Gas-Phase Acidities and Basicities of Alanines and N-Benzylalanines

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Cite This: J. Phys. Chem. A XXXX, XXX, XXX−XXX

Gas-Phase Acidities and Basicities of Alanines and N‑Benzylalanines by the Extended Kinetic Method Published as part of The Journal of Physical Chemistry virtual special issue “Manuel Yań ̃ez and Otilia Mó Festschrift”. Rafael Notario,*,† Juan Z. Dávalos,*,† Ramón Guzmán-Mejía,‡ and Eusebio Juaristi‡,§ †

Instituto de Química Física “Rocasolano”, CSIC, Serrano 119, 28006 Madrid, Spain Departamento de Química, Centro de Investigación y de Estudios Avanzados del IPN, Avenida IPN # 2508, 07360 Mexico City, Mexico § El Colegio Nacional, Luis González Obregón 23, Centro Histórico, 06020 Mexico City, Mexico ‡

S Supporting Information *

ABSTRACT: This paper reports an experimental determination of the gas-phase acidities and basicities of N-benzylalanines, in both their α and β forms, by means of the extended kinetic method (EKM). The experimental gas-phase acidity of β-alanine was also determined. Standard ab initio molecular orbital calculations at the G3 level were performed for alanines, and at the G3(MP2)//B3LYP level for N-benzylalanines. There is a very good agreement between the experimental and the calculated values. The more branched α-amino acids are more acidic and less basic than the linear β-amino acids.

1. INTRODUCTION Some years ago we carried out studies1,2 on the relative stability of α- versus β-amino acid isomers trying to gain an understanding why Nature has chosen α- instead of β-amino acids for the formation of compounds that are vital for the existence of life on Earth. We studied two pair of compounds, namely α-alanine and β-alanine,1 and N-benzyl-α-alanine and N-benzyl-β-alanine.2 We concluded that the more branched amino acids (α-amino acids) are intrinsically more stable than the linear ones (β-amino acids). Following in the same line of thought, we have studied now the acidity and basicity properties of the same two pairs of isomeric species representative of α- and β-amino acids studied before, α-alanine or 2-aminopropanoic acid, 1, and β-alanine or 3-aminopropanoic acid, 2, as well as N-benzyl-α-alanine or N(phenylmethyl)-α-alanine, 3, and N-benzyl-β-alanine or N(phenylmethyl)-β-alanine, 4. The schematic formulas of the four compounds are presented in Figures 1 and 2. The gas-phase acidity, GA, of an acid AH, and the basicity, GB, of a base B, are defined as the Gibbs free-energy of the following reactions:

Figure 1. Schematic formulas of α-alanine 1 and β-alanine 2.

BH+(g) → B(g) + H+(g) ΔpG 0(2) = GB, ΔpH 0(2) = PA, ΔpS 0(2)

The enthalpy and entropy changes for reaction 1 are referred to as gas-phase deprotonation enthalpy, ΔacidH 0 , and deprotonation entropy, ΔacidS0, respectively. For reaction 2 its enthalpy and entropy are referred to as proton affinity, PA, and protonation entropy, ΔpS0, respectively. Although intrinsic acidity GA and basicity GB have become available for α-alanine,3−9 there is only one experimental determination of proton affinity PA of β-alanine.9 To our

AH(g) → A−(g) + H+(g) Δacid G 0(1) = GA, Δacid H 0(1), Δacid S 0(1) © XXXX American Chemical Society

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Received: October 19, 2017 Revised: November 30, 2017 Published: December 7, 2017

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DOI: 10.1021/acs.jpca.7b10358 J. Phys. Chem. A XXXX, XXX, XXX−XXX

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The Journal of Physical Chemistry A

Figure 2. Schematic formulas of N-benzyl-α-alanine 3 and N-benzyl-β-alanine 4.

