Photoelectron Spectra of Some Antibiotic Building Blocks: 2

Jul 17, 2012 - eChemistry Laboratory, Faculty of Life and Social Sciences, Swinburne University of Technology, Melbourne, Victoria 3122, Australia...
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Photoelectron Spectra of Some Antibiotic Building Blocks: 2‑Azetidinone and Thiazolidine-Carboxylic Acid Marawan Ahmed,† Aravindhan Ganesan,† Feng Wang,† Vitaliy Feyer,‡,∥ Oksana Plekan,‡,⊥ and Kevin C. Prince*,‡,§ †

eChemistry Laboratory, Faculty of Life and Social Sciences, Swinburne University of Technology, Melbourne, Victoria 3122, Australia Sincrotrone Trieste, Area Science Park, I-34149 Basovizza, Trieste, Italy § Istituto Officina dei Materiali, Consiglio Nazionale delle Ricerche, Area Science Park, I-34149 Trieste, Italy ‡

S Supporting Information *

ABSTRACT: X-ray photoelectron spectra of the core and valence levels of the fundamental building blocks of β-lactam antibiotics have been investigated and compared with theoretical calculations. The spectra of the compounds 2-azetidinone and the 2- and 4-isomers of thiazolidine-carboxylic acid are interpreted in the light of theoretical calculations. The spectra of the two isomers of thiazolidine-carboxylic acid are rather similar, as expected, but show clear effects due to isomerization. Both isomers are analogues of proline, which is well-known to populate several low energy conformers in the gas phase. We have investigated the low energy conformers of thiazolidine-4-carboxylic acid theoretically in more detail and find some spectroscopic evidence that multiple conformers may be present. The measured valence levels are assigned for all three compounds, and the character of the frontier orbitals is identified and analyzed.

1. INTRODUCTION The antibiotic penicillin was discovered nearly a century ago and, like many other antibiotics, belongs to the β-lactam class,1 as they are based on β-lactam, systematic name 2-azetidinone,2 and this motif is present not only in penicillins but also in a number of other antibiotics, such as cephalosporins, carbapenems, and monobactams. The distinctive feature of penicillins is a thiazolidine-4-carboxylic acid moiety fused to the azetidinone ring. In the present work, we probe the chemical nature of 2azetidinone (AZ2), thiazolidine-4-carboxylic acid (TZ4), and its isomer thiazolidine-2-carboxylic acid (TZ2), Figure 1. Both TZ4 and TZ2 are analogues of the important amino acid proline,3−6 and they differ from one another only by the positions of the sulfur atoms in the pyrrolidine ring. The structure3,4 and photoemission spectra5,6 of proline have been reported previously, and in the gas phase, proline exists as four main conformers associated with two different kinds of internal hydrogen bonds and two kinds of ring puckering. The two types of hydrogen bonds result in two peaks in the N 1s core ionization binding energy spectrum of proline.7 We wished to know if these two analogues of proline also display the same kind of conformational behavior. For reasons that will become clear below, we investigated in detail the conformational landscape of TZ4. Another primary motive for comparing the two isomers was to provide a cross-check of our results for TZ4 and TZ2: spectra of isomers should be similar but with foreseeable differences. Electronic structural studies of these important building blocks of antibiotics are rare and incomplete. There appears to be only one study available of the core ionization of 2azetidinone,8 which is incomplete, and there appear to be no photoelectron data for the present isomers of thiazolidine 2012

carboxylic acid. The structure of AZ2 has been determined by microwave spectroscopy as well as X-ray crystallography9−11 and studied by theoretical calculations12 and infrared spectroscopy:13,14 the molecule is planar, with Cs symmetry. Thiazolidine4-carboxylic acid has been studied by X-ray crystallography,15 and like proline, it is zwitterionic in the solid state. It forms a single intramolecular hydrogen bond NH···O in the solid state, as well as intermolecular hydrogen bonds. Most recently, the conformational landscapes of protonated TZ4 derivatives have been explored.16 All natural amino acids are zwitterionic in the solid state and neutral in the gas phase, so we expect TZ2 and TZ4 also to be neutral in the gas phase. One goal of this work was to investigate whether the amino-oxygen hydrogen bond is conserved in the gas phase or whether other conformations are adopted. We are not aware of any available structural data for TZ2. Its derivatives, however, have applications in aroma and pharmaceutical chemistry.17,18

