Real-Time Probing of Chirality During a Chemical Reaction

Real-time probing of chirality during a chemical reaction

Denitsa Baykushevaa, Daniel Zindela, Vìt Svobodaa, Elias Bommelia, Manuel Ochsnera, Andres Tehlara, and Hans Jakob Wörnera,1

aLaboratory of Physical Chemistry, ETH Zürich, 8093, Zurich, Switzerland

This manuscript was compiled on October 29, 2019

Chiral molecules interact and react differently with other chiral ob- plosion imaging (CEI, (17, 18)), laser-induced mass spectrome- jects, depending on their handedness. Therefore, it is essential to try (19, 20), photoelectron circular dichroism (PECD, (21–25)), understand and ultimately control the evolution of molecular chiral- and high-harmonic generation (HHG) in elliptically polarized ity during chemical reactions. Although highly sophisticated tech- (26) and two-color laser fields (27). Time-resolved PECD (TR- niques for the controlled synthesis of chiral molecules have been PECD) has so far only been demonstrated in the single-photon- developed, the observation of chirality on the natural femtosecond ionization regime using laser pulses in the visible domain (28). time scale of a chemical reaction has so far remained out of reach in As a consequence, it has remained restricted to probing dy- the gas phase. Here, we demonstrate a general experimental tech- namics in highly excited states rather than photochemical nique, based on high-harmonic generation in tailored laser fields, reactions. The extension of TR-PECD to XUV and soft-X-ray and apply it to probe the time evolution of molecular chirality during radiation derived from high-harmonic (29) and XFEL (30, 31) the photodissociation of 2-iodobutane. These measurements show facilities currently represents an active research direction. a change in sign and a pronounced increase in the magnitude of the Here, we introduce an all-optical, ultrafast and nearly gen- chiral response over the first 100 fs, followed by its decay within less eral experimental technique for probing the time-dependent than 500 fs, revealing the photodissociation to achiral products. The chirality of molecules undergoing a photochemical reaction. observed time evolution is explained in terms of the variation of the This method combines the established sensitivity of HHG electric and magnetic transition-dipole moments between the lowest spectroscopy to photochemical dynamics (32–34) with the electronic states of the cation as a function of the reaction coordi- unique chiral sensitivity of HHG in two-color counter-rotating nate. These results open the path to investigations of the chirality of circularly-polarized (so-called ”bi-circular”) laser fields, which molecular reaction pathways, light-induced chirality in chemical pro- was theoretically predicted (35–37) and experimentally demon- cesses and the control of molecular chirality through tailored laser strated on unexcited molecules very recently (27, 38, 39). pulses. The key advantages of our pump-probe technique are its sensitivity to gas-phase samples, its temporal resolution and the background-free detection of the excited-state dynamics. We demonstrate the ability of the technique to follow in real he two enantiomers of a chiral molecule interact differ- time the evolution of molecular chirality along a photochem- Tently with chiral receptors and with chiral light. The ical reaction pathway. This development paves the way to former effect is the basis of chiral recognition, an essential detecting the chiral interactions that underlie enantio-specific mechanism of biomolecular function. The latter is the principle of optical techniques for detecting chirality. Although extensive control over molecular chirality has been achieved in enantio-selective synthesis of molecules (1–3), chiral sen- Significance Statement sitivity has been lacking from all femtosecondDRAFT time-resolved Chiral molecules interact and react differently, depending on probes of chemical reactions in the gas phase demonstrated to their handedness (left vs. right). This chiral recognition is the date. The main origin of this shortcoming is the weakness of basic principle governing most biomolecular interactions, such chiral light-matter interactions, which rely on magnetic-dipole, as the activity of drugs or our perception of scents. Inspite electric-quadrupole and higher-order interactions. For this rea- of this fundamental importance, a real-time (femtosecond) ob- son, circular dichroisms (CD) in absorption spectroscopies are servation of chirality during a chemical reaction has remained −6 −3 typically very weak effects in the range of 10 to 10 relative out of reach in the gas phase. In the present work, we report signal changes. Nevertheless, time-resolved circular dichroism this breakthrough with a seemingly unlikely technique: high-

arXiv:1906.10818v2 [physics.chem-ph] 27 Oct 2019 (TRCD) techniques have gained increasing attention over the harmonic generation (HHG) in tailored intense near-infrared last 15 years (4), and nowadays cover the IR (5, 6), visible (7), laser fields. Combining the powerful transient-grating technique and UV (8–11) spectral regions. The promise of extending with HHG in counter-rotating circularly-polarized laser fields, such measurements to the X-ray domain has recently been we follow the temporal evolution of molecular chirality during a predicted (12–14). Unfortunately, the inherent weakness of chemical reaction from the unexcited electronic ground state the optical CD effects and the related technical challenges through the transition-state region to the final achiral products. have so far limited TRCD measurements to the condensed

phase and to picosecond or longer time scales. D.B. and H.J.W. designed research; D.B. and A.T. performed research; D.B. analyzed data; D.B. and V.S. performed theoretical calculations; D.Z., E.B. and M.O. contributed new reagents/analytic The development of more sensitive methods, applicable tools; D.B. and H.J.W. wrote the manuscript. to isolated molecules in the gas phase has therefore received The authors declare no conﬂict of interest. considerable attention (15). Important developments include microwave three-wave-mixing spectroscopy (16), Coulomb ex- 1To whom correspondence should be addressed. E-mail: [email protected]

