B3LYP Density Functional Theory Research Articles

Spectroscopic investigations (FTIR, UV-VIS, NMR) and DFT calculations on the molecular structure of Nω-Nitro-L-arginine

The spectroscopic properties of Nω-nitro-l-arginine were investigated by FT-IR, UV-VIS, and 1H NMR spectra. Geometrical parameters and energies were calculated using the density functional theory (DFT) B3LYP method with the 6-311G basis set. Geometrical optimization of the molecule has been performed, vibrational spectra have been calculated, and fundamental vibrations have been determined from the total energy distribution (TED) of the vibrational modes. The HOMO-LUMO analysis is carried out for various electric fields (0.0–0.025 A−1). The HOMO-LUMO gap is decreased while increasing the electric field. The calculated quantum chemical parameters are calculated and correlated to the inhibition efficiency, A Mullliken population was also important for determining local reactivity by indicating reactive centers and identifying potential nucleophilic and electrophilic attack sites. Charge transfer occurs inside the compound based on the HOMO LUMO gap. Calculations of DFT were evaluated in their ability to predict inhibition efficiency.

Design of new visible light Pt photocatalyst based on the TDDFT study of properties of transition metal complexes

AbstractVisible light photocatalysis has been paid a lot of attention because of its green and lower energy consuming. To trigger a reaction via energy transfer, a potential visible light photocatalyst not only has absorption under visible light but also needs a high triplet excitation energy. In this scene, the density functional theory B3LYP methods were used to investigate the properties of transition metal complex photocatalysts and design new potential visible light photocatalysts. The calculation result shows that the studied Ir complexes have a relatively high ET values (energy gap between the triplet excited state and ground state). The introduction of electron‐donating groups to Ir complexes causes a slight redshift in the absorption spectrum. Moreover, the electronic structure and atomic radius of the central metal atom have a great influence on the properties of those complexes of “fac‐M(ppy)3” (transition metal complexes with facial structure and three ppy ligands, M = Pt, Ni, Rh, Ru, Fe). Based on the study of transition metal complexes, new visible light Pt complex photocatalysts that have both good absorption under visible light and high ET value have been designed here. The designed new Pt complexes are expected to be potential candidates as visible light photocatalysts.

A combined experimental and theoretical study of alkyl 2-(3-benzoyl-4‑hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)acetates: Synthesis, X-ray crystallography and DFT

Benzothiazine derivatives belongs to an important class of organic compounds with a wide range of application in the field of biotechnology and medicinal chemistry, and many of its derivatives have been considered in drug discovery. A series of three alkyl 2-(3-benzoyl-4‑hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)acetates (3a–c) were synthesized from the sulfonimidamides through multistep reactions. The molecular geometry of these compounds has been investigated with the help of X-ray crystallography and quantum mechanical calculations. The molecular structural optimization and structural properties were calculated using the Density Functional Theory method and B3LYP hybrid functional with 6–311+G* basis set. Non-covalent interactions studies, energetics and reactivity properties of 3a-c compounds have been explored through local and global reactivity descriptors, UV-Visible spectral analysis and molecular electrostatic potential illustrations. It is found that the compound 3b is more reactive than others because of its lowest frontier molecular orbital energy gap (ΔE=3.46 eV) and low chemical hardness (η=0.23eV) than others. Furthermore, the investigations of Non-linear optical properties and thermodynamic parameters have also been carried out which shows that these compounds can be used as a non-linear optical material in the field of telecommunication and information technologies.

Analeptic activity of 2-Hydroxyl-5-Nitrobenzaldehyde: Experimental, DFT studies, and in silico molecular docking approach

