Real-Time Probing of Chirality During a Chemical Reaction

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Downloaded by guest on September 30, 2021 www.pnas.org/cgi/doi/10.1073/pnas.1907189116 a W Jakob Hans and Baykusheva Denitsa reaction a chemical during chirality of probing Real-time ial ocrual oaie w-oo ae ed 2) Whereas (27). fields ellip- laser and two-color polarized generation (26) circularly one-color to high-harmonic polarized tically photo- elliptically and 20), weakly (21–25)], in (19, (HHG) [PECD spectrometry mass CD laser-induced electron 18), imag- (17, explosion ing Coulomb (16), microwave spectroscopy include three-wave-mixing developments Important consider- (15). received attention therefore has able phase, gas the in molecules lated scales. time longer the or to picosecond to measurements and TRCD phase limited condensed tech- far X-ray related so the have the and challenges effects nical CD to optical the the Unfortunately, measurements of (12–14). weakness predicted inherent such regions. been recently extending spectral has (8–11) domain of infrared (UV) the ultraviolet promise cover and nowadays The (7), and visible (4) 6), y increasing 15 (5, gained last have the over techniques attention in (TRCD) effects CD weak time-resolved very (CDs) of typically dichroisms range are the circular spectroscopies reason, absorption this this in For of higher- interactions. and origin electric-quadrupole, order interactions, main magnetic-dipole, light–matter on The chiral rely of date. which weakness to the in is demonstrated reactions shortcoming phase chemical of gas probes the from time-resolved lacking been syn- femtosecond has enantio-selective sensitivity all chiral in (1–3), over molecules achieved of control been of thesis extensive has mechanism Although chirality essential chirality. molecular tech- optical detecting an of for principle recognition, the niques is chiral latter The of function. biomolecular basis the is T chirality ultrafast chirality tailored through chirality pulses. molecular of laser of chirality control chemical the the in and of chirality processes, investigations light-induced to pathways, path coordinate. molecular-reaction the reaction the and open of elec- electric function results a lowest the These as cation of the the of variation between states the tronic moments revealing of transition-dipole fs, terms 500 in magnetic than explained evo- first time less is observed the The within lution over products. decay achiral response to its photodissociation chiral pronounced by the the a followed of and fs, magnitude sign 100 the in change in of a increase evolution show time 2-iodobutane. measurements the of probe These photodissociation to the general it during chirality a apply in molecular demonstrate and generation fields, we high-harmonic remained laser Here, on far tailored phase. based so gas technique, has the reaction experimental in chemical reach a fem- of natural of out the scale on have time chirality molecules of tosecond chiral observation of the developed, synthesis been controlled the sophisticated for molecular highly techniques of Although evolution reactions. chemical the during control chirality essential ultimately chiral is and it other understand Therefore, 2019) with to 29, handedness. April their differently review on for react depending (received and 2019 objects, 16, interact October approved molecules and CA, Chiral Berkeley, California, of University Bell, T. Alexis by Edited aoaoyo hsclCeity T Z ETH Chemistry, Physical of Laboratory h eeomn fmr estv ehd,apial oiso- to applicable methods, sensitive more of development The ihcia eetr n ihcia ih.Tefre effect former The light. chiral differently with interact and molecule receptors chiral chiral a with of enantiomers two he | ihhroi generation high-harmonic 10 | −6 femtochirality to orner ¨ 10 a ailZindel Daniel , −3 a,1 eaiesga hne.Nevertheless, changes. signal relative | iclrdichroism circular rc,89 Z 8093 urich, ¨ a V , tSvoboda ´ ıt rc,Switzerland urich, ¨ | a la Bommeli Elias , 1073/pnas.1907189116/-/DCSupplemental. y at online information supporting contains article This 1 BY-NC-ND) (CC 4.0 NoDerivatives License distributed under is article access open This Submission. y Direct PNAS a is article This interest.y competing no declare authors The ...... n ..cnrbtdnwraet/nltctos ..analyzed D.B. tools; reagents/analytic paper. the new wrote contributed H.J.W. and A.T. D.B. and and research; data; performed M.O., A.T. E.B., and V.S., V.S., D.B., D.Z., research; designed H.J.W. contributions: Author detecting chemical