www.pnas.org/cgi/doi/10.1073/pnas.XXXXXXXXXX PNAS | October 29, 2019 | vol. XXX | no. XX | 1–8 chemical reactions. Building on the self-probing capabilities variation pattern is produced in the focal plane, and, as effi- of high-harmonic spectroscopy (40, 41), our technique also cient photoexcitation is restricted to the high-intensity regions, provides access to the attosecond electron dynamics (42) of this modulation translates into alternating planes of excited the underlying chiral response (27) and its dependence on and ground-state molecules. The TG is probed by a bi-circular the chemical reaction pathway. With the recent extensions of field consisting of the superposition of two circularly polarized high-harmonic spectroscopy to solids (43–45) and liquids (46), ∼40 fs pulses centered at 1800 and 900 nm with opposite he- our technique will rapidly become applicable to all phases of licities. The corresponding electric field describes a Lissajous matter. In the liquid phase, it will give access to the interac- figure resembling a clover leaf, as illustrated on the left-hand tions underlying chiral recognition. In the solid state, it might side of Fig.2. As the HHG radiation emitted from the individ- open new approaches to elucidate dynamics in chiral crystals, ual layers of the grating in the near field is characterized by which include skyrmions in chiral magnets, unconventional different amplitudes and phases, a diffraction pattern is formed pairing in chiral superconductors, as well as unique magneto- in the far field, leading to a background-free detection of the electric effects in chiral metals. Its all-optical nature paired excitation (s. Fig. S1). As revealed by the data presented in with its high degree of chiral discrimination will facilitate its the SI Appendix, the typically achieved diffraction efficiencies application to dense or highly-charged forms of matter. reach up to 7 − 8%. The experiment consisted in measuring the intensity of the Results diffracted and undiffracted high-harmonic emission as a function of the time delay between the excitation and probe pulses. The light-induced dissociation of 2-iodobutane (2 − C4H9I), The dynamics of the 2-iodobutane photodissociation were in- depicted in Fig.1, was selected as an illustrative chemical vestigated for pump-probe delays ∆t spanning the range from reaction. Photoexcitation of this molecule at 266 nm accesses -0.15 to 5 ps. The panel in the bottom right corner of Fig.2 ˜ 3 + the A-band and mainly populates the Q0 -state in a parallel shows the short-time evolution of signal in harmonic order transition, as revealed by magnetic circular-dichroism measure- 23 (of 1800 nm, ∼ 15.8 eV) recorded in racemic 2-iodobutane. 3 + ments (47). The repulsive potential-energy curves of the Q0 The orange curve represents the undiffracted intensity (Im=0), 3 1 and the two close-lying electronic states ( Q1 and Q1) are while the averaged diffracted (m = ±1) signals are shown in given in the Supplementary Information (SI) Appendix, Fig. dark green. Temporal overlap of the pump and probe pulses 3 + S3. Following excitation to the Q0 -state, the molecule dis- leads to high-order wave mixing (49), which appears spatially sociates into a 2-butyl radical and a spin-orbit-excited iodine separated from the other signals on the detector (see SI Ap- ∗ 2 atom (I , P1/2) on an ultrafast time scale. pendix, Fig. S1). This wave-mixing signal, averaged over its The breakage of the C-I bond also induces a major modifi- two components (wm = ±1) is shown as black line. It accu- cation of the chiral structure of the molecule. The main idea rately determines the characteristic cross-correlation time of of our work is to map out the temporal evolution of the molec- the experiment (≈ 45 fs). ular chirality as the laser-induced photodissociation takes its The temporal evolution of the undiffracted intensities is course. We thereby answer the following questions. Is the qualitatively similar for all harmonic orders, as is the time 2-butyl radical produced in a chiral or achiral state? How fast evolution of all observed diffracted intensities. We characterize do the signatures of the changing chirality evolve from the the photodissociation dynamics observed in each harmonic or- reactant to the product state? Which properties of molecular der by quantifying the exponential time scale of intensity build chirality is our method sensitive to? up in the diffracted signals τrise, defined by the phenomenolog- 3 + TheThe time experimental axis is mapped using setup Denitsa‘s is WP illustrated propagation calculation in Fig. on2 A.Q0 Astate. tran- ical kinetic expressions given in Eqs. (1-2) in the SI Appendix. sient grating (TG, (32, 33, 48)) is produced by crossing two The extracted values of τrise, averaged over multiple measure- linearly-polarized vertically-offset 266 nm pulses in a super- ments, are listed in the SI Appendix (s. Tab. I). Notably, the sonic expansion of gaseous 2-iodobutane. ADRAFT periodic intensity observed (averaged) dissociation time scale (τrise ≈ 370 fs) is

r(C-I) = 7.00 Å t = 137 fs r(C-I) = 2.154 Å r(C-I) = 2.50 Å r(C-I) = 2.75 Å r(C-I) = 3.25 Å t = 0 fs t = 10 fs t = 23 fs t = 38 fs

dissociation coordinate

Fig. 1. Illustration of the investigated photochemical reaction. An initially chiral molecule is photoexcited by a femtosecond laser pulse centered at 266 nm. The ensuing photodissociation reaction leads to a time-dependent change in the structure of the chiral center. The left-most panel displays the equilibrium geometry of (R)-2-iodobutane (s. SM for details). The structures in the other panels have been obtained by varying the C-I bond distance and relaxing all remaining degrees of freedom. The corresponding time delays have been taken from the wave packet calculations shown in Fig. S6.