This study was carried out to evaluate the spectroscopic, molecular properties, and in silico biological assessment of 2-Hydroxyl-5-Nitrobenzaldehyde (NSA) characterized by FT-IR, UV, NMR spectral, and first-principle density functional theory (DFT). The optimized molecular geometry, the vibrational wavenumbers, and infrared intensities activities were calculated by using the density functional theory (DFT) B3LYP method with a 6–311++G(d,p) basis set. The detailed interpretation of the vibrational spectra was assigned by VEDA program. The results of NBO analysis show that LP(3)O12 and LP(2)O13 bonding orbitals participated as donors and the π*N10–O11 and π*C2–C3 antibonding orbitals as acceptors in all the four phases understudy with occupancies in the range of 1.45453, 1.85287 leading to the stabilization energy of 160.60 and, 30.55 kcal/mol, which results in intramolecular charge transfer leading to the stabilization of the molecule. Moreover, Drug likeness properties of NSA are predicted. The predicted ADMET properties showed high gastrointestinal absorption, does not permeant the brain–blood barrier, nor any Cytochrome P450 inhibition (1A2, 2C19, 2C9, 2DA, 3A4, and 3A4) without violating any of the Lipinski rules. The result from the molecular docking showed that NSA has the highest negative mean binding affinity of −5.71 kcal/mol, followed by CFN and EDE which are approximately equal at −5.176 and −5.004 kcal/mol respectively and added to a more significant hydrogen bond with amino acids residues of the selected receptor proteins. Therefore, it could be said that NSA is a potential analeptic agent.

Application of Polarisable Continuum Modelling to assess Minoxidil solubility in mixed solvents

ABSTRACT Experimental solubility of minoxidil was obtained in binary aqueous mixtures of ethanol, methanol and acetonitrile at 298.2 K. The effects of pH and micellisation were investigated on the solubility of the drug. Experimental solubility data was correlated by three co-solvency models, i.e. Yalkowsky, CNIBS/R-K, and the modified Wilson model. Density functional theory and hybrid functional B3LYP method was used with Polarisable Continuum Model (PCM) to correlate the experimental solubility data in various mass fractions of the binary solvent mixtures. We report the results of solute–solvent interaction energy as free energy of solvation (∆G sol ) of minoxidil in various mass fractions of ethanol + water mixtures. Total electrostatic energy, dipole moment, total Gibbs free energy and dielectric constant (ε) of minoxidil were also investigated.

Adhesion Strength Calculations of Tricalcium Phosphate Application on Titanium Implant by First Principle Methods

The focus of this research is to propose a method of calculating the adhesive strength of a nano-crystalline structure of tricalcium phosphate, a material used in dentistry to cover a titanium tooth implant to increase osseointegration, which is the conduciveness of its mating to bone, by using Density Functional Theory (DFT). The nano-crystalline structure of tricalcium phosphate has shown to increase osseointegration between the coating and the bone. While fast osseointegration is most attractive, it is important to have a strong adhesive bond between the coating and the titanium implant. A measure of the coating-to-substrate (titanium implant) binding energy is the energy of this bond. We suggest a theoretical method how to calculate the adhesion strength of tricalcium phosphate coating on titanium substrate, using ab initio calculations. We slowly “built up” Tricalcium Phosphate by way of calculating the binding energy between its constituent parts and titanium. We used the Gaussian09 DFT B3LYP with a basis set of 6-31G to structurally analyze the bond lengths, bond angles, dihedral angles, and point charges to understand the interactions of these substances and how they contribute to the strength.

Theoretical studies on molecular conformers and infrared spectra of triethylamine

<sec>Based on the method of density functional theory B3LYP with a 6-311++G(d, p) basis set, the potential energy surface of conformational isomerization along the two-dimensional coordinates formed by the dihedral angles <i>ϕ</i><sub>1</sub>(C9N1C2C5) and <i>ϕ</i><sub>2</sub>(C16N1C9C12) in a range of –180°–180° is investigated. And 12 ground state conformers of triethylamine are identified. Furthermore,with the second-order Moller-Plesset perturbation theory</sec><sec>MP2 on the same basis set level, the structures of six lower-energy conformers are optimized and their energy values are estimated. The results show that G1 and G1' with C<sub>3</sub> symmetry are the most stable conformers and G4 and G4' with new methyl orientations are identified. In addition, some vibrational modes in the infrared spectra of G1–G4 are assigned and discussed. The infrared spectra of G1–G4 show that the intensity is weak in a range of 0–1600 cm<sup>–1</sup>, while the intensity is strong in a range of 2800–3300 cm<sup>–1</sup>. The characteristic vibration modes such as umbrella vibration and CH stretching vibration are assigned. The average shift of the corresponding infrared peaks on different conformations is estimated at less than 20 cm<sup>–1</sup>.</sec>

DFT Analysis of Ions Conductivity of Proline in Certain Solvents: Calculation of Association Parameters