2. EXPERIMENTAL AND COMPUTATIONAL DETAILS The measurements were performed at the gas phase photoemission beamline of Elettra, Trieste, Italy, using apparatus and calibration methods described previously.5−7,19 The total resolution of the photons and analyzer was estimated to be 0.2, 0.32, 0.46, and 0.78 eV at photon energies of 100 (valence band), 382 (C 1s), 495 (N 1s), and 628 eV (O 1s), respectively. The compounds were supplied by Sigma Aldrich and used without further purification. The samples were Received: March 28, 2012 Revised: June 26, 2012 Published: July 17, 2012 dx.doi.org/10.1021/jp302950y | J. Phys. Chem. A 2012, 1 6166, 

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Figure 1. (a) 2-Azetidinone, (b) thiazolidine-2-carboxylic acid, and (c) thiazolidine-4-carboxylic acid. Upper figures: schematic structures with atomic numbering and Hirshfeld charges in parentheses. Lower figures: 3-dimensional ball and stick models of the ground state structures. Colors represent red, oxygen; blue, nitrogen; dark gray, carbon; light gray, hydrogen. In the pdf version of this article, the reader can click on the figure and then rotate, enlarge, or reduce the image, using Acrobat 8.1 and above.

evaporated from a noninductively wound furnace at temperatures of AZ2, 298 K (room temperature); TZ2 and TZ4, 406 K. They were checked for evidence of thermal decomposition, such as spectral changes as a function of time, presence of decomposition products in valence spectra (H2O, CO2, etc.), discoloration after heating, etc. No evidence was found for decomposition of the compound. The spectra at the carbon, nitrogen, and oxygen K-edges were normalized to the photon flux measured by a photodiode. All geometry optimizations were performed using the density functional theory (DFT) based B3LYP/6-311++G** model, which is incorporated in the latest version of the Gaussian09 (G09)20 computational chemistry package. The B3LYP model has proven to provide reliable geometries for several biomolecules.21−23 The outer valence Green’s function (OVGF)24 theory, which is coupled with the 6-311++G** basis set was used to calculate valence spectra. The OVGF model, which is incorporated in the G09 computational chemistry package, accurately predicts outer valence ionization energies.25−28 The calculations of the binding energy (ionization potential) spectra of AZ2 were carried out using the Amsterdam Density Functional (ADF) computational chemistry program 29−31 except for the OVGF calculations. The ΔEKS method takes the energy difference in the total Kohn−Sham energies between the core-ionized cation and the neutral parent molecule using the (PW86-PW91)/et-pVQZ model,32 thereby considering the core hole relaxation effects. The vertical ionization energies and Hirshfeld charges of TZ2, TZ4, and AZ2 were calculated using the LB94/et-pVQZ33 model for the core shell, and the vertical valence ionization spectra were calculated using the SAOP/et-pVQZ model.34 Here, the basis set et-pVQZ is an even-tempered, polarized-valence quadrupleζ Slater-type basis set.35 The 6-311++G** basis set, which is almost the largest computationally feasible basis set for the size of molecules in this study, has proven to produce reliable

properties such as geometries and outer valence IPs when combined with the B3LYP and the OVGF models, respectively. It is important to produce geometries of the molecules as accurately as possible and precise IPs of the electrons in the frontier orbitals. However, neither the B3LYP/6-311++G** model nor the OVGF/6-311++G** model is able to produce the desired accuracy for the core IPs and the complete valence IPs (not just for outer valence), which are presented in the experimental data. As a result, different models, such as (PW86PW91)/et-pVQZ, LB94/et-pVQZ and SAOP/et-pVQZ, have different precisions and are selected for the required accuracy and therefore are employed for the IP calculations. The meta-Koopman’s theorem36 was applied without any further modifications and scaling. The sulfur atom is treated in the ZORA/TZ2P approximation to account for relativistic effects.37 The calculation is of the restricted type, and spin orbit effects are not included. Several other software packages including Gaussview 5.0,38 ADFVIEW,29−31 Molden,39 and a recently developed 3D-pdf technique26,27 were employed in the present study for visualization.