Scheme 1

software package.19 Energies of alanines were calculated using the Gaussian-3 theory, at the G3 level,20 and energies of Nbenzylalanines, due to their bigger size, were obtained at the G3(MP2)//B3LYP level.21 Alanines and N-benzylalanines present a large number of conformers of low energy due to the lack of symmetry and also the internal rotational degrees of freedom by the free rotation of different groups, NHR, COOH, or OH, regarding to the carbon skeleton. In our previous studies 1,2 on their thermochemistry we optimized the molecular structures of the lowest energy conformers of alanines and N-benzylalanines, obtaining those conformers with a significant contribution to the populated states. The optimized structures of free α-alanine, β-alanine, benzyl-α-alanine, and benzyl-β-alanine were taken from our previous papers. The optimized structures of the protonated and deprotonated forms of alanines have been obtained from G3 calculations (optimized at the MP2/631G(d) level), and for N-benzylalanines have been obtained from G3(MP2)//B3LYP calculations (optimized at the B3LYP/6-31G(d) level). The theoretical calculation of acidity GA, deprotonation enthalpy (ΔacidH0), basicity GB, and proton affinity PA was made by using eqs 1 and 2. For the thermodynamic quantities of the proton the values recently recommended by Fifen et al.22 were used. 2.3. Experimental Section. The experiments were carried out in a triple quadrupole mass spectrometer (Agilent/Varian 320) equipped with an electrospray ionization ESI source operating in the negative (acidity measurements) or positive (basicity measurements) modes. Approximately 5 × 10−5 M amino acid and the desired reference acid (or base) were mixed (in a 1:1 mass ratio), and the mixture was solved in methanol/water solution (∼1:1, vol:vol). The solutions were directly infused into the ESI source at flow rates of 10 μL/min. ESI conditions, such as needle and capillary voltages, airnebulizing temperatures, and nitrogen-drying gas temperatures were optimized to promote the formation of specific protonbound heterodimeric ions. These ions were isolated in the first quadrupole and after allowed to collision-induced dissociation (CID) experiments with argon atoms (0.2 mTorr) at various ion kinetic energies into collision chamber (second quadrupole). The dissociation product ions were analyzed with the third quadrupole. The CID experiments were performed at several collision energies, corresponding to the center of mass energies (Ecm), which were calculated as Ecm = Elab[m/(M +

knowledge, there are no previous experimental determinations of acidities or basicities for N-benzylalanines. Thus, we have experimentally determined by means of the “extended kinetic method” (EKM) the GA of β-alanine, and GA and GB of both N-benzylalanines. Briefly, the EKM is a revised and improved version of the kinetic method (KM) developed by Cooks et al. in 1977,10 which is based on the rates of competitive dissociation of massselected cluster ions formed between a sample investigated and a reference of known thermochemical properties. If the GA (or GB) of the AH (or B) molecule is of interest, one can generate a hydrogen bridged cluster ions, [A···H···Aref]− (acidity case) or [B···H···Bref]+ (basicity case), between it and a reference compound, acid ArefH (or base Bref) whose GA (or GB) is known (Scheme 1). Under appropriate conditions, the rates of dissociations can yield quantitative thermochemical information, such as GA or GB of the molecule investigated. EKM11−13 takes into account entropic effects on the competitive dissociations of [A···H··· Aref(i)]− or [B···H···Bref(i)]+ cluster ions. As a result, the EKM is one of the most frequently used experimental approaches for measuring thermochemical parameters by mass spectrometry.14−16 For comparison, we have also determined the theoretical GA and GB of alanines and N-benzylalanines at high-level ab initio calculations, G3 in the case of alanines, and because of the size of the molecules at a lower level, G3(MP2)//B3LYP, in the case of N-benzylalanines.