to enantio-specific way underlie the that paves interactions development chiral time the This real reac- photochemical in pathway. a follow along tion to chirality molecular We technique of the evolution dynamics. the the of excited-state and ability resolution, the the demonstrate temporal of its detection samples, background-free gas-phase to sitivity unexcited 35). on (27, recently demonstrated very experimentally molecules pre- and theoretically was (32–34) polarized which dicted circularly fields, laser counterrotating sensi- “bicircular”) two-color chiral (so-called to in unique HHG spectroscopy the of HHG with tivity (29–31) of dynamics sensitivity photochemical established method the This reaction. combines photochemical a undergoing molecules chirality of time-dependent the probing for technique experimental currently direction. research facilities active laser an represents of free-electron X-ray from extension derived and radiation The high-harmonic soft-X-ray and reactions. UV extreme excited photochemical to highly TR-PECD than in consequence, dynamics rather a probing As to states (28). restricted domain remained by visible has regime the it in single-photon-ionization pulses only laser the discrim- far using chiral in so 13% has demonstrated to (TR-PECD) up been PECD achieve Time-resolved discrimination, to (27). chiral shown ination been low has very latter yields the still technique former the owo orsodnemyb drse.Eal [email protected] Email: addressed. be may correspondence whom To tt hog h rniinsaergo otefia achiral ground final the electronic to unexcited region products. transition-state the the during from through chirality state reaction molecular we chemical of fields, evolution a laser temporal polarized the circularly follow with counterrotating technique in transient-grating report HHG the near-infrared we Combining intense work, fields. tailored present laser in high- the (HHG) technique: generation In unlikely harmonic seemingly phase. a gas out with breakthrough remained the this has in reaction chemical reach a of during chirality observa- of (femtosecond) this tion of real-time spite In a scents. importance, of as perception fundamental our such or drugs interactions, the of activity biomolecular is the recognition most chiral governing This right). principle on vs. depending (left differently, handedness react their and interact molecules Chiral Significance h e datgso u uppoetcnqeaeissen- its are technique pump–probe our of advantages key The general nearly and ultrafast, all-optical, an introduce we Here, a aulOchsner Manuel , a nrsTehlar Andres , . y raieCmosAttribution-NonCommercial- Commons Creative y www.pnas.org/lookup/suppl/doi:10. 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CHEMISTRY reactions. Building on the self-probing capabilities of high- Fig. S1). As revealed by the data presented in SI Appendix, the harmonic spectroscopy (36, 37), our technique also provides typically achieved diffraction efficiencies reached up to 7 to 8%. access to the attosecond electron dynamics (38) of the underlying The experiment consisted of measuring the intensity of the chiral response (27) and its dependence on the chemical-reaction diffracted and undiffracted high-harmonic emission as a function pathway. With the recent extensions of high-harmonic spec- of the time delay between the excitation and probe pulses. The troscopy to solids (39–41) and liquids (42), our technique will dynamics of the 2-iodobutane photodissociation were investi- rapidly become applicable to all phases of matter. In the liq- gated for pump–probe delays ∆t spanning the range from −0.15 uid phase, it will give access to the interactions underlying chiral to 5 ps. Fig. 2, Lower Right shows the short-time evolution of recognition. In the solid state, it might open approaches to elu- signal in harmonic order 23 ([H23] of 1,800 nm, ∼ 15.8 eV) cidate dynamics in chiral crystals, such as chiral magnetic or recorded in racemic 2-iodobutane. The orange curve represents magnetoelectric effects. Its all-optical nature paired with its high the undiffracted intensity (Im=0), while the averaged diffracted degree of chiral discrimination will facilitate its application to (m = ±1) signals are shown in dark green. Temporal overlap of dense or highly charged forms of matter. the pump and probe pulses led to high-order wave mixing (45), which appeared spatially separated from the other signals on the Results detector (SI Appendix, Fig. S1). This wave-mixing signal, aver- The light-induced dissociation of 2-iodobutane (2 − C4H9I), aged over its two components (wm = ±1), is shown as black line. depicted in Fig. 1, was selected as an illustrative chemical reac- It accurately determines the characteristic cross-correlation time tion. Photoexcitation of this molecule at 266 nm accesses the A˜ of the experiment (≈ 45 fs). 