Highly Selective Dissociation of a Peptide Bond ... - ACS Publications

May 19, 2015 - Peter Salén , Luca Schio , Robert Richter , Michele Alagia , Stefano Stranges ... Susanna Monti , Vincenzo Carravetta , Vitali Zhauner...
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Highly Selective Dissociation of a Peptide Bond Following Excitation of Core Electrons Yi-Shiue Lin,†,‡ Cheng-Cheng Tsai,⊥ Huei-Ru Lin,†,‡,§ Tsung-Lin Hsieh,†,‡ Jien-Lian Chen,‡,⊥ Wei-Ping Hu,*,⊥ Chi-Kung Ni,*,‡,∥ and Chen-Lin Liu*,† †

Scientific Research Division, National Synchrotron Radiation Research Center, Hsinchu 30076, Taiwan Institute of Atomic and Molecular Sciences, Academia Sinica, P.O. Box 23-166, Taipei 10617, Taiwan ⊥ Department of Chemistry and Biochemistry, National Chung Cheng University, Chia-Yi 62102, Taiwan § Department of Applied Chemistry, National Chiao Tung University, Hsinchu 30010, Taiwan ∥ Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan ‡

S Supporting Information *

ABSTRACT: The controlled breaking of a specific chemical bond with photons in complex molecules remains a major challenge in chemistry. In principle, using the K-edge absorption of a particular atomic element, one might excite selectively a specific atomic entity in a molecule. We report here highly selective dissociation of the peptide bonds in Nmethylformamide and N-methylacetamide on tuning the X-ray wavelength to the K-edge absorption of the atoms connected to (or near) the peptide bond. The high selectivity (56− 71%) of this cleavage arises from the large energy shift of X-ray absorption, a large overlap of the 1s orbital and the valence π* orbital that is highly localized on a peptide bond with antibonding character, and the relatively low bond energy of the peptide bonds. These characteristics indicate that the high selectivity on bond dissociation following core excitation could be a general feature for molecules containing peptide bonds.

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INTRODUCTION The use of photons to control the cleavage of a selected chemical bond in a complex molecule remains a challenge in chemistry. Photochemists traditionally varied the ratios of cleavages of chemical bonds on tuning monochromatic radiation, typically in the ultraviolet region, to the excitation energies of valence electrons of the precursor molecules, but the selectivities were limited. This method has been extended on combining infrared and ultraviolet photons and using vibrationally mediated photodissociation to control further the breakage of a chemical bond for small polyatomic molecules.1,2 An optimally shaped, strong-field laser pulse provides another method to control the cleavage of a specific chemical bond;3−5 shaping the pulse is a complicated process that has so far been applied only to few molecules. A third method utilizes the near-edge X-ray absorption of the core electrons of atomic species, in which the photon energy of excitation is sensitive to the chemical environment the particular atomic species. Such selective excitation can be specific to either one type of element or only to atoms of the same element at particular positions in a molecule. Near-edge X-ray absorption corresponds to an electron excitation from the 1s orbital of an atom to an empty valence orbital or to direct ionization. One major channel after excitation is Auger decay, followed by ejection of one or two electrons and dissociation. If the excitation energy remains localized near the initially excited atom for a short period of time, the chemical bonds around the excited atom might break readily. Element-selective or site© 2015 American Chemical Society

selective bond breaking following core-level excitation has been observed for molecules on a surface and in the gaseous phase,6−24 but the branching ratios (or selectivity) of these dissociation were typically small. Here we report the highly specific peptide bond dissociation following K-edge absorption. Combining experimental measurements and quantum-chemical calculations of near-edge Xray absorption fine structure (NEXAFS) spectra at carbon, nitrogen, and oxygen K-edges of N-methylformamide and Nmethylacetamide, we demonstrate that the bond dissociations are highly specific on the peptide bonds with X-ray photons at appropriately chosen energies. The high selectivity results from a large difference of energy of X-ray absorption between atoms connected to (or near) a peptide bond and atoms located elsewhere in the molecule, the large overlap of the 1s orbitals of these atoms and the valence π* orbital that is highly localized on the peptide bond with strong antibonding character, and the relatively low dissociation energy of the peptide bond. These properties, which are intrinsic characteristics of the peptide bond, suggest that the high selectivity on bond dissociation following core excitation could be a general feature for a large class of molecules containing peptide bonds. Received: May 7, 2015 Revised: May 13, 2015 Published: May 19, 2015 6195

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Figure 1. Experimental NEXAFS spectra in total-ion-yield mode (red) and calculated K-edge NEXAFS spectra at level LB94/6-31+G(d,p) (blue): (a)−(c): N-methylformamide; (d)−(f) N-methylacetamide. The calculated spectra are convoluted with a Lorentz function of half-width 50 meV. The energy shifts of calculated spectra are shown in each figure. The insets in (a) and (d) are the equilibrium geometries and the insets in (c) and (f) are the π* orbitals of N-methylformamide and N-methylacetamide, respectively.