2. METHODS 2.1. Materials and Purity Control. Commercial samples of β-alanine [CAS: 107-95-9]a (15.0 g, 168.4 mmol, Aldrich, cat. no. 14606-4, mp 475 K, decomp.) were used. The purity of the samples was checked by NMR and C, H, and N microanalysis: NMR analysis suggested at least 99.5% purity. N-Benzyl-α-alanine (DL) [CAS 40297-69-6] and N-benzylβ-alanine [CAS 5426-62-0] were prepared following the routes described in our previous work.1 The purity of the samples was checked by DSC and C, H, and N microanalysis. Reference compounds (bases and acids) used for EKM experiments were obtained from Sigma-Aldrich and Alfa Aesar. These compounds were chosen because their GA or GB17 values similar to those calculated for the studied compounds. 2.2. Computational Details. Standard ab initio molecular orbital calculations18 were carried out using the Gaussian09 B


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The Journal of Physical Chemistry A m)], where Elab is the collision energy in the laboratory frame, m is the mass of argon and M is the mass of the heterodimeric ion. 2.4. Extended Cooks Kinetic Method (EKM). The determination of the GAs or GBs by the EKM starts with the formation of proton-bound heterodimer ions A···H···Aref(i)]− (acidity measurements) or [B···H···Bref(i)]+ (basicity measurements) generated in the ESI source from a dissolution mixture of amino acid AH (=2, 3, 4) or B (=3, 4) and the corresponding set of reference compounds (Aref(i)H or Bref(i)) with well-known intrinsic GA (GB) values. The heterodimer ions were fragmented by CID experiments to yield the corresponding monomeric ions of the sample A−(BH+) and the reference Aref(i)−(Bref(i)H+), via the two competitive dissociation channels with rate constants k and ki, respectively (Scheme 1). If secondary fragmentation is negligible, we can assume that the abundance ratio of these fragment ions is equal to the ratio k/ki. With the assumption that there are no-reverse activation barriers, the GA (GB) of the amino acids investigated is related by a linear equation which statistical procedure has been developed by Armentrout12 (Supporting Information). In the EKM, the free energy (ΔG) is replaced by its definition in terms of the enthalpy and entropy of the reactions, and it is recognized that both ΔH and ΔS can be determined by varying the Teff (effective temperature of the activated system).

Figure 4. MP2/6-31G(d)-optimized structures of β-alanine (a) and its deprotonated (b) and protonated (c) forms.

Figure 5. B3LYP/6-31G(d)-optimized structures of N-benzyl-αalanine (a) and its deprotonated (b) and protonated (c) forms.

3. RESULTS AND DISCUSSION 3.1. Molecular Structures. Amino acids come in as zwitterions when they are in crystalline state23 or in aqueous solutions. The structures are stabilized by different interactions with the environment: electrostatic, polarization and hydrogenbonding. However, in the gas phase amino acids exist as nonionized forms, because the intermolecular interactions have no effect and they are flexible systems. Alanines and N-benzylalanines present a large number of conformers in the gas phase, in which the intramolecular hydrogen bonds become important. The energy barriers separating the different conformers are rather small, and therefore, it is not generally possible to isolate a specific conformer at room temperature.24 The most stable conformers of alanines and N-benzylalanines, and their protonated and deprotonated forms, are stabilized by hydrogen bonds. Protonation occurs in the amino group and deprotonation in the COOH group. The most stable conformer of free α-alanine (Figure 3) presents a bifurcated NH···OC hydrogen bond, between the oxygen of the carboxylic group and the two hydrogen atoms of the amino group, but the bifurcated H···O interactions are not equal (2.61 and 2.83 Å) due to the chirality of the α-carbon atom. In the protonated and deprotonated forms there is only one hydrogen bond that is

Figure 6. B3LYP/6-31G(d)-optimized structures of N-benzyl-βalanine (a) and its deprotonated (b) and protonated (c) forms.

stronger than in the free molecule (2.08 and 2.09 Å, respectively). The intramolecular hydrogen bond leads to the formation of a five-membered ring motif. The most stable conformer of free β-alanine (Figure 4) is stabilized by one NH···OC hydrogen bond. The hydrogen bond is now formed between the oxygen atom of the carboxylic group and only one of the hydrogens of the amino group, presumably because a bifurcated interaction imposes too close a distance between the atoms involved. Because of the additional methylene group, the hydrogen bond leads to the formation of a six-membered ring motif, with a much shorter H···O distance of 2.35 Å. This distance become shorter in the protonated and deprotonated forms (1.82 and 2.03 Å, respectively). The most stable conformers of free N-benzyl-α-alanine and N-benzyl-β-alanine are shown in Figures 5 and 6. They are stabilized by NH···OC hydrogen bonds (2.54 and 2.29 Å, for N-benzyl-α-alanine and N-benzyl-β-alanine, respectively). The hydrogen bonds are formed between the O atom of the CO group and the H atom of the NH group. There is another hydrogen bond, with a length of 2.77 Å, in the