3 + band and mainly populates the Q0 state in a parallel transition, The temporal evolution of the undiffracted intensities is qual- as revealed by magnetic CD measurements (43). The repulsive itatively similar for all harmonic orders, as is the time evolution 3 + potential-energy curves of the Q0 and the two close-lying elec- of all observed diffracted intensities. We characterized the pho- 3 1 tronic states ( Q1 and Q1) are given in SI Appendix, Figs. S3 and todissociation dynamics observed in each harmonic order by 3 + S4. Following excitation to the Q0 state, the molecule dissoci- quantifying the exponential time scale of intensity buildup in ates into a 2-butyl radical and a spin-orbit–excited iodine atom the diffracted signals τrise, defined by the phenomenological ∗ 2 (I , P1/2) on an ultrafast time scale. kinetic expressions given in SI Appendix, Eqs. S1 and S2. The The breakage of the C–I bond also induces a major modifi- extracted values of τrise, averaged over multiple measurements, cation of the chiral structure of the molecule. The main idea of are listed in SI Appendix, Table I. Notably, the observed (aver- our work is to map out the temporal evolution of the molecular aged) dissociation time scale (τrise ≈ 340 fs) is longer than the chirality as the laser-induced photodissociation takes its course. estimations from wave-packet calculations (SI Appendix, section We thereby answer the following questions. Is the 2-butyl radical IV) or extrapolations from previous studies (see discussion in ref. produced in a chiral or achiral state? How fast do the signatures 46). This observation is in line with the conclusions from previ- of the changing chirality evolve from the reactant to the prod- ous TG-HHG studies on the photodissociation dynamics of Br2 uct state? Which properties of molecular chirality is our method (29) and other alkyl halides employing linearly polarized driving sensitive to? fields (47). The experimental setup is illustrated in Fig. 2. A transient grat- We now turn to the characterization of the time-dependent ing [TG (29, 30, 44)] was produced by crossing two linearly polar- chirality during the photodissociation. Enantiomerically en- ized, vertically offset 266-nm pulses in a supersonic expansion riched samples (ee ∼ 60 − 65%) of (R)- and (S)-2-iodobutane of gaseous 2-iodobutane. A periodic intensity-variation pattern were synthesized in-house as described in SI Appendix, section II. was produced in the focal plane, and, as efficient photoexcita- The chirality sensitive measurements were performed by mon- tion was restricted to the high-intensity regions, this modulation itoring the signal of the undiffracted emission (Im=0) as the translated into alternating planes of excited and ground-state ellipticity of the ω and 2ω laser fields constituting the bicircu- molecules. The TG was probed by a bicircular field consist- lar field is varied by rotating the main axis of the achromatic ing of the superposition of 2 circularly polarized ∼40-fs pulses quarter waveplate (QWP) from α = 30◦ to α = 150◦. In this man- centered at 1,800 and 900 nm, respectively, with opposite helici- ner, the polarization of the ω and 2ω laser fields is changed ties. The corresponding electric field describes a Lissajous figure from circular via elliptical to linear and then back to circular resembling a clover leaf, as illustrated in Fig. 2, Left. As the again (with opposite helicity). At both α = 45◦ and α = 135◦, HHG radiation emitted from the individual layers of the grat- the two pulses combined into a bicircular field, but with oppo- ing in the near field is characterized by different amplitudes and site helicities. These two helicities interact differently with the phases, a diffraction pattern is formed in the far field, leading chiral molecules, resulting in a CD effect in the intensity of to a background-free detection of the excitation (SI Appendix, the emitted high-harmonic radiation. SI Appendix, section IC

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

dissociaon 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 chiral structure of the molecule. The leftmost image displays the equilibrium geometry of (R)-2-iodobutane (see SI Appendix for details). The structures in the other images 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 SI Appendix, Fig. S12.