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EXPERIMENTAL SECTION The experiments were performed with a homemade, orthogonal-acceleration, reflectron, time-of-flight, mass spectrometer (OA-R-TOF MS).24 A diffusive molecular beam was generated from an orifice of a sample cell (stainless steel) near 300 K. Soft X-rays from a synchrotron25 were directed into the ionization chamber with two bendable refocusing Kirkpatrick− Baez mirrors coated with Au. The X-rays crossed the diffusive molecular beam about 2 mm downstream from the orifice of the sample cell. The spot size of the X-rays was 0.4 mm × 0.2 mm at the intersection with the diffusive molecular beam. Molecules ionized by X-rays might dissociate into ionic and neutral fragments; the parent ions and ionic fragments were collimated with ion lenses on being repelled into the acceleration region of the mass spectrometer in the detection chamber. When the collimated ions arrived at the acceleration region, a pulsed voltage was applied to drive these ions into the flight tube for mass analysis. The rate of repetition of the pulsed voltage was 70 kHz. Ions were detected with a microchannelplate (MCP) detector (size 95 mm × 42 mm). The output signal from this detector was amplified and recorded with a time-of-flight multiscaler (FAST ComTec, model no. P7888, bin width 2 ns); a counting technique was utilized to accumulate the signal. The high-voltage pulse produced a large interference of the ion-detection system in the region of small mass (m/z ≤ 2 u); the mass spectra were recorded for only m/z > 2 u. X-rays were provided from Taiwan Light Source, undulator beamline BL05B1.25 The resolutions of X-rays were about 80, 70, and 150 meV at the carbon, nitrogen, and oxygen K-edges,

respectively. The resolutions for the isotopic experiments were about 160, 140, and 300 meV at the carbon, nitrogen, and oxygen K-edges, respectively. The photon energy was calibrated with absorption spectra of CO2 for both the carbon K-edge (at 290.77 eV)26 and the oxygen K-edge (at 535.4 eV),27 and with the N2 spectrum for the nitrogen K-edge (at 400.8 eV).28 Nmethylformamide, N-methylacetamide, N-methylformamide1-13C, and N-methylacetamide-15N (Sigma-Aldrich), and Nmethylformamide-d5 (CDN Isotope) were obtained from the indicated suppliers; all chemical compounds had purity >99% and were used without further purification.

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THEORETICAL CALCULATIONS The molecular structures of N-methylformamide and Nmethylacetamide in their ground electronic states were calculated using the hybrid density functional B3LYP with 6311+G(d,p) basis set. Time-dependent density-functional theory (TDDFT)29 was applied to calculate the carbon, nitrogen, and oxygen K-edge NEXAFS spectra. The coreexcitation TDDFT calculation was performed with the LB9430 functional within the subspace of single excitations from the core (1s) orbitals with the Tamm−Dancoff approximation31 without relativistic corrections.29 This method has been shown to work satisfactorily for X-ray absorption spectra in our previous work32 and by Stener and co-workers.30,33 The standard Pople type basis set 6-31+G(d,p) was used to calculate the NEXAFS spectra. The basis set was selected on the basis of our experience that the LB94/6-31+G(d,p) calculation generally reproduces the experimental NEXAFS spectra satisfactorily without the need of significant energy 6196

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methyl group that is connected to the carbonyl group. All other transitions have small oscillator strengths and correspond to excitations from the 1s orbital to various Rydberg orbitals that are delocalized over the entire molecule. Detailed information about these orbitals is presented in the Supporting Information. The K-edge spectra of amino acids and small peptides have been studied extensively;36−48 they differ slightly between the gaseous phase and the solid state. The spectra of protonated/ deprotonated peptides also differ from those of neutral species. The transitions C 1s → π*CO, N 1s → π*NC, and O 1s → π*CO of neutral gaseous amino acids and peptides generally have large oscillator strengths at 288, 402, and 532 eV, respectively. Our assignments of N-methylformamide and Nmethylacetamide in these regions are similar to the assignments in previous work. B. Dissociation of N-Methylformamide. Figures 2, 3 and 4 show mass spectra of N-methylformamide after exciting the

shifts. The ground-state geometry was calculated with the Gaussian 09 Rev. D01 program34 and the NEXAFS calculation with the Q-CHEM 4.1 program.35