2 | www.pnas.org/cgi/doi/10.1073/pnas.XXXXXXXXXX Baykusheva et al. gas jet HHG probe pulse far-field high-harmonic bicircular spectrum (1800 + 900 nm) H16 H19 H22 H25 XUV far-field pattern

m=+1

m=0 Δt pump photon energy pulses RS m=-1 (266 nm)

populations XUV near-field 0 r 1 emission

C4H9· + I·

C4H9I

C4H9· + I· Λ C4H9I

C4H9· + I·

excited unexcited x 1/20 molecules molecules

Fig. 2. Principle of bi-circular high-harmonic transient-grating spectroscopy. Two noncollinear pump beams are crossed under a small angle, creating an intensity grating which spatially modulates the molecular excitation. High-harmonic radiation is generated by a temporally delayed bi-circular field consisting of a 1800 nm pulse and its second harmonic centered at 900 nm. In the far-field, the radiation diffracted by the optical grating is spatially separated from the undiffracted light. The panel in the bottom right corner shows the time-dependent signals observed in 2-iodobutane after excitation at 266 nm followed by HHG driven by a bi-circular 1800+900 nm field observed in the undiffracted orders (orange curve, left-hand vertical axis) and averaged wm = ±1- (black) and m = ±1- (dark green) orders (left-hand axis) for harmonic 23 of 1800 nm (∼ 15.8 eV). The origin of the time-scale has been set to the maximum of the wave-mixing signal. longer than the estimations from wave-packet calculations (s. configurations (α ∈ [35◦ − 55◦] resp. α ∈ [125◦ − 145◦]): Sec. IV in the SI Appendix) or extrapolations from previous studies (s. discussion in Ref. (50)). This observation is in αmax ± Z line with the conclusions from previous TG-HHG studies on CD (nω) = CD(nω, α)dα, [1] the photodissociation dynamics of Br2 (51) and other alkyl αmin halides employing linearly polarized driving fields (52). We now turn to the characterization of the time-dependent whereby the superscript ± specifies the two possible helicity chirality during the photodissociation. Enantiomerically- combinations of the ω and 2ω laser fields. This procedure enriched samples (ee ∼ 60−65%) of (R)- and (S)-2-iodobutane minimizes the asymmetries resulting from imperfections of the were synthesized in house as described in the SI Appendix optical components and the optical path misalignments and DRAFTexpresses the CD as a function of the photon energy only. (Section II). The chirality-sensitive measurements were performed by monitoring the signal of the undiffracted emission Figure3 shows the high-harmonic signal in harmonic order (Im=0) as the ellipticity of the ω and 2ω laser fields constitut- 19 (H19) in terms of the undiffracted-signal intensities emitted ing the bi-circular field is varied by rotating the main axis of from the individual enantiomeric samples ((R) and (S)), as blue the achromatic quarter-waveplate (QWP) from α = 30◦ to and red curves in the upper row. The differential ellipticity- α = 150◦. In this manner, the polarization of the ω and 2ω resolved CDs are shown in the lower row. Since the two laser fields is changed from circular via elliptical to linear and employed samples have similar enantiomeric excesses of 60- then back to circular again. At both α = 45◦ and α = 135◦, 65 %, the reported CDs are lower than those of the enantiopure the two pulses combine into a bicircular field, but with oppo- samples by approximately this amount. The antisymmetry site helicities. These two helicities interact differently with of the green curves in Fig.3 shows that a reversal of the the chiral molecules, resulting in a CD effect in the intensity rotation direction of the driving fields has the same effect as of the emitted high-harmonic radiation. Expressions (III- changing the handedness of the molecular sample, eliminating IV) of the SI Appendix outline the procedure for extracting the possibility of artefactual contributions. The temporal ± the frequency- and ellipticity-dependent circular dichroism evolution of CD (nω) for all harmonic orders is compactly CD(nω, α) from the normalized HHG intensities IR/S(nω) presented in Fig.4, where the individual panels correspond to recorded from each enantiomer, where nω denotes the fre- the points of the pump-probe delay grid. quency of the nth-harmonic of the fundamental frequency ω. The CD was first measured in the absence of the pump We further define an ellipticity-averaged quantitative mea- pulses to characterize the chiral response of the unexcited sure for the observed CD by averaging the ellipticity-resolved molecules. The obtained CD is on the order of 2% at H19 CD(nω, α) in the region close to the two opposite bi-circular (see Fig.3, left panel) and across the whole range of harmonic

