Metastable Protonated Cinchonidine - ACS Publications - American

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Exotic Protonated Species Produced by UV-Induced Photofragmentation of a Protonated Dimer: Metastable Protonated Cinchonidine Published as part of The Journal of Physical Chemistry A virtual special issue “Spectroscopy and Dynamics of Medium-Sized Molecules and Clusters: Theory, Experiment, and Applications”. Ivan Alata,† Debora Scuderi,‡ Valeria Lepere,† Vincent Steinmetz,‡ Fabrice Gobert,‡ Loïc Thiao-Layel,‡ Katia Le Barbu-Debus,† and Anne Zehnacker-Rentien*,† †

Institut des Sciences Moléculaires d’Orsay (ISMO), CNRS, Univ Paris-Sud, Université Paris Saclay, F-91405 Orsay, France Laboratoire de Chimie Physique (LCP), CNRS, Univ Paris-Sud, Université Paris Saclay, F-91405 Orsay, France

‡

S Supporting Information *

ABSTRACT: A metastable protonated cinchona alkaloid was produced in the gas phase by UV-induced photodissociation (UVPD) of its protonated dimer in a Paul ion trap. The infrared multiple photon dissociation (IRMPD) spectrum of the molecular ion formed by UVPD was obtained and compared to DFT calculations to characterize its structure. The protonation site obtained thereby is not accessible by classical protonation ways. The protonated monomer directly formed in the ESI source or by collision-induced dissociation (CID) of the dimer undergoes protonation at the most basic alkaloid nitrogen. In contrast, protonation occurs at the quinoline aromatic ring nitrogen in the UVPD-formed monomer.

1. INTRODUCTION Protonated molecules play an important role in chemistry and biology, as stable species or reactive intermediates. Protonation may influence the chemical and physical properties of a molecule, modifying its structure and the chemical processes in which it is involved. These modifications influence in turn biological properties such as protein structure,1 ligand−protein interactions,2 or the operating of K+/Na+ pumps.3 Transient protonated species also play an important role in nucleophilic reactions.4,5 Molecular structure strongly depends on the interactions with the environment, in particular with the solvent. Therefore, complete isolation in the gas phase is required to get the intrinsic molecular properties.6−12 This statement is especially true for charged systems, which interact with the surroundings by strong electrostatic interactions. Moreover, their high sensitivity to charge distribution makes also molecular interactions, for example, those related to stereospecificity, highly dependent on protonation. It is therefore interesting to compare structural properties of neutral molecules with their protonated counterparts.13,14 Over the past decade, development of several experimental techniques and ions sources has allowed the characterization of structure, reactivity, and electronic properties of many protonated molecules in the gas phase.8,11,12,15−26 Electrospray ionization (ESI) coupled with room-temperature or cryogenic © XXXX American Chemical Society

ion traps mostly forms protonated species that are stable in solution, although the question of kinetic trapping vs thermodynamic equilibrium is still open.27 Moreover, collision-induced dissociation (CID) or photoinduced dissociation can be used for forming metastable species like reaction intermediates.21,28,29 Supersonic expansions coupled with electric discharge8,11 or electron impact30 have also been used for forming cold protonated ions. Metastable species involving protonation of unsaturated bonds have attracted much interest in the context of chemical reactivity.8,11,30−32 In this respect, aromatic protonated species have attracted particular attention due to their role as reaction intermediates in aromatic electrophilic reactions.33−35 Protonation spontaneously occurs at the most basic site, although changes in the ESI or supersonic expansion conditions may lead to the formation of less stable isomers.34,36 Electronic excitation can also modify the acido-basic properties. Photoinduced proton or hydrogen-transfer reactions permit transfer of the proton or hydrogen atom to the most basic site in the electronic excited state. This so-called excited-state protontransfer (ESPT) reaction has been widely studied in solution or isolated conditions.37−42 It is especially effective in quinoline Received: July 7, 2015 Revised: September 6, 2015

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DOI: 10.1021/acs.jpca.5b06506 J. Phys. Chem. A XXXX, XXX, XXX−XXX