Proline (Pro.) is non-essential amino acid, and it is from the amino acids which the human’s body can synthesize it, from L-glutamate. It is studied in the temp. range from 288.16 to 313.16 K at 5 K by conductivities in H2O, and methanol. The Kohlrausch equations was used to find out pattern of electrolyte, the curve indicate pro. was weakly associated in various temperatures and solvents. The Lee-Wheaton equation was us to calculation the Equivalent conductance at infinite dilution (Λο), The association constant (Ka) and distance parameter (R). The values of (Λο), (Ka), and (R) differ from solvent to another depending on the interactions in solution. The molecular modeling, geometry optimization and characterization of pro. has been performed using semi empirical method, and all theoretical parameters was calculated by using Austin Model 1 (AM1), and used density functional theory (DFT) B3LYP method by using 6-311G bases set.

Computational analyses of the vibrational spectra of fentanyl, carfentanil and remifentanil

The infrared (IR) spectra of fentanyl, carfentanil and remifentanil, and protonated salts, are computed using quantum chemistry methods. New experimental FTIR spectra are also reported and compared to the calculations. The accuracy of two density functional theory methods, B3LYP and M06-2X, are tested against higher level theories (MP2) and the experimental data. Gas phase IR spectra are calculated for both the neutral and protonated molecules in order to compare with the experimental data measured for various salts of fentanyl and its analogues. Key vibrational modes are selected and studied in detail using a vibrational mode locality calculation. The main contributing atomic movements in these vibrational modes are identified.

Molecular Docking and Quantum Chemical Computations of 4-Chloro-2-[(furan-2-ylmethyl)amino]-5-sulfamoylbenzoic Acid Based on Density Functional Theory

Quantum computational calculations of energies and geometries of 4-chloro-2-[(furan-2-ylmethyl)amino]-5-sulfamoylbenzoic acid have been performed by DFT level of theory using B3LYP/6-31G(d,p) basis set. The solid phase FT-Raman and FT-IR spectra of the Furosemide compound were recorded in the region 4000 cm−1 to 400 cm−1 and 4000 cm−1 to 400 cm−1 respectively. The molecular geometry, harmonic vibrational frequencies and bonding features of 4-chloro-2-[(furan-2-ylmethyl)amino]-5-sulfamoylbenzoic acid in the ground state have been calculated by using density functional theory (DFT) B3LYP method with standard 6–31 G(d,p) basis set. The scaled theoretical wavenumber showed very good agreement with the experimental values. The vibrational assignments were performed on the basis of the total energy distribution (TED) of the vibrational modes. Stability associated with molecule as a result of hyperconjugative interactions, charge delocalization has been analyzed utilizing Natural Bond Orbital (NBO) analysis through the use of B3LYP/6-31G(d,p) technique. The outcomes reveal that electron density (ED) within the σ* and π* orbitals which are antibonding second-order delocalization energies E (2) confirm the occurrence of intramolecular charge transfer (ICT) inside the molecule. Hirshfield surface analysis and Fukui functions calculation were also performed. From the calculations the first order hyperpolarisability was found to be 3.136 × 10−30esu. The molecule orbital contributions have been analyzed utilizing the total (TDOS), partial (PDOS), and overlap population (OPDOS) density of states. A molecular docking study has supported the anticonvulsant activity of the Furosemide molecule.

NH Stretching Frequencies of Intramolecularly Hydrogen-Bonded Systems: An Experimental and Theoretical Study.

The vibrational NH stretching transitions in secondary amines with intramolecular NH···O hydrogen bonds were investigated by experimental and theoretical methods, considering a large number of compounds and covering a wide range of stretching wavenumbers. The assignment of the NH stretching transitions in the experimental IR spectra was, in several instances, supported by measurement of the corresponding ND wavenumbers and by correlation with the observed NH proton chemical shifts. The observed wavenumbers were correlated with theoretical wavenumbers predicted with B3LYP density functional theory, using the basis sets 6-311++G(d,p) and 6-31G(d) and considering the harmonic as well as the anharmonic VPT2 approximation. Excellent correlations were established between observed wavenumbers and calculated harmonic values. However, the correlations were non-linear, in contrast to the results of previous investigations of the corresponding OH···O systems. The anharmonic VPT2 wavenumbers were found to be linearly related to the corresponding harmonic values. The results provide correlation equations for the prediction of NH stretching bands on the basis of standard B3LYP/6-311++G(d,p) and B3LYP/6-31G(d) harmonic analyses, with standard deviations close to 38 cm−1. This is significant because the full anharmonic VPT2 analysis tends to be impractical for large molecules, requiring orders of magnitude more computing time than the harmonic analysis.