Figure 2. Mass spectra of N-methylformamide after transitions 1s → π* at the carbon K-edge (288.08 eV). Mass spectra from isotopically substituted N-methylformamide are shown for comparison in (b) (DCOND(CD3)) and (c) (H13CONH(CH3)). The formulas for each molecule are labeled. If there is more than one possible formula for one mass to charge ratio, the ones with large branching ratios are labeled as upper ones. Details of the branching ratio of each component are listed in the Supporting Information. The insets show the probabilities of cleavage of peptide bonds and the location of charge on each side of a fragment.

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RESULTS AND DISCUSSION A. Spectra. Figure 1 presents the experimental absorption spectra of carbon, nitrogen, and oxygen at their K-edges in total-ion-yield mode in the gaseous phase and the corresponding calculated spectra of N-methylformamide and N-methylacetamide. The agreement between the experimental and theoretical spectra is satisfactory. The assignments of transitions (from the 1s orbital of a particular atom to a particular virtual orbital) are listed in the Supporting Information. All spectra are dominated by one absorption line, i.e., at 288 eV for the C Kedge, at 402 eV for the N K-edge, and at 532 eV for the O Kedge. The calculations indicate that this major absorption line corresponds to transitions from the 1s orbitals of the carbonyl carbon atom, the nitrogen atoms connected to the peptide bond, or the carbonyl oxygen atom to the same valence orbital, i.e., the lowest π* orbital. This π* orbital, located in the region of the carbonyl group and the peptide bond, has a strong antibonding character along the peptide bond and the CO bond, as shown in the inset of Figure 1c,f. For Nmethylacetamide, this π* orbital further delocalizes to the

Figure 3. Mass spectra of N-methylformamide after transitions 1s → π* at the nitrogen K-edge (401.74 eV). Mass spectra from isotopically substituted N-methylformamide are shown for comparison in (b) (DCOND(CD3)) and (c) (H13CONH(CH3)). The insets show the probabilities of cleavage of peptide bonds and the location of charge on each side of a fragment.

1s → π* transition at the carbon, nitrogen, and oxygen K-edges, respectively. The mass spectra of N-methylformamide at the other resonant excitation energies are similar, but the relative intensities vary. They are presented in the Supporting Information. The dominant products of N-methylformamide, HCONH(CH3), are ionic fragments with ratios of mass to charge in the range m/z = 26−30 u. These products can be generated from three possible dissociation paths, the first of which is the cleavage of a peptide bond, generating the ion NHCH3+ (m/z = 30 u), and the ionic fragments with m/z = 26−29 u are formed 6197

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CH+ (m/z = 29 u), and CO+ (m/z = 28 u) is formed after elimination of an additional hydrogen atom. In the third path, the ionic product HCNH+ (m/z = 28 u) is produced on breaking both CO and NCH3 bonds, and the ionic fragments with m/z = 27 and 26 u are generated after elimination of one and two additional hydrogen atoms, respectively. The mass spectra of isotopically substituted N-methylformamide, H13CONH(CH3) and DCOND(CD3), with excitation at the same wavelengths are also presented in Figures 2−4. The possible dissociation paths described above diminish when these mass spectra are compared. For instance, the intensity of the ionic product with m/z = 30 u from H13CONH(CH3) increased relative to that from HCONH(CH3), which is possible only if fragment H13CO+ is formed on cleavage of the peptide bond. The intensity of an ionic fragment with m/z = 28 u remained the largest in the mass spectra of H13CONH(CH3), indicating that its composition excludes a 13C atom. Thus, the only possible formula with m/z = 28 u is NCH2+ from cleavage of the peptide bond. The ionic product with m/z = 30 u in HCONH(CH3) becomes m/z = 34 u in DCOND(CD3), indicating that the product is DNCD3+ via breaking a peptide bond. Comparing the mass spectra of the isotopically substituted N-methylformamide, we calculated the branching ratios of each dissociation path and the fraction of charge locations after bond cleavage. Details of the calculations are shown in the Supporting Information. The deduced dominant channels are illustrated in the inset of Figures 2−4. The branching ratios after the cleavage of the peptide bond are as high as 0.61 ± 0.05 for the O K-edge, 0.71 ± 0.05 for the N K-edge, and 0.59 ± 0.07 for the C K-edge. The ratio of the charge locations after cleavage of the peptide bond (to produce CH3NH and CHO) is about 2 ± 1:1; the main ionic products are CH2N+ and CHO+. Figure 5 shows the branching ratios as a function of photon energy for major ionic products from cleavage of the peptide bond. There are large increases at the transition