Figure 3. MP2/6-31G(d)-optimized structures of α-alanine (a) and its deprotonated (b) and protonated (c) forms. C


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Figure 7. Thermokinetic plots: first (left) and second (right) sets for amino acids AH = 2, 3, 4.

data points gives a straight line with a slope of (ΔacidH0 − 0 ΔacidHavg ref ) and an intercept of −Δ(ΔS )/R (Tables S2 and S3,Supporting Information). As suggested by Armentrout,12 the uncertainties of the first thermo-kinetic plot were included in the second one. Our experimentally measured ΔacidH0(2) = 1435.1 ± 8.8 kJ·mol−1, ΔacidS0(2) = 93.3 ± 8.4 J·mol−1·K−1, and GA (2) = 1407.3 ± 8.8 kJ·mol−1 for β-alanine were thus avg obtained from the ΔacidHavg ref , ΔacidSref , and their uncertainties and are shown as the experimental values in Table 2. Four compounds with GAs ranging from 1382.0 to 1398.3 kJ·mol−1 (methyl-4-hydroxybenzoate, 2,4,6-trimethylbenzoic acid, benzoic acid, and 3,4,5-trimethylbenzoic acid) were chosen as references for GA measuring of N-benzyl-α-alanine (3), and five compounds with GAs ranging from 1382.0 to 1398.3 kJ·mol−1 (methyl-4-hydroxybenzoate, 2,6-dimethylbenzoic acid, o-anisic acid, 2,4,5-trimethylbenzoic acid, and 3,4,5trimethylbenzoic acid), for N-benzyl-β-alanine (4). The results were analyzed in the same manner as for β-alanine (2) and are shown in Figure 7. The final derived thermochemical results (Table 2) are summarized as ΔacidH0(3) = 1413.5 ± 9.2 kJ· mol−1, ΔacidS0(3)= 91.5 ± 8.4 J·mol−1·K−1, and GA (3) = 1386.2 ± 9.2 kJ·mol−1 for N-benzyl-α-alanine and ΔacidH0(4) = 1415.7 ± 9.2 kJ·mol−1, ΔacidS0(4)= 83.1 ± 8.4 J·mol−1·K−1, and GA (4) = 1390.9 ± 9.2 kJ·mol−1 for N-benzyl-β-alanine. 3.2.2. Basicity (Protonation) of B = 3 and 4. For N-benzylα-alanine (3), the following five compounds were taken as references: cyclohexylamine, tert-amylamine, diallylamine, 3aminopyridine, and 4-tert-butylpyridine (GBs ranging from

structure of N-benzyl-α-alanine, formed between the O atom of the CO group and one of the H atoms of the CH2 group. These hydrogen bonds are in the protonated and deprotonated structures, the NH···OC being stronger than in free amino acid (2.09 Å in protonated and deprotonated N-benzyl-αaniline, 1.90 Å in deprotonated N-benzyl-β-aniline, and 1.85 Å in protonated N-benzyl-β-aniline). The deprotonated form of N-benzyl-β-aniline is extra-stabilized by a hydrogen bond formed between the O atom of the CO group and the H atom of one of the CH groups of the benzene ring (2.19 Å). 3.2. EKM Analysis. 3.2.1. Acidity (Deprotonation) of AH = 2, 3, and 4. For β-alanine (2), four compounds with GAs ranging from 1399.5 to 1422.1 kJ·mol−1 (Table S1 in the Supporting Information) were chosen as references: phenyl acetic acid, 3-chlorophenol, trimethyl acetic acid, and 4fluorophenol. The natural logarithm of [A−]/[A−ref(i)] measured at 13 collision energies (Ecm, from 0.75 to 3.75 eV) are plotted 0 avg against the values of (Δ acid H ref(i) − Δ acid H ref ) (first thermokinetic plot depicted in Figure 7) where ΔacidHavg ref , the average of set deprotonation enthalpies of reference acids is 1437.8 ± 8.8 kJ·mol−1. Linear regression with a least-squares fit of the data points at each collision energy Ecm yields a straight line with the slope 1/RTeff and the Y-intercept of −[(ΔacidH0 − 0 ΔacidHavg ref )/RTeff − Δ(ΔS )/R]. The deprotonation enthalpy 0 ΔacidH of 2 was obtained from the second set of thermokinetic plots. The values of the negative Y-intercepts obtained in the first plot were plotted against its corresponding slopes (Figure 7). The linear regression with a least-squares fit of the D