3. RESULTS AND DISCUSSION 3.1. Core Level Spectra. The calculated structure of AZ2 is in agreement with previous structural determinations and other available calculations,9,12,13 and the structural parameters are given in the Supporting Information (S1). The optimized structure and atomic numbering are shown in Figure 1, with Hirshfeld charges on each atom shown in parentheses. The calculated structures of TZ2 and TZ4 were also in agreement with solid-state crystallographic data; 15 the results are presented in the Supporting Information (S2). These molecules are more flexible than AZ2 and can therefore exist in the gas phase as conformers with populations determined by their relative free energies, like the amino acid proline of which dx.doi.org/10.1021/jp302950y | J. Phys. Chem. A 2012, 1 6166, 

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Figure 2. Conformers of TZ4. Colors are the same as those in Figure 1. Conformer I, OH···N; conformer II, CH···O; conformer III, OH···S; and conformer IV, NH···OC.

they are analogues. The ground states of TZ2 and TZ4 are shown in Figure 1b,c, and the four lowest energy conformers of TZ4 are shown in Figure 2. For TZ4, we calculated the electronic energy and core photoelectron spectra of the four most stable conformers with the hydrogen bonding indicated in Figure 2, namely, the ground state (OH···N) conformer I; conformer II (CH···N); conformer III (OH···S); and conformer IV (NH···OC). The reasons for choosing the conformers of this isomer for detailed study are explained below. The relative electronic energies (zero K) are 0, 34.7, 21, and 36 kJ·mol−1, respectively. Atomic charges are important quantitative properties for characterizing the behavior of atoms in molecules. The Hirshfeld scheme evaluates a point-charge localized on the kth atom in a molecule.40,41 Partitioning of electron density according to the Hirshfeld scheme40 has been widely applied in atomic charge analyses and to interpret experimental X-ray diffraction data.42,43 The Hirshfeld charge can predict site selectivity in a way that agrees well with experiment in most cases,41 such as reactive sites, and is superior to other more familiar schemes, such as the Mulliken and natural population analyses.44 It is also found27,45 that the atomic site based Hirshfeld charges calculated using the wave functions produced using the same model (i.e., LB94/ et-PVQZ) for the core IPs provide a convincing interpretation for the core binding energy spectra of molecules, in the case that core level shifts are dominated by initial state effects. The Mulliken scheme is better known for historical reasons, but we feel the Hirshfeld approach is more precise. In Figure 1, the atomic based Hirshfeld charges calculated using the LB94/et-pVQZ model are presented in parentheses for the optimized structures of AZ2, TZ2, and TZ4. For AZ2, all non-hydrogen atoms, that is, O, N, C(3), and C(4) possess negative charges except for C(2), which is bound to the O atom through the carbonyl CO bond. The Hirshfeld charge on C(2) is positive, 0.167, in agreement with a previous study of Gil and co-workers.46 This may imply that the positively charged carbonyl carbon site may be subject to major nucleophilic attack.47 The order of Hirshfeld charges of the carbon atoms is given by C(2) > C(4) > C(3), which in a first approximation (considering only initial state effects) may be an indicator of the order of their core ionization energies. Similarly, for TZ4, the order of Hirshfeld charges is C(6) > C(4) > C(2) > C(5), again providing a prediction of the order of core level binding energies for the case of spectra determined primarily by initial state effects. For TZ2, the order is C(6) > C(2) > C(4) > C(5). In this case, C(6) and C(2) both have positive charges, due to the proximity of electronegative neighbors (two oxygen atoms or N.) Figure 3a shows the C 1s spectrum of AZ2 compared with our theoretically calculated spectrum, and Table 1 summarizes

Figure 3. Core level spectra of azetidinone. (a) C 1s, experimental, upper curve; theoretical (ΔEKS), lower curve, broadened to match approximately the experimental spectrum. (b) Experimental O 1s and N 1s (inset) spectra.

Table 1. Experimental and Simulated Inner Core Shell Ionization Potentials (eV) of AZ2 Using the LB94/et-pVQZ Level of Theory atomic site

verticala

ΔEKSb

exptl

literaturec

C(2)O C(3)−N C(4)−C N O

292.40 290.28 291.28 404.10 534.14

293.60 291.26 292.35 405.97 537.31

293.94 291.19 292.23 405.84 537.48

291.80

405.76 537.32

a

Vertical IPs using the LB94/et-PVQZ model applying the metaKoopman’s theorem. bΔEKS(PW86-PW91). cSee ref 8.