Baykusheva et al. PNAS | October 29, 2019 | vol. XXX | no. XX | 3 H19

Fig. 3. Upper row: Normalized responses of the (R)- (blue) and the (S)- (red) enantiomers of 2-iodobutane at different pump-probe delays as a function of ellipticity expressed in terms of the QWP rotation angle α. The signals correspond to harmonic 19 of 1800 nm, or ∼ 13.1 eV. Bottom row: Ellipticity-dependent circular dichroism at harmonic 19 for each time step. orders (see Fig.4a). These values are notably smaller than in Discussion the case of methyloxirane (27) and limonene (39). Although In this section, we discuss the experimental observations and the CDs are somewhat diminished by the limited enantiopurity provide a qualitative interpretation. There are basically two of our sample (see above), the CDs scale approximately linearly possible mechanisms for explaining a pump-induced variation with the enantiomeric excess, such that the smallness of the of the CD. First, we discuss the role of the rotational dynamics CD must be a property of 2-iodobutane in its electronic ground induced by photoexcitation, and then proceed with an analysis state. of the transient CD changes associated with the modifications of the chiral structure of the molecule. In the presence of the pump pulses, the CD changes sign Resonant one-photon-excitation leads to the selective exci- and significantly increases in magnitude (Fig.3) across all tation of a sub-ensemble of molecules that have their transition- detected high-harmonic orders (H10-H31, Fig.4b). At and dipole moments aligned along the polarization direction of after time zero (T0), the maximal CD values in H19 amount the pump pulse(s). This effect leads to a partial alignment ± to 6 − 7%. The averaged |CD (19ω)| valueDRAFT amounts to ∼ of the excited molecules that decays on the picosecond time scale. Since CD effects in bi-circular HHG strongly depend on 2% at T0, increases to ∼ 2.5% after 100 fs, and eventually reaches a maximum of 2.7% at 250 fs. After 500 fs have the orientation of the molecule relative to the laser field (36), elapsed, there is essentially no detectable chiral response left partial alignment can enhance the CDs and the subsequent and the same is true for the subsequent points on the time rotational dephasing could explain their decay. Therefore, we grid. Other harmonic orders exhibit a qualitatively similar have performed detailed calculations on the time dependence behaviour, although there are differences concerning the time of the alignment of 2-iodobutane caused by the pump pulses. delay maximizing the chiral response (see, for instance, H10 These calculations, that are summarized in the SI Appendix and H13 in Fig.4, for which |CD| maximize at ∆t = 250 fs (section VI and Fig. S8), show that for typical expected ro- and 100 fs, respectively). tational temperatures of 5-30 K in our supersonic expansion, the rotational anisotropy decays on a time scale of 11-5 ps. Since these time scales are much longer than the observed CD The results summarized in Fig.4 lead to the following dynamics, we can exclude rotational dynamics as the origin of main conclusions: i) a strong chiroptical response appears our observations. during the excitation by the short 266 nm pulse, which is Therefore, the observed CD dynamics are most likely to be opposite in sign to that of the unexcited molecules; ii) the caused by the structural modification of the chiral center as induced chiral response persists up to & 250 fs, after which it the reaction progresses. In the following, we discuss a theoret- decays, signalling the formation of an achiral product state; ical model that captures the essential features of the observed iii) the chiral response observed below the ionization energy chiral dynamics. Our model builds on previous theoretical of 2-iodobutane (9.13 eV) displays a strong dependence on the analysis of bi-circular HHG from chiral molecules (26, 27, 53), emitted photon energy. which has linked the induced chiral response with the interplay

4 | www.pnas.org/cgi/doi/10.1073/pnas.XXXXXXXXXX Baykusheva et al. a) d)

b) e)

c) f)

Fig. 4. Ellipticity-averaged circular dichroism observed in 2-iodobutane as a function of the photon energy. The data in each panel is recorded at a different value of the pump-probe delay ∆t.

of electric- and magnetic-dipole transitions occurring during vertical ionization potentials Ip of ≈ 9.13 eV and ≈ 9.68 eV) + the propagation of the electron in the continuum. If several va- and the first excited (A˜ , Ip ≈ 11.08 eV) states (54, 55). Ne- lence shells lie sufficiently close in energy (. 2 eV), strong-field glecting the spin-orbit interaction in the cationic states, this ionization can leave the cation in a coherent superposition of gives rise to in total four channels contributing to the HHG several electronic states. During propagation of the electron in process. Two channels are formed by strong-field ionization the continuum, laser-induced couplings between these states to the X˜ + or A˜+ state of the cation and photorecombination lead to the emergence of HHG ”cross-channels”, whereby the of the continuum electron with the same state. These chan- returning electron recombines with the cation in a state that nels are accordingly labeled XX or AA. In addition, there is different from the one created during ionization. Circu- are two ”cross channels” (XA, AX). Under these premises, lar dichroism emerges through the participation of the weak the treatment of the laser-induced dynamics reduces to a sys- magnetic-field component of the driving laser pulses in the tem of two coupled ordinary differential equations that has a laser-induced dynamics, whereby the chiral sensitivity is exclu- straightforward solution, as presented in Section V of the SI sively conveyed by the cross channels mentioned above. Our Appendix. After integrating Eq. (5) of the SI Appendix over DRAFTΩ previous analysis has shown that although the corresponding the duration τ of a given electron trajectory (typical values changes in the induced dynamics are extremely small (10−4 ranging from 1.4 to 1.8 fs for our experimental conditions), the level in the electron-hole density), a substantial CD (up to calculated coefficients {cIJ (∆t)} (with {I,J} ∈ {X,A}) for 13% in the case of methyloxirane) can result (27). each channel are used to obtain the frequency-domain HHG Limiting our analysis of the A˜-band dynamics to photoex- dipole response (at a photon energy Ω) as a function of the 3 + citation via the Q0 -state as explained above, we first extract pump-probe delay (26): the evolution of the expectation value of the C-I-bond distance (3/2) 2π Ω (hrCIi(∆t)) as a function of the pump-probe delay ∆t from a X I iS(Ω,τ IJ ) J d(Ω, ∆t) = cIJ (∆t)aion(Ω, ∆t) e arec(∆t), wavepacket propagation on the corresponding one-dimensional iτ Ω (∆t) IJ IJ potential-energy curve (see SI Appendix, Sec. IV). Within a [2] classical-trajectory treatment, the bond length is bijectively Ω mapped onto the pump-probe delay, which allows us to express where S(Ω, τ IJ ) corresponds to the semi-classical action. all relevant potential-energy curves and coordinate-dependent Here, we are primarily interested in rationalizing the tem- transition moments as a function of the pump-probe delay. poral profile of the chiral response as a complete quantita- Detailed information on the quantum-chemistry calculations tive description of the HHG process for many-electron sys- is given in the SI Appendix (Sec. III). tems is still out of reach. Therefore, we set the ionization Considering the pulse intensities employed in the experi- (aion(Ω, ∆t)) and the recombination (arec(Ω, ∆t)) matrix ele- 13 2 ment (. 5 × 10 W/cm and wavelengths of 1800/900 nm), ments in Eq. (2) to unity, which amounts to neglecting their 3 + strong-field ionization from the Q0 -state populates mainly dependence on the molecular-frame ionization/recombination the ground (X˜ +, split into two spin-orbit components with directions. With these approximations, the chiral response is