Figure 4. Mass spectra of N-methylformamide after transitions 1s → π* at the oxygen K-edge (531.79 eV). Mass spectra from isotopically substituted N-methylformamide are shown for comparison in (b) (DCOND(CD3)) and (c) (H13CONH(CH3)). The insets show the probabilities of cleavage of peptide bonds and the location of charge on each side of a fragment.

from loss of one to four additional hydrogen atoms. The second path results from a cleavage of the same peptide bond but with charge located on the other side to form the ion O

Figure 5. Branching ratios (as percent) of major ionic products after cleavage of the peptide bond of N-methylformamide at the (a) carbon K-edge, (b) nitrogen K-edge, and (c) oxygen K-edge. Some major components from cleavage of the peptide bond, m/z = 28 and 29 u, are enhanced after excitation of transition 1s → π* located at 288 eV for the C K-edge, 402 eV for the N K-edge, and 532 eV for the O K-edge. 6198

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The Journal of Physical Chemistry A energies of 1s → π*, indicating that cleavage of the peptide bond is specifically enhanced at this transition. C. Dissociation of N-Methylacetamide. The mass spectra of N-methylacetamide after the core excitation to the lowest π* orbital at carbon, nitrogen, and oxygen K-edges, respectively, are shown in Figures 6, 7, and 8. The ionic

Figure 7. Mass spectra of N-methylacetamide after transitions 1s → π* at the nitrogen K-edge (401.8 eV). Mass spectra from isotopically substituted N-methylacetamide are shown for comparison in (b) (CH3CO15NH(CH3)). The insets show the probabilities of cleavage of peptide bonds and the location of charge on each side of a fragment.

Figure 6. Mass spectra of N-methylacetamide after transitions 1s → π* at the carbon K-edge (288.2 eV). Mass spectra from isotopically substituted N-methylacetamide are shown for comparison in (b) (CH3CO15NH(CH3)) and (c) (CH3CONH(CD3)). The blue curve in (c) is reproduced from ref 49 with permission from the PCCP Owner Societies. The formulas from nonisotopically substituted molecules are labeled. If there is more than one possible formula for one mass to charge ratio, the ones with large branching ratios are labeled as upper ones. Details of the branching ratio of each component are listed in the Supporting Information. The insets show the probabilities of cleavage of peptide bonds and the location of charge on each side of a fragment.

Figure 8. Mass spectra of N-methylacetamide after transitions 1s → π* at the oxygen K-edge (532.1 eV). Mass spectra from isotopically substituted N-methylacetamide are shown for comparison in (b) (CH3CO15NH(CH3)). The insets show the probabilities of cleavage of peptide bonds and the location of charge on each side of a fragment.

fragments of CH3CONH(CH3) have the largest intensities in the region m/z = 38−43 u. There are four possible paths of dissociation to produce these ions: (1) COCH3+ (m/z = 43 u) is produced from the cleavage of the N−CO peptide bond, and additional elimination of H atoms generates ions with m/z = 42−40 u; (2) CONH+ (m/z = 43 u) is produced from the cleavage of both OCCH3 and HNCH3 bonds, and elimination of an additional H atom generates ions with m/z = 42 u; (3) CNHCH3+ (m/z = 42 u) arises from the cleavage of the CO and OCCH3 bonds, and elimination of an additional H atom produces ions with m/z = 41−38 u; (4) NHCCH3+ (m/z = 42 u) results from the cleavage of CO bond and NCH3 bonds, and elimination of additional H atom(s) produces ions with m/z = 41−38 u. The mass spectra from isotopically substituted CH3CO15NH(CH3) show that the largest intensity in this region remains at m/z = 43 u, which