the data. The theoretical spectrum is contracted on the energy scale by about 20% compared with the experimental result, and the assignment is consistent with what is expected from the basic chemical arguments based on the initial state charge transfer described above. One also expects that the binding energy increases with the number of electronegative nearest neighbors as quantified in the Hirshfeld charges, namely, C(2) > C(4) > C(3), and this is observed. This suggests that the core level energies are mostly determined by initial rather than final state effects. A notable feature of the experimental spectrum is that the peak due to C(2), bonded to oxygen, is fairly symmetric, whereas the other two peaks are skewed strongly to higher binding energy. These broad and asymmetric Franck−Condon envelopes indicate that the equilibrium geometries in the ground and ionic states are very different for ionization of C(4) and C(3) but are more similar for ionization of C(2). The origin of this effect may be in part due to the strain in the ring for the ground state structure. The N 1s and O 1s spectra of AZ2 are shown in Figure 3b; the calculated and experimental energies are summarized in Table 1. The N 1s peak is slightly asymmetric and has a measured full width at half-maximum (fwhm) of 0.75 eV. The O 1s spectrum shows a single main peak, as expected, with a fwhm of 0.93 eV. A satellite is visible at 6.5 eV from the main dx.doi.org/10.1021/jp302950y | J. Phys. Chem. A 2012, 1 6166, 

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Table 2. Experimental and Simulated Inner Core Shell Ionization Potentials (eV) of the Most Stable Conformer of TZ2 in the Gas Phase, Using the LB94/et-pVQZ Level of Theorya TZ2 core level

theory

C(2) 1s C(4) 1s C(5) 1s C(6) 1s N(3) 1s O(7) 1s O(8) 1s O(7) − O(8) difference S, 1s S, 2s S, 2p S, 2p

291.97 291.40 290.89 293.19 404.25 534.50 536.09 1.59 2443.49 223.79 169.90

exptl 292.09 291.55 291.07 295.04 405.21 538.31 540.11 1.79

2p3/2, 169.17 2p1/2, 170.40

a

The theoretical value of the S 2p binding energy is the average of three molecular field split components. The theory does not include spin−orbit coupling effects.

Table 3. Experimental and Simulated Core Ionization Potentials of TZ4 Conformers Applying the LB94/et-pVQZ Modela orbital

I

II

III

IV

exptl

C(2) C(4) C(5) C(6) N(3) O(7) O(8) ΔE (kJ·mol−1)

291.63 291.83 290.78 293.39 404.26 534.72 536.23 0.0

291.09 291.85 290.92 293.57 403.71 534.92 536.62 34.7

291.66 291.72 291.16 293.34 404.04 534.63 536.12 21.0

291.14 291.75 291.04 293.57 403.46 534.97 536.68 36.0

291.89 292.13 291.29 295.21/294.78 405.32 538.44 540.19

a

The relative electronic energies (zero K) are shown in the lowest row.

peak, which we assign to a π−π* excitation of the carbonyl π bond on core ionization. Tables 2 and 3 summarize the binding energies of TZ2 and TZ4, and Figure 4a shows the S 2p spectra of these two compounds; they show only a very small shift, comparable with the measurement accuracy of the experiment, with TZ4 being at slightly lower binding energy. The TZ4 spectra are also slightly broader. The N 1s spectra are also very similar, Figure 4c, with the TZ4 binding energy slightly higher, and as for the S 2p spectra, the peak is slightly broader, with the extra width appearing on the high binding energy side.