Baykusheva et al. PNAS | October 29, 2019 | vol. XXX | no. XX | 5 the chiral response and its vanishing for long delays reflect the progressive loss of chirality during the C-I bond breaking process. We have carried out a detailed comparison of the predictions of our theoretical model including or neglecting the planarization of the 2-butyl radical (s. section III B in the SI Appendix). This comparison has shown that the geometric relaxation of the 2-butyl radical does not qualitatively change the predicted CD dynamics, which are therefore dominated by the detachment of the iodine atom from the molecular backbone. This conclusion is further supported by our analysis of the time scale of the interconversion dynamics following the initial formation of the chiral enantiomeric 2-butyl radical conformer. The calculations presented in Section VIII of the SI Appendix corroborate the fact that in the absence of coherent stereomutation, rapid racemization of the initially formed Fig. 5. Time-dependent CD signal, evaluated according to Eq. (3) at photon energies chiral 2-butyl radical will take place. corresponding to H16, H20, and H31 of 1800 nm. The instantaneous direction of Turning to the remaining discrepancies, we note that the the ionizing bi-circular field is set parallel to the C-I-bond axis. The signal is averaged measured CDs appear to decay more slowly than the calculated over the azimuthal angle associated with this axis. ones. Similarly, we noted above that the (non-chiral) signals suggest a longer dissociation time (340 fs) than predicted by entirely encoded in the variation of the electric- and magnetic- our one-dimensional wave-packet calculations. The consis- dipole matrix elements within the sub-cycle temporal interval tent deviation of these two classes of observables from their between ionization and recombination. The time-dependent calculated counterparts most likely originate from neglecting circular dichroism CD(Ω, ∆t) is estimated by calculating the the structure-dependent ionization and recombination matrix spectral HHG intensity S˜(Ω; ∆t) ∝ |d(Ω, ∆t)|2 for a (R)- elements, because all other quantities have been accurately 2-iodobutane molecule with its C-I-bond-axis aligned along incorporated into our theoretical model. the instantaneous electric-field direction as well as for its (S)- enantiomer and subsequently forming the differential response: Conclusion S˜(R)(Ω, ∆t) − S˜(S)(Ω, ∆t) In this article, we have introduced a new technique for detect- CD(Ω, ∆t) = 2 . [3] max S˜(R)(Ω, ∆t) + S˜(S)(Ω, ∆t) ing time-dependent chirality during a chemical reaction. We have applied this technique to study the chirality changes oc- Figure5 shows the CD obtained with the above relation for curring in the course of the photodissociaton of 2-iodobutane. three selected harmonic orders (H16, H20 and H31) as a With the aid of a conceptually simple theoretical treatment function of the pump-probe delay. Since our model does not based on high-level ab-initio quantum-chemical calculations, contain the structure-sensitive contributions from the ioniza- we have been able to correlate the time evolution of the CD tion and the recombination steps, a quantitative prediction of signal with the coordinate dependence of the electric- and ± the magnitude of CD (Ω) is not expected. magnetic-dipole matrix elements that encode the chiral re- However, a special feature of our HHG scheme of probing sponse in the HHG process. chiral dynamics is the fact that the chiroptical response en- This technique is sufficiently sensitive to be applicable to tirely originates from the second, continuum propagation step, the gas phase, but is equally applicable to liquids (46) and in which the electron can be treated as decoupledDRAFT from the solids (43) in future experiments. Its relatively large CD parent ion in good approximation. Therefore, the time depen- effects, comparable in magnitude to PECD, combined with its dence of the chiral response will mainly be dictated by the all-optical nature make it a powerful chiral-sensitive method variation of the chiral structure of the probed molecule, which for detecting ultrafast changes in molecular chirality. The is encoded in the geometry-dependent electric and magnetic ability to probe chiral photochemical processes on such time dipole-transition-matrix elements of the cation. In our work, scales opens up a variety of possibilities for investigating chiral- the latter are calculated with high accuracy using modern recognition phenomena, such as the processes that determine quantum-chemistry methods (SI Appendix, Sec. V). the outcome of enantioselective chemical reactions. Paired Our results predict a rapid increase of the CD signal at early with recent developments in condensed-phase high-harmonic time delays, followed by one relatively sharp local maximum spectroscopy, our technique will rapidly be applied to all phases around 50 fs and a broad shoulder feature around 100 fs, and of matter, where it will unlock the study of a range of chiral then monotonous decay by 2-3 orders of magnitude within phenomena on ultrashort time scales. ∼ 250 − 300 fs. The overall dynamics of the calculated CDs therefore capture the main features of the experimental results, Methods which show local maxima around 100 fs and a subsequent decay. Moreover, the results in Fig.5 predict a pronounced Details on the experimental setup and data evaluation are spectral dependence of the time-dependent chiral response, given in SI Appendix I. The synthesis of enantiomerically- which is also present in the experimental results shown in enriched 2-iodobutane is described in SI Appendix II. The Fig.4. This comparison shows that our simple model captures theoretical work including the quantum-chemical ab-initio the salient features of the measured chiral dynamics. Our calculations, the quantum-dynamical calculations and the CD calculations further allow us to conclude that the decay of calculations are given in the SI Appendices III-VIII.