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The Journal of Physical Chemistry A derivatives43−48 where it is able to induce a photoactivated molecular motion.49 ESPT also plays an important role in the electronic excited-state dynamics of protonated biomolecules, where it results to a short-lived metastable species undergoing fast fragmentation or deactivation.50−52 Last, ESPT has been used in gas phase complexes for photochemical protonation of biomolecules.53 In this work, we resort to excited-state proton transfer in the protonated cinchonidine dimer (Cd)2H+ isolated in an ion trap to prepare a metastable protonated molecule inaccessible by other methods. Cinchonidine belongs to the Cinchona alkaloids family, well-known for its numerous applications in pharmaceutical and medical fields, as well as analytical chemistry and catalysis.54−59 It is characterized by a quinoline aromatic ring connected to an alkaloid tertiary amine through a chiral alcohol (Figure 1). Most of the desirable properties of the

Protonation has important consequences on the photophysics of cinchona alkaloids. The neutral forms display three low-lying transitions localized on the aromatic ring, namely, the nπ* transition, also observed in quinoline,67,68 and two ππ* transitions typical of substituted naphthalene.69−72 Last, a charge-transfer nπ* transition from the alkaloid nitrogen to the aromatic ring has been evidenced in polar solvents by its very weak Stokes-shifted fluorescence.73 Protonation of the alkaloid nitrogen removes the latter transition and results in a dramatic increase of the quinine fluorescence quantum yield.37 The absorption spectrum of the protonated (Cd)2H+ dimer has been recorded in a Paul ion trap by monitoring the UVPD fragments. UVPD of the (Cd)2H+ (m/z 589) dimer shows two dissociation paths.21,22 The first one is the loss of neutral Cd (294 amu) and protonated monomers CdH+ (m/z 295). The second one consists of the loss of a neutral alkaloid radical (136 amu) and the corresponding radical cation (m/z 453). This fragmentation channel was not observed by CID of the dimer and was unique to UVPD. The radical cation (m/z 453) was spectroscopically probed in the region of the OH and NH stretches as well as in the fingerprint region, which allowed proposing a structure and a mechanism of formation.21 In the present work, we investigate the UVPD channel leading to protonated and neutral monomers. The aim of this work is to assess whether the protonated monomer formed by UVPD, denoted CdH+UVPD hereafter, has the same structure as the native species produced by ESI, denoted CdH+ESI, or by CID of the protonated dimer, denoted CdH+CID. To this end, IRMPD spectra are obtained for the protonated CdH+ monomer produced by the three different methods, namely, directly in the ESI source, by CID of the protonated dimer, and last by UVPD. DFT calculations help to interpret the experimental spectra in terms of most stable structures and protonation sites.

Figure 1. Structure of (−)-cinchonidine (1S,3R,4S,8S,9R). The two protonation sites are denoted by Nalk or Narom.

cinchona alkaloids have been traced back to the structural constraints around the chiral linker and involve the shape of the chiral socket formed by the two bulky nitrogen-containing moieties.60 The most stable structure of neutral cinchona alkaloids has been determined in the gas phase by double resonance IR−UV spectroscopy.61,62 It is of γ-open type, like the most stable structure in solution.60,61,63 The open denomination refers to the extended geometry of the aromatic and alkaloid frames, and γ refers to the 180° dihedral angle of the chiral hinge C8−C9− O−H.60,63 The γ structure observed shows no hydrogen bond between OH and the alkaloid nitrogen. Closed structures, in which the alkaloid folds over the aromatic ring, have also been evidenced at room temperature with diverse C8−C9−O−H dihedral angles.60,61,63,64 The corresponding geometries are denoted by α, β, γ for a value of +60°, −60° and +180°, respectively.63 NMR studies have shown that protonation at the alkaloid nitrogen influences the structure of cinchona alkaloids in solution.65 However, these effects have been related to the interaction with the counterions more than the conformational preferences of the protonated alkaloid itself.65,66 Protonated cinchona alkaloids have been characterized in the gas phase by IRMPD spectroscopy.66 The IRMPD spectrum in the hydride stretch region has been interpreted in terms of the coexistence, at room temperature, of open and closed forms. The protonated dimer (Cd)2H+ produced by ESI has been spectroscopically characterized in a Paul ion trap by IRMPD spectroscopy.66 As observed in the monomer, protonation occurs at the alkaloid nitrogen. The most stable dimer observed involves a very strong hydrogen bond from the protonated alkaloid nitrogen of the protonated species to the quinoline nitrogen of the neutral. The resulting structure is almost a shared proton.