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Figure 8. Thermokinetic plots: first (left) and second (right) sets for amino acids B = 3, 4.

899.6 to 925.9 kJ·mol−1, Supporting Information). The natural logarithms of [BH+]/[Bref(i)H+] measured at seven collision energies (Ecm, from 1.25 to 3.75 eV) are plotted against the values of (PAref(i) − PAavg ref ) (first set of thermokinetic plots, presented in Figure 8) where PAavg ref , the average of set proton

Table 2. Comparison of Experimental and Calculated GasPhase Acidities and Basicities of the Studied α- and βAmino Acids GA/kJ·mol−1 experimental

Table 1. Calculated Enthalpies at 298 K, H298, and Gibbs Free Energies at 298 K, G298, for All the Studied Species (All Values in hartrees)

α-alanine β-alanine N-benzyl-αalanine N-benzyl-βalanine

G3 H298 neutral protonated deprotonated neutral protonated deprotonated

α-Alanine −323.517445 −323.556306 −323.858940 −323.898243 −322.974720 −323.013221 β-Alanine −323.515730 −323.554293 −323.867427 −323.905483 −322.971984 −323.010068 G3(MP2)//B3LYP H298

neutral protonated deprotonated neutral protonated deprotonated

G298

N-Benzyl-α-alanine −593.186418 −593.546182 −592.647340 N-Benzyl-β-alanine −593.184179 −593.551957 −592.646389

± ± ± ±

ΔacidH0/kJ·mol−1

calculated

a

8.4 8.4b 8.8c 9.2c

1399.6

1390.9 ± 9.2c

1401.0 1396.0 1407.3 1386.2

β-alanine N-benzyl-αalanine N-benzyl-βalanine

G298

± ± ± ±

a

calculated

7.9 8.8b 8.8c 9.2c

1431.1

1402.6 1390.3

1430.0 1425.0 1435.1 1413.5

1391.8

1415.7 ± 9.2c

1418.2

GB/kJ·mol−1 α-alanine

experimental

1433.8 1421.5

PA/kJ·mol−1

experimental

calculated

experimental

calculated

867.7d 865.4 ± 0.4e 864.0 ± 6.3f 863.6 ± 6.7g

871.5

901.6d 902 ± 4h 894.5 ± 0.4e

902.8

c

915.7 ± 8.4

895.8 918.4

927 ± 4h 954.0 ± 8.4c

929.6 950.8

934.3 ± 8.4c

938.5

973.3 ± 8.4c

971.8

a

Taken from ref 3. bTaken from ref 4. cThis work. dTaken from ref 5. Taken from ref 6. fTaken from ref 7. gTaken from ref 8. hTaken from ref 9.