6 | www.pnas.org/cgi/doi/10.1073/pnas.XXXXXXXXXX Baykusheva et al. Data Availability B. Fabre, S. Patchkovskii, O. Smirnova, Y. Mairesse, and V. R. Bhardwaj, “Probing molecular chirality on a sub-femtosecond timescale,” Nature Physics 11, 654–658 (2015) The data presented in this article is available from the corre- . sponding author upon request. 27. Denitsa Baykusheva and Hans Jakob Wörner, “Chiral discrimination through bielliptical high- harmonic spectroscopy,” Phys. Rev. X 8, 031060 (2018) . 28. Antoine Comby, Samuel Beaulieu, Martial Boggio-Pasqua, Dominique Descamps, Francois ACKNOWLEDGMENTS. DB thanks Prof. Frank Neese for help- Légaré, Laurent Nahon, Stéphane Petit, Bernard Pons, Baptiste Fabre, Yann Mairesse, and ful discussions regarding the calculation of the distance-dependent Valérie Blanchet, “Relaxation Dynamics in Photoexcited Chiral Molecules Studied by Time- magnetic dipole moments. We thank ETH Zurich for the alloca- Resolved Photoelectron Circular Dichroism: Toward Chiral Femtochemistry,” Journal of Phys- tion of computational resources on the EULER cluster. We thank ical Chemistry Letters 7, 4514–4519 (2016) Prof. Ivan Powis (Nottingham) for suggesting to study 2-iodobutane . in this work. This work was supported by the Swiss National Science 29. V. Svoboda et al. (2019) (in preparation). Foundation under project 200021_172946 and the NCCR-MUST. 30. Faccialà D, et al. (2019) Time-Resolved Photoelectron Circular Dichroism of Fenchone at FERMI in XXXIst International Conference on Photonic, Electronic, and Atomic Collisions (ICPEAC). 1. Doug E Frantz, Roger Fässler, and Erick M Carreira, “Facile enantioselective synthesis of 31. Schmidt P, et al. (2019) Ultrafast Structural Changes in Chiral Molecules Measured with Free- propargylic alcohols by direct addition of terminal alkynes to aldehydes,” Journal of the Amer- Electron Lasers in XXXIst International Conference on Photonic, Electronic, and Atomic Col- ican Chemical Society 122, 1806–1807 (2000). lisions (ICPEAC). (Deauville), pp. TU–041. 2. Tehshik P Yoon and Eric N Jacobsen, “Privileged chiral catalysts,” Science 299, 1691–1693 32. H. J. Wörner, J. B. Bertrand, D. V. Kartashov, P. B. Corkum, and D. M. Villeneuve, “Following (2003). a chemical reaction using high-harmonic interferometry,” Nature 466, 604–607 (2010). 3. Kyle W Quasdorf and Larry E Overman, “Catalytic enantioselective synthesis of quaternary 33. H. J. Wörner, J. B. Bertrand, B. Fabre, J. Higuet, H. Ruf, A. Dubrouil, S. Patchkovskii, M. Span- carbon stereocentres,” Nature 516, 181 (2014). ner, Y. Mairesse, V. Blanchet, E Mével, E. Constant, P. B. Corkum, and D. M. Villeneuve, 4. Julia Meyer-Ilse, Denis Akimov, and Benjamin Dietzek, “Recent advances in ultrafast time- “Conical intersection dynamics in no probed by homodyne high-harmonic spectroscopy,” resolved chirality measurements: Perspective and outlook,” Laser and Photonics Reviews 7, 2 Science 334, 208–212 (2011). 495–505 (2013). 34. P. M. Kraus, Y. Arasaki, J. B. Bertrand, S. Patchkovskii, P. B. Corkum, D. M. Villeneuve, 5. Mathias Bonmarin and Jan Helbing, “A picosecond time-resolved vibrational circular dichro- K. Takatsuka, and H. J. Wörner, “Time-resolved high-harmonic spectroscopy of nonadiabatic ism spectrometer,” Optics Letters 33, 2086–2088 (2008). dynamics in no ,” Phys. Rev. A 85, 043409 (2012). 6. Hanju Rhee, Young-Gun June, Jang-Soo Lee, Kyung-Koo Lee, Jeong-Hyon Ha, Zee Hwan 2 35. Olga Smirnova, Yann Mairesse, and Serguei Patchkovskii, “Opportunities for chiral discrimi- Kim, Seung-Joon Jeon, and Minhaeng Cho, “Femtosecond characterization of vibrational nation using high harmonic generation in tailored laser fields,” Journal of Physics B: Atomic, optical activity of chiral molecules.” Nature 458, 310–313 (2009). Molecular and Optical Physics 48, 234005 (2015). 7. Claire Niezborala and François Hache, “Measuring the dynamics of circular dichroism in a 36. David Ayuso, Piero Decleva, Serguei Patchkovskii, and Olga Smirnova, “Chiral dichroism pump-probe experiment with a Babinet-Soleil Compensator,” Journal of the Optical Society in bi-elliptical high-order harmonic generation,” Journal of Physics B: Atomic Molecular and of America B 23, 2418–2424 (2006). Optical Physics 51, 06LT01 (2018). 