2. EXPERIMENTAL AND THEORETICAL METHODS 2.1. Experimental Section. Cinchonidine was purchased from Sigma-Aldrich and used without further purification. A 1 mM stock solution was further diluted in a 50:50 water− methanol solution to a final concentration of 100 μM. The pH was adjusted to ∼5 by adding 5 μL of formic acid to the final solution. A modified Paul ion trap (Bruker, Esquire 3000+) described previously20 was employed for probing the 900−1700 range of all the studied species and for probing the 3000−3800 cm−1 region of CdH+UVPD. This experimental set up was recently modified by drilling a conical hole of 2 mm diameter in the ring electrode to allow simultaneous focalization of three laser beams, namely, UV laser, free-electron laser (FEL) or OPO/ OPA, and CO2 laser, in the center of the trap.21 The laser beams entered the trap through a diamond window oriented at Brewster angle to obtain maximum laser intensity in the trap. A 7T Fourier transform ion cyclotron resonance (FT-ICR) hybrid mass spectrometer (Bruker, Apex Qe) coupled to the OPO/OPA was used for probing the hydride stretch region of CdH+ESI and CdH+CID, as already described in detail.74,20 The ICR setup was preferred for this region because of the low fragmentation efficiency of CdH+ESI and CdH+CID, which would make the acquisition in the Paul trap difficult because of relaxation due to collisions with He. CdH+ and (Cd)2H+ ions were generated by electrospray ionization (ESI). ESI conditions in the Paul ion trap were as follows: flow rate of 150 μL/h, dry gas flow of 2.5 L/mn, B


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Figure 2. (a) CID-MS2 mass spectrum of CdH+ESI (RF amplitude = 0.30 fragmentation time = 1 s). (b) CID-MS3 mass spectrum of CdH+ESI (RF amplitude = 0.30 fragmentation time = 1 s). (c) CID-MS3 mass spectrum of CdH+UVPD (RF amplitude = 0.12 fragmentation time = 1 s).

nebulizer pressure of 2.2 bar, capillary voltage of −4200 V, and dry gas temperature of 200 °C. ESI conditions in the FT-ICR were as follows: flow rate of 120 μL/h, spray voltage of −4000 V, dry gas flow of 4.5 L/s, nebulizer pressure of 1.5 bar, and dry gas temperature of 150 °C. IRMPD spectra of the three CdH+ samples were recorded with the following experimental conditions. • CdH+ESI (m/z 295) obtained directly by electrospraying the cinchonidine solution in the conditions described above was mass-selected in a 5 Da mass window. • CdH+CID was formed either in the Paul ion trap or in the ICR. In both cases, (Cd)2H+ (m/z 589) was first mass selected in a 5 Da window. Fragmentation was obtained by collision with He in the Paul trap by applying a radiofrequency (RF) voltage of amplitude 0.1 during 1 s. In the 7T FT-ICR mass spectrometer, (Cd)2H+ was first mass selected in a quadrupole mass filter then fragmented through multiple collisions with Ar in a pressurized hexapole by using a DC offset of the order of −1.5 V. The product ion CdH+CID (m/z 295) was then isolated again in a MS3 step in a 5 Da window. • CdH+UVPD was formed in the Paul ion trap in the following way. (Cd)2H+ was first mass selected and isolated in a 5 Da window. It was then photofragmented for 1 s by the fourth harmonic of a Nd:YAG laser at 266 nm (Minilite Continuum, 500 μJ/pulse, 10 Hz). The laser was focused at the center of the trap by a 1000 mm focal length lens. The photoproduct ion CdH+UVPD (m/z 295) was then isolated again in a MS3 step in a 5 Da window. IRMPD spectra in the 900−1700 cm−1 region were obtained by means of the infrared free electron laser (FEL) at CLIO (Centre Laser Infrarouge d’Orsay)75 for the three CdH+ species. The power of the FEL is 2 W between 900 and 1100 cm−1. It gradually decreases from 2 to 1 W between 1100 and 1600 cm−1 and then falls to 0.5 W at 1500 cm−1. An IR optical parametric oscillator (LaserVision OPO, 20 Hz, 5−10 mJ/pulse) was used in the 3000−3800 cm−1 region. For the spectra recorded in the Paul ion trap, both lasers were focused