The O 1s spectra of the carboxylic acid group, Figure 4d, show two peaks with slightly higher binding energy for TZ4, like N 1s but in contrast to S 2p. The splitting of the carbonyl and hydroxyl O 1s peak also differs, with TZ4 having a slightly smaller splitting. Theory correctly predicts this difference qualitatively. The C 1s spectra present a more severe challenge to theory as the spectra are richer, with four atoms in each molecule. The spectra in Figure 4b show four distinct features, labeled A to D, and a shoulder labeled D′, which is more pronounced for TZ4 than for TZ2. The theory qualitatively predicts the trend that the peaks A, B, and C are roughly equally spaced for TZ2, while peaks B and C are closer together for TZ4. However, the relative energy of peak D, due to the carboxylic carbon atom C(6), is underestimated by nearly a factor of 2. For both compounds, the highest binding energy peak D is due to the carboxylic acid carbon C(6), as expected from basic electronegativity arguments. The second highest binding energy peak C is predicted to be due to C(2) for TZ2 and C(4) for TZ4. This is due to the electron withdrawing nature of the carboxylic acid group. Peak A is assigned to C(5) for both compounds: it is bonded to C and S only and thus the core level is not expected to undergo significant shifts on isomerization. The ordering in this assignment is consistent with the order of the Hirshfeld charges displayed in Figure 1, again indicating that the core level shifts are largely determined by initial state effects. A notable feature in the C 1s spectra is the shoulder D′ on the highest binding energy feature. This is most pronounced for TZ4, which also shows a slight broadening of the S and N core levels compared with TZ2. It is known that the presence of conformers can cause peak shape changes, 48 unresolved broadening,49−51 and even peak splitting in proline,7 of which TZ4 is an analogue. On the hypothesis that the shoulder may be due to conformers, we calculated the electronic energies and core level spectra of the lowest energy conformers of TZ4, as shown in Figure 2. The lowest energy conformer I has an OH···N hydrogen bond, similar to proline conformer 1b, and the calculated H···N distance is similar to the experimental value for proline 1a (1.915 Å).3 The second lowest energy proline conformers52 are those in which the OH is trans with respect to the amine nitrogen, rather than cis in 1a and 1b. The corresponding conformer IV of TZ4 has a rather high energy; there is no significant hydrogen bond as the shortest distance is 2.519 Å, between a methylene group and CO. TZ4 has an additional possibility to form intramolecular hydrogen bonds because of the presence of the S atom with its lone pairs, and this occurs in conformer III. The calculated hydrogen bond length, 2.270 Å, is comparable with the value calculated for a model system, 2.34 Å.53,54 There is not an

Figure 4. Core level spectra of TZ2 (blue) and the most stable conformer of TZ4 (red). (a) S 2p. (b) C 1s experimental spectra are compared with theoretical spectra (lower, darker curves). The theoretical spectra have been shifted by 0.21 eV (TZ2) and 0.45 eV (TZ4) to better match the lower binding energy peaks. (c) N 1s. (d) O 1s. dx.doi.org/10.1021/jp302950y | J. Phys. Chem. A 2012, 1 6166, 

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extensive literature on sulfur−hydrogen bonds, but the results in these papers indicate that the strength of the bond is comparable with that of oxygen−hydrogen bonds. This explains why this conformer is the second most stable. Conformer II does not contain a hydrogen bond, as the NH bond is oriented below the ring and away from the carboxyl group. It has an energy similar to conformer IV. In Table 3, the calculated core level binding energies are listed. These will be discussed below in the Discussion section. 3.2. Valence Spectra. Figure 5 shows the valence band spectrum of AZ2, compared with the ionization potentials

Figure 6. Charge densities of the highest three molecular orbitals of 2-azetidinone.

Figure 5. Valence band spectrum of 2-azetidinone. Inset: inner valence band region. Red curves: experiment. Blue curves: theory, assuming equal intensity for each ionic state, broadened by a fwhm of 0.25 eV.

calculated using the OVGF model. The spectroscopic pole strengths calculated using the OVGF model are all between 0.89 and 0.91, indicating that the single particle approximation used in the models is valid. The inset shows the inner valence spectrum, and the results are summarized in Table S3, Supporting Information. The strong peak at 10.2 eV and the shoulder at 10.48 eV are identified as due to ionization of the 4a″ (HOMO, highest occupied molecular orbital) and 15a′ orbitals (HOMO − 1), respectively. The experimental data indicate that the IPs are about 0.5 eV lower than calculated. The HOMO is very narrow, with an experimental width of 120 meV, implying that the minima of the ground and ionic state potential energy surfaces are very similar. The second, very broad feature in the spectrum at 13−15 eV was fitted with two peaks to extract binding energies, but the calculations show that it consists of four unresolved ionic states. The feature at 15.80 eV is due to a single ionic state, but the next peak at 16.66 eV arises from two ionizations. At 17.9 eV, there is a weak broad feature that does not appear in the calculated values; this may be a two-hole, one particle state. At higher energies, we enter the inner valence region, and we expect an increasing density of such states, and indeed, there is a strong continuum of emission from states attributed to two-hole, one particle states. Because the OVGF method deals only with the outer valence (as its name states), we have no predictions from this model for higher energies. We therefore turn to the SAOP method to identify the single-hole features in this energy range. Corresponding features are found in the theory and experiment, with shifts that vary between about 0.6 and 2.2 eV. The innermost valence orbitals, due to O 2s and N 2s, have binding energies similar to those of (carbonyl) oxygen and amino nitrogen in other small molecules.6 The orbital character of the highest molecular orbitals can be deduced from the plots of charge density in Figure 6. The HOMO is dominated by contributions from in-plane oxygen