Nonenzymatic Deamidation Mechanism on a Glutamine Residue with a C-Terminal Adjacent Glycine Residue: A Computational Mechanistic Study

The deamidation of glutamine (Gln) residues, which occurs non-enzymatically under physiological conditions, triggers protein denaturation and aggregation. Gln residues are deamidated via the cyclic glutarimide intermediates to l-α-, d-α-, l-β-, and d-β-glutamate residues. The production of these biologically uncommon amino acid residues is implicated in the pathogenesis of autoimmune diseases. The reaction rate of Gln deamidation is influenced by the C-terminal adjacent (N +1) residue and is highest in the Gln-glycine (Gly) sequence. Here, we investigated the effect of the (N + 1) Gly on the mechanism of Gln deamidation and the activation barrier using quantum chemical calculations. Energy-minima and transition-state geometries were optimized by the B3LYP density functional theory, and MP2 calculations were used to obtain the single-point energy. The calculated activation barrier (85.4 kJ mol−1) was sufficiently low for the reactions occurring under physiological conditions. Furthermore, the hydrogen bond formation between the catalytic ion and the main chain of Gly on the C-terminal side was suggested to accelerate Gln deamidation by stabilizing the transition state.

Experimental, spectroscopic and theoretical investigation of (+)-(R)-5-[1-(Benzenesulfonamido)-2-phenylethyl]-4-phenethyl-2,4-dihydro-3H-1,2,4-triazole-3-thione

In this study, an enantiomerically pure triazole derivative, namely, (+)-(R)-5-[1-(benzenesulfonamido)-2-phenylethyl]-4-phenethyl-2,4-dihydro-3H-1,2,4-triazole-3-thione was successfully synthesized in high yield and characterized by spectroscopic techniques (FT-IR and UV–Vis) and single crystal X-ray diffraction analysis. Hirshfeld surface (HS) analysis revealed the nature of intermolecular contacts, the fingerprint plots, and molecular surface contours. All theoretical computations were calculated using density functional theory (DFT) B3LYP method with the help of 6–311G(d,p) basis set. Chemical activity descriptors were studied for global (HOMO, LUMO, hardness, and softness parameters) and local (MEP, Fukui function, net charges). The stability of the molecule arising from hyper conjugative interactions, charge delocalization was analyzed by using natural bond orbital analysis (NBO) and in the continuation of the study, nonlinear optical properties were examined.

Physicochemical Characterization of the Loganic Acid-IR, Raman, UV-Vis and Luminescence Spectra Analyzed in Terms of Quantum Chemical DFT Approach.

The molecular structure and vibrational spectra of loganic acid (LA) were calculated using B3LYP density functional theory, the 6–311G(2d,2p) basis set, and the GAUSSIAN 03W program. The solid-phase FTIR and FT-Raman spectra of LA were recorded in the 100–4000 cm−1 range. The assignment of the observed bands to the respective normal modes was proposed on the basis of the PED approach. The stability of the LA molecule was considered using NBO analysis. The electron absorption and luminescence spectra were measured and discussed in terms of the calculated singlet, triplet, HOMO, and LUMO electron energies. The Stokes shift derived from the optical spectra was 20,915 cm−1.