−593.241365 −593.601160 −592.701822

e

−593.239000 −593.606470 −592.698872

derived results, shown as experimental values in Table 2 are PA(3) = 954.0 ± 8.4 kJ·mol−1, ΔpS0(3) = 128.4 ± 8.4 J·mol−1· K−1, and GB(3) = 915.7 ± 8.4 kJ·mol−1. The reported uncertainties were obtained with the same considerations as for the acidity case. Five compounds with GBs ranging from 925.9 to 947.7 kJ· mol−1 (4-tert-butylpyridine, dipropylamine, dibutylamine, diisopropylamine, and 4-aminopyridine) were chosen as references for GB measuring of N-benzyl-β-alanine (4). The results were analyzed in the same manner as for N-benzyl-αalanine (3) and are depicted in Figure 8. The derived thermochemical results, reported as experimental values in

affinities of reference bases, is equal to 946.7 ± 8.4 kJ·mol−1. The proton affinity PA of 3 was determined from the second set of thermokinetic plots. The Y-intercept values, as obtained from the first set of thermokinetic plots, were plotted against the corresponding negative slopes, 1/RTeff (Figure 8). The linear regression with a least-squares fit of the data points gives a straight line with a slope of (PA − PAavg ref ) and an intercept of −Δ(ΔS0)/R (Supporting Information). The thermochemical E


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Figure 10. Comparison of experimental gas-phase proton affinities (PAs) of different isomeric pairs, in linear and branched forms. All values are in kJ·mol−1. In parentheses the difference of proton affinity between the linear and the branched form is given. From top to bottom: α-alanine/β-alanine; isopropylamine/n-propylamine; isobutanol/1-butanol; N-benzyl-α-alanine/N-benzyl-β-alanine.

alanines (taken for the experimental value for α-alanine the mean of the two values available in the literature, collected in Table 2), and 4.7 kJ·mol−1 in the case of N-benzylalanines. The difference of acidity between the linear and the branched forms is comparable to that observed in other isomeric pairs17 related to the amino acids studied, as shown in Figure 9, ranging between 2 kJ·mol−1 for the pair butyric/isobutyric acid and 10 kJ·mol−1 for the pair butane/isobutane. The more acidic compound is N-benzyl-α-alanine, with a GA value (1386.2 kJ·mol−1) comparable to that of fluoroacetic acid (1386.0 kJ·mol−1),17 and it is more acidic than benzoic acid (1393.0 kJ·mol−1).17 In the case of basicity (or proton affinity), the linear β-amino acids are clearly more basic than the α-amino acids, the difference in PA being 25 kJ·mol−1 in the case of alanines, and 19.3 kJ·mol−1 in the case of N-benzylalanines. However, the difference of proton affinity between the linear and the branched forms is not comparable to that observed in other isomeric pairs17 related to the amino acids studied, as shown in Figure 8, because in the cases where experimental values are available in the literature, the pairs n-propylamine/isopropylamine or 1-butanol/isobutanol, the branched form is more basic than the linear form, 6 and 4.5 kJ·mol−1, respectively (Figure 10). The more basic compound is N-benzyl-β-alanine, with a GB value (934.3 kJ·mol−1) comparable to those of N-methylpyrrolidine (934.8 kJ·mol−1)5 or 1,4,4-trimethylpiperidine (934.7 kJ·mol−1).5

Figure 9. Comparison of experimental gas-phase acidities (GAs) of different isomeric pairs, in linear and branched forms. All values are in kJ·mol−1. In parentheses the difference of acidity between the linear and the branched form is given. From top to bottom: α-alanine/βalanine; isopropylamine/n-propylamine; isobutyric acid/n-butyric acid; isobutane/n-butane; isobutanol/1-butanol; N-benzyl-α-alanine/ N-benzyl-β-alanine.

Table 2, are PA(4) = 973.3 ± 8.4 kJ·mol−1, ΔpS0(4) = 130.6 ± 8.4 J·mol−1·K−1, and GB(4) = 934.3 ± 8.4 kJ·mol−1. 3.3. Theoretical Values. Calculated enthalpies and Gibbs free energies at 298 K, for all the amino acids studied, and their protonated and deprotonated structures, are given in Table 1. All of the structures are minima on the potential energy surface. Gas-phase acidities and basicities have been calculated using eqs 1 and 2. Calculated GA, ΔacidH0, GB, and PA values are collected in Table 2 together with the experimental values. As can be seen, the agreement between calculated and experimental values is very good. 3.4. Comparison of Acidities and Basicities of α- and β-Amino Acids. The experimental order of acidity is β-alanine < α-alanine < N-benzyl-β-alanine < N-benzyl-α-alanine, whereas the order of basicity is α-alanine < β-alanine < Nbenzyl-α-alanine < N-benzyl-β-alanine (Table 2). The more branched α-amino acids are slightly more acidic than the counterpart linear β-amino acids, 8.8 kJ·mol−1 in the case of