8. Darius Abramavicius and Shaul Mukamel, “Time-domain chirally-sensitive three-pulse coher- 37. David Ayuso, Piero Decleva, Serguei Patchkovskii, and Olga Smirnova, “Strong-field con- ent probes of vibrational excitons in proteins,” Chemical Physics 318, 50–70 (2005). trol and enhancement of chiral response in bi-elliptical high-order harmonic generation: an 9. François Hache, Mai-Thu Khuc, Johanna Brazard, Pascal Plaza, Monique M Martin, Giovanni analytical model,” Journal of Physics B: Atomic, Molecular and Optical Physics 51, 124002 Checcucci, and Francesco Lenci, “Picosecond transient circular dichroism of the photore- (2018). ceptor protein of the light-adapted form of Blepharisma japonicum,” Chemical Physics Letters 38. Avner Fleischer, Eli Bordo, Ofer Kfir, Gil Ilan, Pavel Sidorenko, and Oren Cohen, “High Har- 483, 133–137 (2009). monic Generation Polarization States: Circular, Linear and Foucault-Fan,” in 6th International 10. Julia Meyer-Ilse, Denis Akimov, and Benjamin Dietzek, “Ultrafast circular dichroism study Conference on Attosecond Physics (2017). of the ring opening of 7-dehydrocholesterol,” The Journal of Physical Chemistry Letters 3, 39. Yoichi Harada, Eisuke Haraguchi, Keisuke Kaneshima, and Taro Sekikawa, “Circular dichro- 182–185 (2012). ism in high-order harmonic generation from chiral molecules,” Physical Review A 98, 021401 11. Malte Oppermann, Benjamin Bauer, Thomas Rossi, Francesco Zinna, Jan Helbing, Jérôme (2018). Lacour, and Majed Chergui, “Ultrafast broadband circular dichroism in the deep ultraviolet,” 40. S. Baker, J. S. Robinson, C. A. Haworth, H. Teng, R. A. Smith, C. C. Chirila, M. Lein, J. W. G. Optica 6, 56–60 (2019). Tisch, and J. P. Marangos, “Probing proton dynamics in molecules on an attosecond time 12. Jérémy R Rouxel, Markus Kowalewski, and Shaul Mukamel, “Photoinduced molecular chiral- scale,” Science 312, 424 (2006). ity probed by ultrafast resonant x-ray spectroscopy,” Structural Dynamics 4, 044006 (2017). 41. Olga Smirnova, Serguei Patchkovskii, Yann Mairesse, Nirit Dudovich, David Villeneuve, Paul 13. Yu Zhang, Jérémy R Rouxel, Jochen Autschbach, Niranjan Govind, and Shaul Mukamel, “X- Corkum, and Misha Yu. Ivanov, “Attosecond circular dichroism spectroscopy of polyatomic ray circular dichroism signals: a unique probe of local molecular chirality,” Chemical science molecules,” Phys. Rev. Lett. 102, 063601–4 (2009). 8, 5969–5978 (2017). 42. P. M. Kraus, O. I. Tolstikhin, D. Baykusheva, A. Rupenyan, J. Schneider, C. Z. Bisgaard, 14. Jérémy R Rouxel, Yu Zhang, and Shaul Mukamel, “X-ray raman optical activity of chiral T. Morishita, F. Jensen, L. B. Madsen, and H. J. Wörner, “Observation of laser-induced molecules,” Chemical science 10, 898–908 (2019). electronic structure in oriented polyatomic molecules,” Nat. Comm. 6, 7039 (2015). 15. Martin Quack, “Structure and dynamics of chiral molecules,” Angewandte Chemie Interna- 43. Shambhu Ghimire, Anthony D DiChiara, Emily Sistrunk, Pierre Agostini, Louis F DiMauro, tional Edition in English 28, 571–586 (1989). and David A Reis, “Observation of high-order harmonic generation in a bulk crystal,” Nature 16. David Patterson, Melanie Schnell, and John M Doyle, “Enantiomer-specific detection of chiral physics 7, 138 (2011). molecules via microwave spectroscopy.” Nature 497, 475–7 (2013). 