In English

It is known that titanium dioxide as photocatalyst has significant drawback - limited absorption spectrum in the ultraviolet region makes it impossible to use solar energy. To expands the absorption spectrum of TiO2, the doping of impurities (metal, non-metal, etc.) were used. They affected the electronic structure and spectral characteristics of TiO2. The aim of our work was to investigate the influence of tin impurities on spectral characteristics of titanium dioxide using experimental and theoretical methods. The TiO2 powders modified by different amount of tin (Sn/TiO2) were synthesized by sol-gel method. The samples were characterized by SEM, EDX, FT-IR and UV-VIS spectroscopy. It has been found that Sn/TiO2 consists of fragmented agglomerates in the range of 5–10 mm. EDX spectroscopy prove that powders include Ti, O and Sn elements. Modification of titanium dioxide with tin leads to band gap narrowing of samples, which explains by insertion of Sn atoms into crystal lattice of titanium dioxide, because Ti4+ and Sn4+ ions radii are close. The band gap values increased with increasing of tin content. The work also analyzes the vibrational spectra of Sn/TiO2 both experimentally and theoretically. In order to interpret the results obtained, quantum chemical calculations on the spatial and electronic structures of cluster models of titanium dioxide (anatase) with inserted tin atoms using the density functional theory B3LYP method and the basis set 6-31G (d, p) were carried out and the corresponding FT-IR spectra have been simulated. By comparing the experimental and theoretical results, the influence has been analyzed of the number and arrangement of impurity tin atoms in clusters on the observed IR spectra of the samples. This makes it possible to forgive the most probable structural motives of titanium dioxide particles doped with tin atoms, as well as to establish the fact of the presence of tin atoms in the samples. Based on the comparison of the IR spectra of samples with different numbers of tin atoms, it is possible to quantify their composition.

A comparison of three DFT exchange-correlation functionals and two basis sets for the prediction of the conformation distribution of hydrated polyglycine.

The performance of three density functional theory (DFT) exchange-correlation functionals, namely, Perdew-Burke-Ernzerhof (PBE), BP86, and B3LYP, in predicting conformational distributions of a hydrated glycine peptide is tested with two different basis sets in the framework of adaptive force matching (AFM). The conformational distributions yielded the free energy profiles of the DFT functional and basis set combinations. Unlike traditional validations of potential energy and structural parameters, our approach allows the free energy of DFT to be validated. When compared to experimental distributions, the def2-TZVP basis set provides better agreement than a slightly trimmed aug-cc-pVDZ basis set. B3LYP is shown to be better than BP86 and PBE. The glycine model fitted against B3LYP-D3(BJ) with the def2-TZVP basis set is the most accurate and named the AFM2021 model for glycine. The AFM2021 glycine model provides better agreement with experimental J-coupling constants than C36m and ff14SB, although the margin is very small when compared to C36m. Our previously published alanine model is also refitted with the slightly simplified AFM2021 energy expression. This work shows good promise of AFM for developing force fields for a range of proteinogenic peptides using only DFT as reference.

Catalytic activity of 2-phenyl pyridine palladacycle and its structural studies using DFT calculations

2-phenyl pyridine palladacycle [Pd (κ2 -N, C-C11H8N) (O3SC7H7)-{P (C6H5)3}] (1) was tested for the catalytic activity in the vinylation of 3-Bromo-benzophenone to give 3-Vinyl benzophenone, a precursor for the synthesis of Ketoprofen an anti-inflammatory drug. The effect of various reaction parameters such as temperature, palladacycle loading, ethylene pressure and material balance for the vinylation reaction was studied. The palladacyle (1) exhibited excellent catalytic activity with a TOF of 4842 h-1 in the vinylation reaction. The structural properties of palladacycle (1) were studied by employing the B3LYP density functional theory with SDD and 6-311++G (d, p) basis sets at the Gaussian 09 package of programs. The computed density functional theory (DFT) structural parameters (bond lengths and bond angles) of the optimized geometry using the B3LYP/6-311G basis set were found to compare favourably with those of the X-ray crystal structure.

Anti-microbial activity, molecular profiling, electronic properties and molecular docking investigations of 5–[1-hydroxy–2–(isopropylamino)ethyl] benzene–1,3–diol

This study was carried out to evaluate the of 5-[1-hydroxy–2–(isopropylamino)ethyl]benzene-1,3-diol (5H2IB3D) was characterized by FT-IR, FT-Raman, UV, 1H NMR and 13C NMR spectral analysis. The optimized molecular geometry, the vibrational wave numbers, the infrared intensities and the Raman scattering activities were calculated by using density functional theory (DFT) B3LYP method with 6–311++G(d,p) basis set. The detailed interpretation of the vibrational spectra was assigned by VEDA program. The calculated HOMO and LUMO energies show that charge transfer within the headline molecule. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital analysis (NBO). The first order hyperpolarizability, Molecular electrostatic potential (MEP) and Fukui functions were also performed. Wave functional study like electron localization function (ELF) and localized orbital locator (LOL) are analyzed. Moreover, Drug likeness properties of 5H2IB3D are predicted. To study the biological activity of the investigation of the headline molecule, molecular docking was done to identify the hydrogen bond lengths and binding energy with cardiovascular analeptic proteins.