by an OFHC (oxygen free high thermal conductivity copper for cryogenic application) parabolic mirror with 350 mm focal length and the irradiation duration was set to 1 s. To enhance the fragmentation yield, additional pulsed radiation of a CO2 laser (Universal Laser system, 10 W at CW operation, λ = 10.6 μm) was employed. The CO2 laser pulses were synchronized to the IR-FEL macropulses. The width of the CO2 laser pulses was adjusted to 10 ms to avoid IRMPD by the CO2 laser alone. IRMPD spectra of CdH+CID in the 3000−3800 cm−1 energy range were recorded in the 7T FT-ICR mass spectrometer with 1 s irradiation time of the OPO laser and 10 ms of the CO2 laser. The IRMPD spectrum corresponds to the fragmentation efficiency R = −ln(Iparent/(Iparent + ∑Ifragment)) as a function of the laser wavenumber, where Iparent and Ifragment are intensities of parent and fragment ions, respectively. 2.2. Calculations. Exploration of the potential energy surface (PES) was performed with the advanced conformational search implemented in the MacroModel suite, a part of the Schrödinger package.76 The conformational search was followed by a full optimization at the DFT level of all the structures with energy below 20 kJ/mol. Structure optimization, energy, and vibration frequencies were calculated at the B3LYP level of theory using the 6-31++G(d,p) basis set. All the calculations were done with the Gaussian 09 package.77 The vibrational spectra were simulated by convoluting the scaled calculated harmonic frequencies by a Gaussian line shape (FWMH = 10 cm−1). Scaling factors of 0.98 in the 900−1700 cm−1 region and 0.96 in the 3000−3800 cm−1 range were applied to correct the frequencies for anharmonicity and basis set incompleteness. Vertical excitation energies were calculated at the cc2 level, using the resolution-of-the-identity (RI) approximation78 and the correlation-consistent triple-ζ TZVPP basis sets79 by means of the Turbomole V6.2 program package.80

3. RESULTS AND DISCUSSION 3.1. Collision-Induced Dissociation Spectra. The CID mass spectra of CdH+ produced in the three manners described above, namely, CdH+ESI, CdH+CID, and CdH+UVPD, are C


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Figure 3. Experimental IRMPD spectrum of (a) CdH+ESI, (b) CdH+CID, and (d) CdH+UVPD obtained by monitoring water loss. Calculated spectra for (c) CdH+alk and (e) CdH+arom. Closed(2)arom is in full line and CdH+fragment in dotted line. The scaling factor used is 0.98 for the low-frequencies region (800−1700 cm−1) and 0.96 for the high-frequencies region (3000−3800 cm−1).

Figure 4. Ground-state geometry of the most stable conformers of protonated cinchonidine. All the optimizations are performed at the B3LYP/631++G(d,p) level.

1585 cm−1, which is absent in the spectra of CdH+CID and CdH+ESI. This band is reminiscent of that observed at 1550 cm−1 in protonated quinoline and assigned to the Narom−H bend.81 The difference between CdH+UVPD and CdH+ESI is even more prominent in the hydride stretch region. CdH+UVPD and CdH+ESI both show an intense band at 3649 cm−1 with a bandwidth of 11 and 14 cm−1, respectively. This band can be safely assigned to the ν(OH) stretch. The spectrum of CdH+ESI shows a broad band at 3234 cm−1, attributed to the ν(Nalk−H) stretch, with the proton located on the alkaloid part. In contrast, the spectrum of CdH+UVPD displays a narrow and intense band at 3470 cm−1 that is not observed for CdH+ESI. This band is out of the expected range for the ν(Nalk−H) stretch and again suggests the aromatic nitrogen atom as the protonation site.21 The two features observed at 1585 and 3470 cm−1 in the absorption spectrum of CdH+UVPD suggest that the proton is

presented in Figure 2. The fragmentation patterns are identical for the three species, with loss of water as the major fragment (m/z 277). Most of the other fragments arise from sequential fragmentation, with loss of part of the alkaloid frame from the dehydrated species. It should be noted that, for an identical radio-frequency value, the fragmentation efficiency is much higher for CdH+UVPD than for CdH+ESI or CdH+CID. This observation indicates a lesser stability of CdH+UVPD. 3.2. IRMPD Spectra. Figure 3a,b,d shows the IRMPD spectra of CdH+ESI, CdH+CID, and CdH+UVPD in the 900−1700 cm−1 region as well as the 3000−3800 cm−1 region. The spectrum of CdH+CID is very similar to that of CdH+ESI, which shows unambiguously that the two molecules are identical. In what follows, we will therefore focus on the comparison between CdH+ESI and CdH+UVPD. The two spectra show little difference in the 900−1430 cm−1 region, but CdH+UVPD shows a distinct absorption band with a maximum at D