lone pair orbitals, with additional contributions from C(2)− C(3) and C(2)−N in-plane orbitals. The HOMO − 1 is, however, dominated by a nitrogen lone pair orbital, hybridized with oxygen and C(4) orbitals, all of which are antisymmetric with respect to the reflection plane of the molecule. The atomic components of this orbital are in antiphase, suggesting that this is an antibonding orbital, but still of lower energy than the HOMO. The third highest molecular orbital is a C(3)−C(4) σ bonding orbital primarily composed of in-plane p-orbitals localized on these atoms but with contributions that include p-orbitals on all of the other atoms.

Figure 7. Outer valence band spectra of thiazolidine-2-carboxylic acid (red curves) and thiazolidine-4-carboxylic acid (blue curves). Experimental curves are shown above curves indicating theoretical peak positions.

The valence spectra of TZ2 and TZ4 are shown in Figure 7, simulated spectra are calculated at the OVGF/6-311++G** level, and Figure 8 shows the charge distribution of the three outermost orbitals of TZ2 and TZ4 calculated at the SAOP/ et-pVQZ level of theory. The full list of calculated energies is given in the Supporting Information (S4). The OVGF calculations agree well with the experimental data, for instance, for the first ionization potentials of TZ2 and TZ4 (peaks A), the differences between theory and experiment are only 60 and 130 meV, respectively. The theory also correctly predicts that the second broad band B has a larger energy separation from A, although, experimentally, this band is strongly broadened due to its Franck−Condon envelope. The first five spectral features dx.doi.org/10.1021/jp302950y | J. Phys. Chem. A 2012, 1 6166, 

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Figure 8. Charge distribution of the three outermost orbitals of TZ4 (upper) and TZ2 (lower), calculated at the SAOP/et-pVQZ level of theory.

of TZ2 (A to E) are seen to be due to single ionic states, while at higher energy, spectral crowding means that peaks F and G are due to about 5 ionic states. Features I and J may be due to single states. For TZ4, the agreement is a little less satisfactory, but the first four peaks are identified as due to ionization of orbitals 32a to 35a. The theory underestimates the energy separation between 31a and 32a (the fifth and fourth highest molecular orbitals), which appear experimentally as distinct peaks. From the calculations, it appears that the HOMO orbitals have the same characters in TZ2 and TZ4 and that they both have clear sulfur lone pair character. Indeed, the experimental spectra of the two compounds are very similar. The sharp first peaks are consistent with ionization of a nonbonding state, i.e., a sulfur lone pair, while the very broad second peaks are consistent with orbitals that have significant bonding character. The HOMO − 1 of TZ2 and TZ4 have leading contributions from the carbonyl oxygen and nitrogen lone pairs, but there are significant carbon and sulfur in-plane σ-bond contributions along the C(6)−C(2 or 4)−S(1)−C(5) axis. The HOMO − 2 orbitals of both molecules have similar contributions to these but with different phases and amplitudes. The leading contributions are still from carbonyl oxygen and nitrogen lone pairs.

4. DISCUSSION The rigid structure of AZ2 implies that we need consider only one conformer, which simplifies the spectra. While the N 1s and O 1s binding energies of AZ2 agree to within 160 meV with previous measurements of Greenberg et al.,8 they reported only a single C 1s binding energy at 291.80 eV, whereas three peaks are expected. Our results therefore correct this previous report. For TZ2 and TZ4, the calculations correctly predict a small energy shift of the S 2p level, with TZ2 having a slightly higher binding energy. The TZ4 spectrum is about 5% broader than that of TZ2; this may be due to different Franck−Condon factors, but as noted above, it is also a hallmark of the presence of conformers.7,48,51,55 Thomas and co-workers have investigated extensively the effect of conformational differences on line shape, carrying out high level electronic structure calculations, including anharmonicity and coupling of torsional and vibrational modes. Such calculations are beyond the scope of the present article, but the conclusions from their work can be used as a qualitative guide to interpretation of the present results. In their work, conformational effects were manifested mostly as changes in vibrational envelopes but sometimes as a change in ionization energy.50 These effects can be quite subtle, but they provide a fingerprint for the existence of populations of different conformers.