Quantum-chemical study on the relative stability of sildenafil tautomers

The tautomeric equilibrium of sildenafil molecule was theoretically studied using B3LYP and M06-2X density functional theory (DFT) methods in connection with aug-cc-pVDZ correlation consistent basis set. Calculations were performed for gas phase and water solution conditions modelled by polarizable continuum model (PCM). Three tautomeric forms are possible. Two keto forms: A — where the tautomeric proton in more distant from carbonyl group and B — where it is closer, and one enol form denoted, C. Both DFT methods qualitatively give similar tautomer stability order: B > A > C. The B tautomer is dominant in gas phase and water environment, whereas the C tautomer is too high in energy to be present in the tautomeric mixture. Regarding the A tautomer, it is not present in the gas phase but is present in small amounts in water solution. According to B3LYP/aug-cc-pVDZ, the relative Gibbs-free energies for A and C relative to B are 10.05 kcal/mol and 11.91 kcal/mol for gas phase and 5.49 kcal/mol and 12.49 kcal/mol for water solution. According to M06-2X/aug-cc-pVDZ, the relative Gibbs-free energies for A and C are 9.12 kcal/mol and 10.60 kcal/mol for gas phase and 4.27 kcal/mol and 10.23 kcal/mol for water solution. Therefore, for in vivo conditions, we expect that the B tautomer is dominant, and there may exist small amounts of the A tautomer. The C enol tautomer is not present at all. This picture is very different from the parent tautomeric system: 4-hydroxypyrimidine/4-pyrimidinone where the C enol tautomer is less stable than keto B only by about 1 kcal/mol in the gas phase and the A keto tautomer is the least stable and not present in the tautomeric mixture. In order to understand these differences, we performed additional calculations for a series of parent molecules starting from 4-hydroxypyrimidine/4-pyrimidinone, going through two in-between model molecules and ending at Sildenafil molecule. We found that the most important reasons of C form destabilization are dearomatization of the 6-membered ring caused by the fusion with pyrazole ring, lack of strong intramolecular hydrogen bond in C form of sildenafil and presence of destabilizing steric interaction of oxygen and nitrogen atoms of two 6-memberd rings in this tautomer.

Tracking the deprotonation site of dehydroandrographolide with electrospray ionization mass spectrometry by deuteration.

Dehydroandrographolide (DA) is a diterpene compound of biological interest that contains one α,β-unsaturated lactone group and two hydroxy groups. In the ESI (electrospray ionization) negative ion mode mass spectral analysis of 15-dideuterodehydroandrographolide (15-D2 -DA), the deuterium nucleus at the γ position of the α,β-unsaturated lactone was more easily dedeuterated than deprotonation of the protons from the hydroxy groups. Exploring the rationality of deuteration as a tool for deprotonation position tracking is significant for gas-phase acidity. The mass spectra of DA and 15-D2 -DA in positive and negative ion mode were acquired by liquid chromatography/ion trap time-of-flight mass spectrometry (LC/IT-TOF) systems. The deprotonation and dedeuteration energies at specific sites were calculated by the B3LYP and M06-2X density functional theory (DFT) methods with the program Gaussian 16. The [M + H]+ ion of 15-D2 -DA was 2amu larger than that of DA due to the substitution of two hydrogens with two deuteriums; however, the anion base peak of 15-D2 -DA was only 1amu larger than that of the [M-H]- ion of DA. Dedeuteration at the C15 site was proposed according to the mass spectral data. The deprotonation (dedeuteration) energies calculated by the B3LYP/6-311++G(3df,3pd)//B3LYP/6-31 + G(d) and M06-2X-D3/ma-TZVP methods showed that the C-H and C-D bonds at the C15 site have lower deprotonation (dedeuteration) energies than the energies of the hydroxy groups of DA, making their deprotonation (dedeuteration) more thermodynamically favourable. Deuteration of DA provided direct evidence of the deprotonation site of DA in the ESI source of the mass spectrometer, and the DFT method well predicted the gas-phase deprotonation site of DA.