4. CONCLUSIONS We have carried out the experimental determination of the gasphase acidities and basicities of N-benzylalanines, in both their α and β forms, by means of the extended kinetic method (EKM). The experimental gas-phase acidity of β-alanine was F


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(8) Wu, J.; Lebrilla, C. B. Basicity of Oligomeric Peptides that Contain Glycine, Alanine, and Valine − The effects of the Alkyl Side Chain on Proton Transfer Reactions. J. Am. Soc. Mass Spectrom. 1995, 6, 91−101. (9) Hahn, I.-S.; Wesdemiotis, C. Protonation Thermochemistry of β-alanine. An Evaluation of Proton Affinities and Entropies Determined by the Extended Kinetic Method. Int. J. Mass Spectrom. 2003, 222, 465−479. (10) Cooks, R. G.; Kruger, T. L. Intrinsic Basicity Determination Using Metastable Ions. J. Am. Chem. Soc. 1977, 99, 1279−1281. (11) Cheng, X. H.; Wu, Z. C.; Fenselau, C. Collision Energy Dependence of Proton-Bound Dimer Dissociation: Entropy Effects, Proton Affinities, and Intramolecular Hydrogen-Bonding in Protonated Peptides. J. Am. Chem. Soc. 1993, 115, 4844−4848. (12) Armentrout, P. B. Entropy Measurements and the Kinetic Method: A Statistically Meaningful Approach. J. Am. Soc. Mass Spectrom. 2000, 11, 371−379. (13) Ervin, K. M. Microcanonical Analysis of the Kinetic Method. The Meaning of the “Apparent Entropy. J. Am. Soc. Mass Spectrom. 2002, 13, 435−452. (14) Bouchoux, G. Gas-Phase Basicities of Polyfunctional Molecules. Part 1: Theory and methods. Mass Spectrom. Rev. 2007, 26, 775−835. (15) Guerrero, A.; Baer, T.; Chana, A.; González, J.; Dávalos, J. Z. Gas Phase Acidity Measurement of Local Acidic Groups in Multifunctional Species: Controlling the Binding Sites in Hydroxycinnamic Acids. J. Am. Chem. Soc. 2013, 135, 9681−9690. (16) Dávalos, J. Z.; Lima, C. F. R. A. C.; Silva, A. M. S.; Santos, L. M. N. B. F.; Erra-Balsells, R.; Salum, M. L. Energetics of Neutral and Deprotonated (Z)-Cinnamic Acid. J. Chem. Thermodyn. 2016, 95, 195−201. (17) Linstrom, P. J., Mallard, P. G., Eds. NIST Chemistry Webbook, NIST Standard Reference Database Number 69; National Institute of Standards and Technology: Gaithersburg MD, DOI 10.18434/ T4D303. (18) Hehre, W. J.; Radom, L.; Schleyer, P. v. R.; Pople, J. A. Ab Initio Molecular Orbital Theory; Wiley: New York, 1986. (19) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; et al. Gaussian09; Gaussian, Inc.: Wallingford, CT, 2013. (20) Curtiss, L. A.; Raghavachari, K.; Redfern, P. C.; Rassolov, V.; Pople, J. A. Gaussian-3 (G3) Theory for Molecules Containing First and Second-Row Atoms. J. Chem. Phys. 1998, 109, 7764−7776. (21) Baboul, A.; Curtiss, L. A.; Redfern, P. C.; Raghavachari, K. Gaussian-3 Theory Using Density Functional Geometries and ZeroPoint Energies. J. Chem. Phys. 1999, 110, 7650−7657. (22) Fifen, J. J.; Dhaouadi, Z.; Nsangou, M. Revision of the Thermodynamics of the Proton in the Gas Phase. J. Phys. Chem. A 2014, 118, 11090−11097. (23) Allen, F. H. The Cambridge Structural Database: A Quarter of a Million Crystal Structures and Rising. Acta Crystallogr., Sect. B: Struct. Sci. 2002, 58, 380−388. (24) Kaur, D.; Sharma, P.; Bharatam, P. V.; Kaur, M. Understanding Selenocysteine through Conformational Analysis, Proton Affinities, Acidities and Bond Dissociation Energies. Int. J. Quantum Chem. 2008, 108, 983−991.