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Table 1. Gibbs Energy (at Room Temperature) of CdH+ Conformers Relative to the Most Stable Open(3) Form Calculated at the B3LYP/6-31++G(d,p) Level of Theory, and Calculated NH+ Distances γ-Open(10)

γ-Open(3)

γ-Closed(2)

γ-Closed(1)

CdH+alk

CdH+arom

CdH+alk

CdH+arom

CdH+alk

CdH+arom

CdH+alk

CdH+arom

CdH+fragment

0.46

7.51 1.015

0.00

2.10 1.016

0.68

1.89 1.015

0.68

1.45 1.015

2.17 1.015

−1

ΔG (kcal mol ) d(Narom···H+) (Å) d(Nalk···H+) (Å)

1.026

1.023

1.026

1.027

Table 2. Experimental and Scaled Calculated Vibrational Frequencies for the Most Stable Conformers of CdH+, Determined at the B3LYP/6-31++G** Level of Theory, and Band Assignmentsa experimental frequency (cm−1)

γ-Open(10)

γ-Open(3)

γ-Closed(2)

γ-Closed(1)

CdH+ESI /CdH+CID

CdH+UVPD

CdH+alk

CdH+arom

CdH+alk

CdH+arom

CdH+alk

CdH+arom

CdH+alk

CdH+arom

CdH+fragment

vibrational mode

3651

3651 3470

3666

3656 3437

3655

3680 3436

3662

3677 3437

3663

3679 3436

3676 3437 1635 1597 1411

1080 1057

ν(OH) ν(Narom−H) ν(Nalk−H) ν(CCarom) ν(CCarom)/ν(CNrom) β(NH) β(CH)/β(OH) β(CH)/β(OH) ν(CCaliph) /ν(C−OH) ν(CCaliph) /ν(C−OH)

3234

1395 1305 1267 1050 a

3275 1614B 1585 1395 1310 1274 1070

3323

1397

1634 1600 1409

1054

1051

3279

1417

1634 1597 1416

1092

1089

3279

1407

1635 1597 1383

1406

1635 1600 1416

1045

1081 1055

1044

1088 1057

Only the calculated frequencies with substantial oscillator strength (>20 km/mol) are given. BShoulder.

alkaloid. In the open forms the difference in Gibbs energy between CdH+arom and CdH+alk is large enough to preclude the existence of CdH+arom in normal operating conditions. In contrast, there is not much difference in energy between the closed forms, as inferred from Table 1. The difference in Gibbs energy between CdH+arom and CdH+alk is of the order of 1 kcal mol−1 in the closed forms. As inferred from Table 1 and Table S1, all the low-energy structures of CdH+arom are of closed nature. The Narom−H+ bond length is similar in all the conformers with the proton localized at Narom and is slightly shorter than the Nalk−H+ bond length in CdH+alk. As a consequence, the ν(Nalk−H) stretch is expected to have a lower frequency than the ν(Narom−H) stretch. CdH+fragment is of closed nature; however, it is less stable than γ-Closed(1)arom, which is the most stable of all the calculated CdH+arom structures and to which it is closely related. Its simulated spectrum is presented in Figure 3e, as well as that of γ-Closed(1)arom. A tentative assignment of the main IRMPD features of CdH+ESI and CdH+UVPD is proposed in Table 2 by comparing the experimental vibrational frequencies with those calculated for the IR active vibrational modes. The calculated spectra of the other CdH+arom conformers are shown in Figure S1 and Figure S2. a. Protonation at the Alkaloid Nitrogen. The calculations are in line with what has been previously published.66 In the hydride stretch region, the calculated spectra show two strong absorptions in the 3650−3680 and the 3240 cm−1 regions, attributed to the ν(OH) and ν(Nalk−H) stretches, respectively. No band appears in the 1600 cm−1 range, where the ν(CCarom) and ν(CNarom) are expected, in line with their very weak calculated oscillator strength. The band observed around 1400 cm−1 corresponds to β(NH) coupled to β(CH) bends whereas the broad massif around 1300 cm−1 is due to coupled β(OH) and β(CH) bending modes. These bands are experimentally much stronger than calculated because the laser power peaks in this range. Last, the ν(CC) and the ν(CO) stretches are

