spin–spin coupling values (J(C–H)) of the studied molecules were calculated.

Synthesis of sodium polyacrylate copolymers as water-based dispersants for wet ultrafine grinding of cobalt aluminate particles

Sodium polyacrylate copolymers, i.e., polymethyl methacrylate-methacrylic acid-2-acrylamido-2-methylpropane sulfonic acid-hydroxyethyl methacrylate (PMASHS) were synthesized with polymethacrylic acid-2-acrylamido-2-methyl propane sulfonic acid-hydroxyethyl methacrylate (PASH) as water-based dispersants for ultrafine grinding of cobalt aluminate (CoAl2O4) particles in a stirred bead mill. The product size/size distribution, suspension rheological properties, electrokinetic potential and adsorption behavior were analyzed by laser particle size analysis, rheometry, thermogravimetry and electrokinetic potential measurement, respectively. Dispersant PMASH1 used for grinding the pigment particles for 120 min gives an increased product fineness with a narrower particle size distribution. This is possibly due to the presence of solvated chains of dispersant PMASH1 on the particle surface generating a proper steric hindrance energy between the particles. Besides, the breakage behavior of CoAl2O4 particles in ultrafine grinding was also discussed by selection and breakage functions from population balance modeling, indicating that the addition of dispersant PMASH1 in ultrafine grinding has a greater grinding efficiency. The breakage mechanism of the pigment particles in the bead mill is mainly abrasion, accompanied by compression.

What Is the Main Feature Distinguishing the Through-Space Interactions in Cyclophanes from Their Aliphatic Analogues?

Classical cyclophanes with two benzene rings have been compared with cyclophanes with one benzene ring replaced with an aliphatic part and aliphatic compounds, which are cyclophane analogues. Analysis of geometry, atomic charges, and aromatic and steric energy and investigation of intramolecular noncovalent interactions and charge mobility show that there is no special feature that distinguishes the classical cyclophanes from aliphatic analogues, so the definition of cyclophanes can be extended to other compounds.

Anionic behavior and single-molecule crystal in fullerene confinements: A contribution from DFT energy decomposition and cooperativity analyses.

The recently proposed systems of various anions (A) confined inside C60 , A- @ C60 , which in turn behave as large and stable anions, (A @ C60 )- , can find potential applications in various fields. On the other hand, it has earlier been shown that from the dihalogens (X2 ) encapsulated C60 , X2 @ C60 , only F2 @ C60 can be introduced as a system in which the cage acts as a cation C60 + and interacts with an endohedral anion, F2 - , forming the F2 - @ C60 + as a single-molecule crystal compound. In this work, two density functional theory energy decomposition analysis (EDA) schemes, where in one of them the noninteracting kinetic, electrostatic, and exchange-correlation energies come into play while another scheme, called as EDA-SBL, includes the steric, electrostatic, and quantum effects as essential ingredients (S. Liu, J. Chem. Phys. 2007, 126, 244103), are utilized to find out what energetic components govern the unique characteristics of the (A @ C60 )- and X2 @ C60 confinements. It is shown that the noninteracting kinetic energy and steric energies have important contributions to the total interaction energies for the considered systems. However, there are other confinements for which the electrostatic and exchange-correlation contributions play also imperative roles. Furthermore, we find reasonable correlations between interaction energies and their components as well as the energetic components themselves, leading to an alternative EDA scheme including the noninteracting kinetic, steric, and electrostatic energies for investigations on other endohedral fullerenes. Extending our analyses to large size confinements, Cl- @ Cn with n up to 90 as illustrative examples, the quantitative cooperativity concept is also explored, where the positive and negative cooperativity profiles unveil a specific size of the anionic confinements to form the most stable large anion.

Bond strength and computational analysis for silane coupling treatments on the adhesion of resin block for CAD/CAM crowns.

The purposes of this study were to evaluate the shear bond strength and perform the computational analysis for silane coupling treatments on the adhesion between CAD/CAM composite resin and resin cement. As silane coupling agents, γ-methacryloyloxy propyltrimethoxysilane, 8-methacryloyloxyoctyl trimethoxysilane, and 3-methacryloyloxypropyl trichlorosilane were used. The shear bond strengths were influenced by the silane coupling agent used, its application method, and acid addition. There was no correlation between the contact angle and shear bond strengths. The steric energy difference between a silane coupling agent and its corresponding hydrolyzed trisilanol compound, ∆E, was calculated by the molecular mechanics method. There was a moderate or strong linear correlation between ∆E and shear bond strengths in treatment without acid addition and a weak correlation between them in treatment with acid addition. Computational analysis could suggest the different path of silane coupling treatments of CAD/CAM composite resin in the presence or absence of acid.