Article

The C 1s spectra, Figure 4b, have been assigned above, and we now return to discussion of the shoulder D′, which is much stronger in TZ4 than in TZ2. Once again, this can be interpreted as being either due to Franck−Condon effects or the presence of a second conformer. Previous reports of conformational effects and hydrogen bonding on core level spectra have concerned the atoms directly involved in the hydrogen bond, either nitrogen or oxygen. In this case, we observe an effect on a carbon atom, which is a second nearest neighbor to possible hydrogen bonds. Effects have been predicted6,51 but not observed unequivocally. Our calculations give some qualitative support to the hypothesis that the shoulder is due to a different conformer: a small shift of 50 meV is predicted for the second lowest energy conformer, III, while the experimental shift is 0.43 eV. In principle, very different Franck−Condon factors may enhance the apparent shift, as in the work of Thomas and coworkers.48−50 Another point is that the energy difference between conformers I and III is 21 kJ·mol−1, which would lead to a very small population of conformer III. However, the calculated energy is electronic, not Gibbs free energy, and this energy, and therefore the population, may be different at the temperature of the experiment. Thus, we conclude that this explanation is a hypothesis, but the evidence to support it is not strong. An alternative explanation is that the potential energy surfaces of the neutral and ionic states are such that they lead to an unusual Franck−Condon envelope. This explanation has the weakness that it also requires that there are significant differences between the isomers, which appears unlikely in a model of a single conformer for each isomer. The question arises as to why the conformer population of TZ4, and therefore the potential energy surfaces, is different from its analogue proline. The obvious answer is that the presence of sulfur modifies the energetics, and we may ask whether this is primarily an electronic or geometric effect. Since the electronegativities of C and S are very similar (2.55, 2.58), we would argue that the effect is primarily structural, that is, due to the difference in CC and CS bond lengths, which expand the thiazolidine ring. The perimeter of the pyrrolidine ring in proline is 7.514 Å,56 whereas in TZ4, it is 8.13 Å, due to the longer CS bonds. This difference seems to be sufficient to increase the energy of some conformers, while the geometry still allows conformer III (OH···S) to have a low energy.

5. CONCLUSIONS In the present study, the core and valence soft X-ray photoelectron spectra of 2-azetidinone and the 2- and 4-isomers of thiazolidine-carboxylic acid have been determined and analyzed using high quality quantum mechanical calculations. For AZ2, the present measurement results in three C 1s states at 291.19, 292.23, and 293.94 eV, one N 1s state at 405.84 eV, and one O 1s state at 537.48 eV. The N 1s and O 1s binding energies agree with previous results, while the C 1s energies correct apparent errors and update previous data. The core level spectra of TZ2 and TZ4 have been assigned by means of calculations, and the binding energy ordering of C 1s ionic states followed the trend expected on the basis of Hirshfeld charges, as did the C 1s states of 2-azetidinone. This implies that the core level shifts are largely determined by initial state effects for these compounds. A shoulder on the carboxylic C(6) 1s peak of TZ4 was identified as possibly originating from the presence of a second conformer in the gas phase. However, the evidence for this is not quantitative, and it is possible that it also arises from an dx.doi.org/10.1021/jp302950y | J. Phys. Chem. A 2012, 1 6166, 

The Journal of Physical Chemistry A unusual Franck−Condon envelope. The structures and spectra of the four lowest energy conformers of TZ4 have been calculated. The ground state has an OH···N hydrogen bond and the next highest energy conformer has an OH···S hydrogen bond. The calculated bond lengths are consistent with literature values.

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ASSOCIATED CONTENT

S Supporting Information *

Selected simulated geometrical parameters of AZ2, TZ2, and TZ4, comparison with experiment where available. Full list of valence orbital ionization energies of 2AZ, TZ2, and TZ4. This material is available free of charge via the Internet at http:// pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*Phone: +39 0403758584. Fax: +39 0403758565. E-mail: [email protected]. Present Addresses ∥

Forschungszentrum Jülich GmbH-IFF-IEE, 52425 Jülich, Germany. ⊥ Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, DK-8000 Aarhus C, Denmark. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS

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REFERENCES

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