localized at the quinoline nitrogen in this species. Definitive assignment is proposed in the next section on the basis of DFT calculations. 3.3. Calculation Results. The four structures of CdH+ populated at room temperature have been previously described.61,66 They are all protonated at Nalk and will be denoted CdH+alk hereafter for the sake of clarity. Two of them are open, namely, γ-Open(3) and γ-Open(10), with the alkaloid extending far from the aromatic ring, the two others are closed forms, namely, γ-Closed(1) and γ-Closed(2), with the alkaloid folding over the aromatic ring. They are shown in Figure 4. The structure of CdH+UVPD is not the nascent form resulting from proton transfer in the excited state of the dimer followed by dissociation. Indeed, the time scale of the experiment, of the order of the seconds, allows CdH+UVPD to undergo collisions with helium and to relax.82 The calculation strategy consists therefore of searching for the most stable structures with the proton located at Narom, denoted CdH+arom hereafter. To this end, structures have been generated in the following way. First, the (Cd)2H+ dimer previously determined,66 which involves an Nalk−H+···Narom hydrogen bond, has been cut along the Nalk−H bond. The resulting fragment, denoted CdH+fragment in what follows, has been optimized. It is shown in Figure 4. Second, for each of the four CdH+alk structures populated at room temperature, the proton has been transferred to the aromatic nitrogen and the resulting CdH+arom structure has been fully optimized. The resulting structures are also shown in Figure 4. Last, full exploration of the PES has been performed. The lowenergy structures found this way are the previously mentioned CdH+fragment or the CdH+arom structures already found, γClosed(1) and γ-Closed(2), or α-Closed structures that give less satisfactory agreement with the experimental spectra. The latter structures are described in the Supporting Information. The Gibbs energies and NH bond lengths are reported in Table 1 and Table S1. The conformers protonated at the aromatic ring are higher in energy than those protonated at the E


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The Journal of Physical Chemistry A expected between ∼1050 and ∼1100 cm−1. Depending on the conformer, only one or several bands are active in this region; they correspond to the coupled ν(CC) and the ν(CO) motions. In both regions, the simulated spectrum of γClosed(1)alk gives the best agreement with the experimental spectrum of CdH+CID or CdH+ESI, in particular in the 1050− 1100 cm−1 region where only one strong bond is observed. We therefore conclude that γ-Closed(1)alk is the major species in our experimental conditions. It is also to be noted that no strong band is observed above 1500 cm−1 in the CdH+alk species. b. Protonation at the Aromatic Nitrogen. The calculated conformers with the proton on Narom also present two absorption bands in the hydride stretch region. The ν(OH) stretch appears in the same range as in CdH+alk, around 3660 cm−1. The frequency of the calculated ν(Narom−H) stretch is independent of the conformer and is located at 3436 ± 1 cm−1. The low-frequency region is characterized by numerous bands of weak intensity, assigned to coupled OH, NH, and CH bending or stretching modes. In this region, the ν(CCarom) stands out and appears strongly at ∼1600 cm−1. The strong increase in intensity relative to CdH+alk arises from a dramatic increase of the dipole in the aromatic ring, due to the charge. The spectra of γ-Closed forms or CdH+fragment agree well with the experimental spectrum of CdH+UVPD. The frequencies measured at 3651 and 3470 cm−1 are readily assigned to the ν(OH) and ν(NaromH) stretches whereas the band at 1585 cm−1 can be assigned to the ν(CCarom) and ν(CNarom) stretches. The low experimental intensity of these bands is related to a weaker laser power in this range. It may also be due to insufficient coupling between the optically excited mode and the vibrational manifold. Bands much weaker than calculated are indeed often observed in this range.83 This assignment confirms that protonation occurs at the aromatic ring nitrogen in CdH+UVPD. For energetic reasons and good correspondence with the experimental spectrum, we will assign CdH+UVPD to the most stable γ-Closed(1)arom structure. 3.4. Proposed Mechanism. UV excitation of the dimer results to proton transfer followed by dissociation of the complex. The assumption that proton transfer happens in the excited state is supported by the following two arguments. First, collision activation of the dissociation does not lead to proton transfer, whatever the collision energy. Indeed, CdH+CID shows exactly the same vibrational signature as CdH+ESI, which proves unambiguously that the two species are identical. On the contrary, it is to be noted that the CID fragments are identical for CdH+arom and CdH+alk, which is in good agreement with the mobile proton model proposed for CID.84 However, relative intensities of the fragments are different, which reflects differences in the potential energy surface reached before fragmentation. Second, the basicity of neutral quinoline derivatives is known to increase when the ππ* transition is excited. Although the most basic site of Cd in the electronic ground state is Nalk (pKA = 9.7 vs pKA = 5.7 for Narom), the pKA of Narom increases upon electronic excitation by 6 pK units in aqueous solution.37,85 One can therefore safely assume that proton transfer follows electronic excitation. The resulting structure dissociates either in the electronic excited state or in the ground state after internal conversion (IC). In either case, CdH+arom is produced. The calculated vertical S0−S1 transitions are located at 4.25 eV for the γ-Closed(1) form of CdH+alk and 2.64 eV for the γClosed(1) form of CdH+arom, with the zero of the scale located