indicates that ions with m/z = 43 u result from only the first dissociation path, corresponding to cleavage of the peptide bond. The relative intensities of ions between m/z = 40 and 42 u also remained unchanged, indicating that they resulted mainly from the same dissociation channel. An ionic fragment with m/ z = 38 u became m/z = 39 u from CH3CO15NH(CH3), which is consistent with the proposed dissociation paths 3 and 4, but the contributions from these paths were small, as illustrated by the small intensity of ions with m/z = 38 u. The ionic fragments with m/z = 24−30 u that also showed large intensities can be produced from the following four possible dissociation paths: (1) CCH3+ (m/z = 27 u) is produced from the cleavage of CO and OCN bonds, and elimination of additional H atoms yields ions with m/z = 26− 6199

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Figure 9. Branching ratios (as percent) of major ionic products after cleavage of the peptide bond of N-methylacetamide at the (a) carbon K-edge, (b) nitrogen K-edge, and (c) oxygen K-edge. Some major components after cleavage of the peptide bond, ions with m/z = 28, 42, and 43 u, are enhanced after excitation with transition 1s → π* located at 288 eV for the C K-edge, 402 eV for the N K-edge, and 532 eV for the O K-edge.

and NHCH3) is about 1:1.4 ± 0.3, and the main ionic products are CH3CO+ (m/z = 43 u) and NCH2+ (m/z = 28 u). These calculations are described in detail in the Supporting Information. Figure 9 shows the ratios of ion intensity as a function of photon energy for major ionic products from cleavage of the peptide bond, indicating that this cleavage is specifically enhanced at the excitation energies of 1s → π* transitions. D. Selectivity. The ionic products resulting from fragmentation at a specific site after excitation of a core electron have been observed in many experiments,6−24 which produced particular fragments representing dissociation at specific sites, but many other fragments were produced at the same wavelength. The branching ratios of these particular fragments, i.e., the ions produced from dissociation at a specific site versus the total ionic fragments, are typically small for polyatomic molecules. For example, Okada and co-workers found the branching ratios of specific dissociation from 2-, 3-, and 4-pyridine to be only 1.2−1.9%.50 Kawasaki et al. found the branching ratio of product CD3+ to increase from 5.9% (excited at 535.1 eV) to 12.8% (excited at 531.9 eV) from CH3COOCD3.51 Although the K-edge spectra of amino acids and small peptides have been studied extensively, the dissociation pathways of peptides after core excitation has not been thoroughly investigated.49,52 We demonstrate in the current study that the branching ratios after breakage of the peptide bond can be as high as 0.56−0.71. These large branching ratios of cleavage of the peptide bond in N-methylformamide and Nmethylacetamide can be rationalized according to the following characteristics. First, the K-edge absorption lines of the carbonyl O atom and the C and N atoms that are connected to the peptide bond are widely separated from most K-edge absorption lines of other atoms, such that one can preferentially excite these atoms exclusively. Second, the oscillator strengths of the transitions from the 1s orbital of these atoms to the π* orbital are large. This is partly because the π* orbital is highly localized around the OC−N bond and has a large overlap

24 u.; (2) CO+ (m/z = 28 u) is produced from the cleavage of CCH3 and OCN bonds; (3) CNH+ (m/z = 27 u) is produced from cleavage of the CO, CCH3, and NCH3 bonds, and elimination of an additional H atom generated ions with m/z = 26 u; (4) NHCH3+ (m/z = 30 u) is produced from cleavage of the OCN peptide bond, and elimination of additional H atom generates ions with m/z = 29−26 u. The mass spectra from isotopically substituted compound CH3CO15NH(CH3) show that ions with m/z = 30−26 u became m/z = 31−27 u with little alteration of the relative intensities. This indicates that the main dissociation path is the cleavage of the peptide bond (the fourth path). The intensities of ions with m/z = 58−50 u and 12−15 u are small, and these ions result from cleavage of the CO bond and the OCCH3 or NCH3 bond, respectively. The mass spectra of CH3CONH(CH3) and CH3CONH(CD3) after excitation at the C K-edge have been reported, but the formulas of many fragments were undecided.49 On comparison with the mass spectra of the isotopically substituted compound CH315NHCO(CH3) in this work, the formulas of these fragments are unambiguously determined. Moreover, we correct the assignments of two fragments made in the preceding work.49 We suggest that the fragment ion with m/ z = 31 u is produced from the H atom migration from the moiety of CH3CO to the moiety of NHCH3 followed by the cleavage of the peptide bond, which yields ions with m/z = 32 u (15NH2CH3) in CH3CO15NH(CH3) and m/z = 34 u (NH2CD3+) in CH3CONH(CD3). A fragment ion with m/z = 29 u (NCH3+) is generated on cleavage of the peptide bond and elimination of an additional H atom, which yields ions with m/z = 30 u in CH3CO15NH(CH3) and m/z = 32 u (NCD3+) in CH3CONH(CD3). The insets of Figures 6−8 illustrate branching ratios of the major dissociation channels calculated from the mass spectra. The branching ratios after cleavage of the peptide bond are as high as 0.56 ± 0.09 for the O K-edge, 0.63 ± 0.10 for the N Kedge, and 0.65 ± 0.09 for the C K-edge. The ratio of charge locations after cleavage of the peptide bond (to yield CH3CO 6200