also determined. There is a very good agreement between the experimental and the calculated values. The more branched α-amino acids are slightly more acidic than the counterpart linear β-amino acids, but the linear βamino acids are clearly more basic than the α-amino acids. The behavior in acidity is similar to that observed in other isomeric pairs related to the amino acids studied; however, the behavior in basicity is opposite to the observed, where the branched forms are more basic than the linear forms.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jpca.7b10358. Details of the experimental determination of the acidity and basicity of the studied amino acids, including tables of gas-phase thermochemical quantities and experimental conditions, values and plots of ln([A−]/[Aref(i)−]) and ln([BH+]/[Bref(i)H+]) of CID products, and plots of Teff vs CID; Cartesian coordinates of α- and β-alanines and N-benzylalanines, in their neutral, protonated, and deprotonated forms (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*R. Notario. E-mail: [email protected]. *J. Z. Dávalos. E-mail: [email protected]. ORCID

Rafael Notario: 0000-0003-2957-8183 Notes

The authors declare no competing financial interest.

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ADDITIONAL NOTE CAS Registry Numbers are provided by the authors.

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REFERENCES

(1) Ribeiro da Silva, M. A. V.; Ribeiro da Silva, M. D. M. C.; Santos, A. F. L. O. M.; Roux, M. V.; Foces-Foces, C.; Notario, R.; GuzmánMejía, R.; Juaristi, E. Experimental and Computational Thermochemical Study of α-Alanine (DL) and β-Alanine. J. Phys. Chem. B 2010, 114, 16471−16480. (2) Notario, R.; Roux, M. V.; Foces-Foces, C.; Ribeiro da Silva, M. A. V.; Ribeiro da Silva, M. D. M. C.; Santos, A. F. L. O. M.; GuzmánMejía, R.; Juaristi, E. Experimental and Computational Thermochemical Study of N-Benzylalanines. J. Phys. Chem. B 2011, 115, 9401− 9409. (3) Jones, C. M.; Bernier, M.; Carson, E.; Colyer, K. E.; Metz, R.; Pawlow, A.; Wischow, E. D.; Webb, I.; Andriole, E. J.; Poutsma, J. C. Gas-phase Acidities of the 20 Protein Amino Acids. Int. J. Mass Spectrom. 2007, 267, 54−62. (4) Locke, M. J.; McIver, R. T., Jr Effect of Solvation on the Acid/ Base Properties of Glycine. J. Am. Chem. Soc. 1983, 105, 4226−4232. (5) Hunter, E. P.; Lias, S. G. Evaluated Gas Phase Basicities and Proton Affinities of Molecules: An Update. J. Phys. Chem. Ref. Data 1998, 27, 413−656. (6) Bouchoux, G.; Salpin, J. Y. Gas-phase Basicity of Glycine, Alanine, Proline, Serine, Lysine, Histidine and Some of Their Peptides by the Thermokinetic Method. Eur. Mass Spectrom. 2003, 9, 391− 402. (7) Cassady, C. J.; Carr, S. R.; Zhang, K.; Chung-Phillips, C. Experimental and Ab Initio Studies of Protonation of Alanine and Small Peptides of Alanine and Glycine. J. Org. Chem. 1995, 60, 1704− 1712. G


Gas-Phase Acidities and Basicities of Alanines and N-Benzylalanines

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