at the ground state of CdH+alk, which shows that the process is energetically possible. The results obtained there allow proposing a complete reaction scheme after excitation of the protonated cinchonidine dimer, which can be excited on either its neutral or protonated moiety. Excitation of the protonated part results to proton transfer followed by cleavage of the C8−C9 bond, as evidenced before by probing the structure of the produced cation.21 As shown here, excitation of the neutral part results to proton transfer followed by the dissociation of the proton-transferred complex. Both mechanisms involve proton transfer from the alkaloid ring to the quinoline nitrogen. However, different excited states are involved in the two channels. Proton transfer followed by dimer dissociation probably involves the excitation of the π* state of the neutral and is related to ESPT observed in quinoline derivatives.43,46 In contrast, excitation of the protonated part results in H atom loss from Nalk···H+ with concomitant electron transfer. The latter mechanism probably involves crossing with a σ* state related to that already described for Cα−Cβ cleavage of protonated peptides.50,51 Therefore, it cannot be excluded that it requires the absorption of more than one UV photon to be efficient. It should be mentioned at this stage that multiple photon absorption is necessary for dissociating unsubstituted protonated quinoline; however, the process is completely different and involves fragmentation of the aromatic ring.35

4. CONCLUSION Protonated cinchonidine, produced in the ESI source (CdH+ESI), by CID of the dimer (CdH+CID), and by photodissociation of the dimer (CdH +UVPD ) has been structurally characterized in an ion trap by means of IRMPD vibrational spectroscopy coupled with quantum chemical calculations. CdH+CID resulting from the collision-induced dissociation of the protonated dimer is protonated at the alkaloid ring like CdH+ESI. In contrast, protonation at the aromatic ring nitrogen is observed for CdH+UVPD. This body of results suggests that protonation at Narom is not possible in the ground state under our experimental conditions and is possible only via proton transfer in the electronic excited state. This work allows proposing a complete reaction scheme for the photoreactivity of protonated cinchona alkaloids dimers. Excitation of the neutral part leads to ESPT in the ππ* state, followed by dissociation of the intermolecular bond. This process leads in f ine to CdH+arom and neutral Cd. Excitation of the protonated part involves a πσ* state and leads to coupled hydrogen and electron transfer accompanied by cleavage of the C8−C9 bond. Moreover, these experiments provide an original means of forming metastable molecules. Although photoinduced proton transfer has been used already for forming protonated species, it was limited to their canonical forms.53 The method presented here allows forming metastable exotic species. Their UV spectroscopy would be of great interest because the nπ* transition located on the alkaloid might perturb the ππ* located on the protonated quinoline, the spectroscopy of which has been recently determined in the gas phase.35 Confrontation of spectra recorded in low-temperature conditions with ab initio calculations would bring interesting information on these systems.12,24 F


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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.5b06506. Table of relative energies, figure of geometries, and simulated spectra for additional structures, simulated spectra of structures listed in Table 1 but not given in Figure 3 (PDF)

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AUTHOR INFORMATION

Corresponding Author

*A. Zehnacker-Rentien. E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The research described here is supported by Triangle de la physique contract (CHIRAUX UV-IR n°2013-0562T). This work is supported by a public grant from the “Laboratoire d’Excellence Physics Atom Light Mater” (LabEx PALM) overseen by the French National Research Agency (ANR) as part of the “Investissements d’Avenir” program (reference: ANR-10-LABX-0039). We thank Dr. J. M. Ortega and the CLIO team for technical assistance. We acknowledge the use of the computing facility cluster GMPCS of the LUMAT federation (FR LUMAT 2764). Computer time allowance by DI Univ. Paris-Sud is acknowledged.

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REFERENCES

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