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The Journal of Physical Chemistry A with the 1s orbitals of these atoms. This large oscillator strength makes the selective excitation more effective. Third, the π* orbitals have an antibonding character along the peptide bond. It is understood that there are many possible final Auger states after the core excitation, and then the excited molecules have to pass through many intermediate states before bond cleavage actually occurs. The various Auger states and intermediate states add the complexity in the dissociation process. However, if the excited electron could remain in the antibonding orbital long enough (after molecules pass through all the intermediate states before dissociation occurs), it can be an additional factor to enhance the selectivity of the peptide bond cleavage. Furthermore, the peptide bond is a relatively weak chemical bond in these molecules. If the amount of energy left in the parent ion is not large after resonance Auger decay, breakage of a peptide bond might become one of major dissociation channels even after energy is randomized among various vibrational degrees of freedom. As these properties are general characteristics of the OC−N moiety, we expect that the high selectivity may not be limited to the molecules that we studied. That is, the highly selective dissociation of a peptide bond after excitation of a core electron could be applicable to other molecules containing a peptide bond.

ACKNOWLEDGMENTS

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REFERENCES

(1) Crim, F. F. State- and Bond-Selected Unimolecular Reactions. Science 1990, 249, 1387−1392. (2) Crim, F. F. Bond-Selected Chemistry: Vibrational State Control of Photodissociation and Bimolecular Reaction. J. Phys. Chem. 1996, 100, 12725−12734. (3) Levis, R. J.; Menkir, G. M.; Rabitz, H. Selective Bond Dissociation and Rearrangement with Optimally Tailored, Strong-Field Laser Pulses. Science 2001, 292, 709−713. (4) Laarmann, T.; Shchatsinin, I.; Singh, P.; Zhavoronkov, N.; Gerhards, M.; Schulz, C. P.; Hertel, I. V. Coherent Control of Bond Breaking in Amino Acid Complexes with Tailored Femtosecond Pulses. J. Chem. Phys. 2007, 127, 201101. (5) Assion, A.; Baumert, T.; Bergt, M.; Brixner, T.; Kiefer, B.; Seyfried, V.; Strehle, M.; Gerber, G. Control of Chemical Reactions by Feedback-Optimized Phase-Shaped Femtosecond Laser Pulses. Science 1998, 282, 919−922. (6) Wada, S.-i.; Sumii, R.; Isari, K.; Waki, S.; Sako, E. O.; Sekiguchi, T.; Sekitani, T.; Tanaka, K. Active Control of Chemical Bond Scission by Site-Specific Core Excitation. Surf. Sci. 2003, 528, 242−248. (7) Eberhardt, W.; Stöhr, J.; Feldhaus, J.; Plummer, E. W.; Sette, F. Correlation between Electron Emission and Fragmentation into Ions Following Soft-X-ray Excitation of the N2 Molecule. Phys. Rev. Lett. 1983, 51, 2370−2373. (8) Eberhardt, W.; Sham, T. K.; Carr, R.; Krummacher, S.; Strongin, M.; Weng, S. L.; Wesner, D. Site-Specific Fragmentation of Small Molecules Following Soft-X-ray Excitation. Phys. Rev. Lett. 1983, 50, 1038−1041. (9) Wada, S.