44. T. T. Luu, M. Garg, S. Yu. Kruchinin, A. Moulet, M. Th. Hassan, and E. Goulielmakis, “Extreme 17. P Herwig, K Zawatzky, M Grieser, O Heber, B Jordon-Thaden, C Krantz, O Novotny, R Rep- DRAFTultraviolet high-harmonic spectroscopy of solids,” Nature 521, 498–502 (2015). now, V Schurig, D Schwalm, Z Vager, A Wolf, O Trapp, and H Kreckel, “Imaging the Absolute 45. G. Vampa, T. J. Hammond, N. Thire, B. E. Schmidt, F. Legare, C. R. McDonald, T. Brabec, Configuration of a Chiral Epoxide in the Gas Phase,” Science 342, 1084–1086 (2013). and P. B. Corkum, “Linking high harmonics from gases and solids,” Nature 522, 462–464 18. M. Pitzer, M. Kunitski, A. S. Johnson, T. Jahnke, H. Sann, F. Sturm, L. P. H. Schmidt, (2015). H. Schmidt-Böcking, R. Dörner, J. Stohner, J. Kiedrowski, M. Reggelin, S. Marquardt, 46. Tran Trung Luu, Zhong Yin, Arohi Jain, Thomas Gaumnitz, Yoann Pertot, Jun Ma, and A. Schiesser, R. Berger, and M. S. Schöffler, “Direct Determination of Absolute Molecular Hans Jakob Wörner, “Extreme-ultraviolet high-harmonic generation in liquids,” Nature Com- Stereochemistry in Gas Phase by Coulomb Explosion Imaging,” Science 341, 1096–1100 munications 9, 3723 (2018). (2013). 47. Aharon Gedanken, “The Magnetic Circular Dichroism of the A Band in CF I, C H I and 19. R. Li, R. Sullivan, W. Al-Basheer, R. M. Pagni, and R. N. Compton, “Linear and nonlinear cir- 3 2 5 t-BuI,” Chem. Phys. Lett. 137, 462–466 (1987). cular dichroism of R-(+)-3-methylcyclopentanone,” Journal of Chemical Physics 125, 144304 48. Y. Mairesse, D. Zeidler, N. Dudovich, M. Spanner, J. Levesque, D. M. Villeneuve, and P. B. (2006). Corkum, “High-order harmonic transient grating spectroscopy in a molecular jet,” Phys. Rev. 20. Alexander Bornschlegl, Christoph Logé, and Ulrich Boesl, “Investigation of CD effects in Lett. 100, 143903 (2008). the multi photon ionisation of R-(+)-3-methylcyclopentanone,” Chemical Physics Letters 447, 49. J. B. Bertrand, H. J. Wörner, H.-C. Bandulet, É. Bisson, M. Spanner, J.-C. Kieffer, D. M. 187–191 (2007). Villeneuve, and P. B. Corkum, “Ultrahigh-order wave mixing in noncollinear high harmonic 21. Burke Ritchie, “Theory of the angular distribution of photoelectrons ejected from optically generation,” Phys. Rev. Lett. 106, 023001 (2011). active molecules and molecular negative ions,” Physical Review A 13, 1411–1415 (1975). 50. María E. Corrales, Vincent Loriot, Garikoitz Balerdi, Jesús González-Vázquez, Rebeca 22. N. Böwering, T. Lischke, B. Schmidtke, N. Müller, T. Khalil, and U. Heinzmann, “Asymmetry in de Nalda, Luis Bañares, and Ahmed H. Zewail, “Structural dynamics effects on the ultra- photoelectron emission from chiral molecules induced by circularly polarized light,” Physical fast chemical bond cleavage of a photodissociation reaction,” Physical Chemistry Chemical Review Letters 86, 1187–1190 (2001). Physics 16, 8812 (2014). 23. Ivan Powis, “Photoelectron Circular Dichroism in Gas Phase Chiral Molecules,” Advances in 51. H. J. Wörner, J. B. Bertrand, D. V. Kartashov, P. B. Corkum, and D. M. Villeneuve, “Following Chemical Physics 138, 267–329 (2008) a chemical reaction using high-harmonic interferometry,” Nature 466, 604–607 (2010). . 52. A. Tehlar and H. J. Wörner, “Time-resolved high-harmonic spectroscopy of the photodissoci- 24. Ferré A, et al. (2014) A table-top ultrashort light source in the extreme ultraviolet for circular ation of CH I and CF I,” Molecular Physics 111, 2057–2067 (2013). dichroism experiments. Nature Photonics 9(2):93–98. 3 3 53. Olga Smirnova, Yann Mairesse, and Serguei Patchkovskii, “Opportunities for chiral discrimi- 25. Beaulieu S, et al. (2016) Universality of photoelectron circular dichroism in the photoionization nation using high harmonic generation in tailored laser fields,” Journal of Physics B: Atomic, of chiral molecules. New Journal of Physics 18(10). Molecular and Optical Physics 48, 234005 (2015), arXiv:1508.02890. 26. R. Cireasa, A. E. Boguslavskiy, B. Pons, M. C.H. H Wong, D. Descamps, S. Petit, H. Ruf, 54. R. G. Dromey and J. B. Peel, “Photoelectron spectroscopic correlation of the molecular or- N. Thiré, A. Ferré, J. Suarez, J. Higuet, B. E. Schmidt, A. F. Alharbi, F. Légaré, V. Blanchet,

Baykusheva et al. PNAS | October 29, 2019 | vol. XXX | no. XX | 7 bitals of the alkanes and alkyl iodides,” Journal of Molecular Structure 23, 53–64 (1974). 55. Kimura K., S. Katsumata, Y Achiba, T Yamazaki, and S Iwata, Handbook of HeI Photo- electron Spectra of Findamental Organic Molecules (Japan Scientiﬁc Society Press, Tokyo, 1981) .

DRAFT

8 | www.pnas.org/cgi/doi/10.1073/pnas.XXXXXXXXXX Baykusheva et al.