-i.; Kizaki, H.; Matsumoto, Y.; Sumii, R.; Tanaka, K. Selective Chemical Bond Breaking Characteristically Induced by Resonant Core Excitation of Ester Compounds on a Surface. J. Phys.: Condens. Matter 2006, 18, S1629−S1653. (10) Plekan, O.; Feyer, V.; Ptasińska, S.; Tsud, N.; Cháb, V. r.; Matolín, V. r.; Prince, K. C. Photoemission Study of Thymidine Adsorbed on Au(111) and Cu(110). J. Phys. Chem. C 2010, 114, 15036−15041. (11) Knotek, M. L. Atom-Specific Bond Breakage. Nature 1981, 291, 452−453. (12) LeBrun, T.; Lavollée, M.; Simon, M.; Morin, P. Dissociation Dynamics of Core Excited N2O. J. Chem. Phys. 1993, 98, 2534−2540. (13) Habenicht, W.; Baiter, H.; Müller-Dethlefs, K.; Schlag, E. W. Selective Fragmentation of Nitrous Oxide by Site-Specific N (1 s) Excitation Using Soft X-ray Synchrotron Radiation. Phys. Scr. 1990, 41, 814−818. (14) Liu, X. J.; Prümper, G.; Kukk, E.; Sankari, R.; Hoshino, M.; Makochekanwa, C.; Kitajima, M.; Tanaka, H.; Yoshida, H.; Tamenori, Y.; et al. Site-Selective Ion Production of the Core-Excited CH3F Molecule Probed by Auger-Electron−Ion Coincidence Measurements. Phys. Rev. A: At., Mol., Opt. Phys. 2005, 72, 042704. (15) Naves de Brito, A.; Sundin, S.; Marinho, R. R.; Hjelte, I.; Fraguas, G.; Gejo, T.; Kosugi, N.; Sorensen, S. L.; Björneholm, O. Memories of Excited Femtoseconds: Effects of Core−Hole Localization after Auger Decay in the Fragmentation of Ozone. Chem. Phys. Lett. 2000, 328, 177−187. (16) Erman, P.; Karawajczyk, A.; Rachlew, E.; Stankiewicz, M.; Yoshiki Franzén, K. State Selective Photon Induced Formation of Triply Charged Fragments from the Core Excited OCS Molecule. J. Chem. Phys. 1997, 107, 10827−10828. (17) Nagaoka, S.-i.; Fukuzawa, H.; Pruemper, G.; Takemoto, M.; Takahashi, O.; Yamaguchi, K.; Kakiuchi, T.; Tabayashi, K.; Suzuki, I. H.; Harries, J. R.; et al. A Study to Control Chemical Reactions Using

CONCLUSIONS We demonstrate the highly selective dissociation of the peptide bonds in N-methylformamide and N-methylacetamide after excitation of a core electron, which was achieved on tuning the X-ray wavelength to the K-edge absorption of the atoms connected to (or near) the peptide bond. The selectivities are much higher than those typically observed. The high selectivity after cleavage of a peptide bond is related to the general properties of the OCN moiety. We propose that the highly specific dissociation discovered in the current study could be a general feature for molecules containing peptide bonds. ASSOCIATED CONTENT

S Supporting Information *

The assignments of NEXAFS spectra of N-methylformamide and N-methylacetamide at carbon, nitrogen, and oxygen Kedges are listed in Tables S1 and S2, respectively. The transition destination orbitals calculated at level LB94/631+G(d,p) are presented in Figures S1 and S2. Mass spectra after dissociation of N-methylformamide and N-methylacetamide at some selected photon energies are shown in Figures S3 and S4. The details of dissociation paths and branching ratios of cleavage of the peptide bond for both molecules are represented in the end of the Supporting Information, in which Figures S5−S7 help explain the dissociation channels and calculated branching ratios are listed in Tables S3−S8. The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jpca.5b04415.

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Ministry of Science and Technology (MOST), Taiwan, under contract NSC 102-2113-M-213-003-MY2, and the Thematic Research Program, Academia Sinica, Taiwan under grant AS102-TP-A08 supported this work.

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AUTHOR INFORMATION

Corresponding Authors

*W.-P. Hu. E-mail: [email protected]. *C.-K. Ni. E-mail: [email protected]. *C.-L. Liu. E-mail: [email protected]. Notes

The authors declare no competing financial interest. 6201

DOI: 10.1021/acs.jpca.5b04415 J. Phys. Chem. A 2015, 119, 6195−6202

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DOI: 10.1021/acs.jpca.5b04415 J. Phys. Chem. A 2015, 119, 6195−6202