2 of 7 | www.pnas.org/cgi/doi/10.1073/pnas.1907189116 Baykusheva et al. Downloaded by guest on September 30, 2021 Downloaded by guest on September 30, 2021 akseae al. et Baykusheva hs fteeatouesmlsb prxmtl hsamount. this than approximately lower by are samples CDs enantiopure reported the curves the of 65%, those to red 60 of and excesses tiomeric blue as in S)] ( and individual in the [(R) from samples emitted enantiomeric intensities undiffracted-signal the only. the energy expresses photon the and of misalignments function a path as optical CD the com- optical and the ponents of imperfections from resulting asymmetries the the of binations superscript the whereby the averaging by CD observed the ellipticity-resolved for measure quantitative and frequency mental frequency- the n extracting for intensities procedure CD ellipticity-dependent the outlines from separated averaged spatially and is axis) (∼ grating vertical UV. nm optical left-hand extreme 1,800 the curve, XUV, of by (orange 23 normalized; diffracted harmonic orders norm., radiation for undiffracted the axis) the field, (left-hand in far orders observed green) the field In 900-nm nm. + 900 1,800 consisting at field bicircular centered bicircular delayed harmonic light. temporally second a undiffracted its by the generated and is pulse radiation 1,800-nm High-harmonic excitation. a molecular of the modulates spatially which grating intensity 2. Fig. poiebcrua ofiuain (α α configurations bicircular opposite ω ∈ i.3sostehg-amncsga nH9i em of terms in H19 in signal high-harmonic the shows 3 Fig. ic h w mlydsmlshv iia enan- similar have samples employed two the Since Lower. h ifrnilelpiiyrsle D r shown are CDs ellipticity-resolved differential The Upper. [125 eoe h rqec fthe of frequency the denotes rnil fbcrua ihhroi rnin-rtn pcrsoy w oclierpm em r rse ne ml nl,cetn an creating angle, small a under crossed are beams pump noncollinear Two spectroscopy. transient-grating high-harmonic bicircular of Principle ◦ − I 145 R/S CD ◦ (n ω ] ): ± ω and ω CD (n oe Right Lower ) efrhrdfiea ellipticity-averaged an define further We . ω eoddfo aheatoe,where enantiomer, each from recorded 2ω (n = ) ± CD ω ae ed.Ti rcdr minimizes procedure This fields. laser , Z pcfiste2psil eiiycom- helicity possible 2 the specifies α) α (n α min hw h iedpnetsgasosre n2idbtn fe xiaina 6 mfloe yHGdie ya by driven HHG by followed nm 266 at excitation after 2-iodobutane in observed signals time-dependent the shows max ω ntergo ls otetwo the to close region the in , α) CD n th rmtenraie HHG normalized the from ∈ (n amnco h funda- the of harmonic [35 ω , ◦ α)d, − 55 ◦ respectively ], V.Teoii ftetm cl a enstt h aiu ftewv-iigsignal. wave-mixing the of maximum the to set been has scale time the of origin The eV). 15.8 [1] eetbecia epnelf,adtesm a refrthe for true was same the and left, response chiral detectable 2.7% to 0 time averaged after and At detected 4B). all (T Fig. across (H10–H31; 3) orders (Fig. high-harmonic magnitude in increased of significantly property a be state. must ground CD electronic the its of in enantiomeric smallness 2-iodobutane the the with that such linearly the excess, dimin- approximately above), (see scale somewhat sample should our (27) were of CDs methyloxirane CDs enantiopurity limited of the the case by Although ished the (35). in val- limonene than These 4A). and smaller (Fig. notably orders are harmonic of ues 2% range of molecules. whole order unexcited the the across the on is of CD response obtained The chiral the characterize to the to correspond grid. images delay individual pump–probe the the of where points 4, Fig. in sented temporal same The of the contributions. evolution has artifactual of fields elim- sample, possibility driving molecular the the the inating of handedness of the direction changing as rever- rotation effect a that the shows 3 of Fig. in sal curves green the of antisymmetry The ntepeec ftepm uss h Dcagdsg and sign changed CD the pulses, pump the of presence the In pulses pump the of absence the in measured first was CD The 0 ∼ ,temxmlC ausi 1 mutdt o7.The 7%. to 6 to amounted H19 in values CD maximal the ), 2.5% t20f.Atr50f lpe,teewsesnilyno essentially was there elapsed, fs 500 After fs. 250 at | CD fe 0 s n vnulyrahdamxmmof maximum a reached eventually and fs, 100 after CD ± (19 ± (n ω ω )| ) au mutdto amounted value o l amncodr scmatypre- compactly is orders harmonic all for wm = bak and (black) ±1 tH9(i.3, (Fig. H19 at NSLts Articles Latest PNAS ∼ 2% at T 0 m increased , = and Left) (dark ±1 | f7 of 3

CHEMISTRY Fig. 3. (Upper) 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 H19 of 1,800 nm, or ∼ 13.1 eV. (Lower) Ellipticity-dependent CD at H19 for each time step. Deg., degree.

subsequent points on the time grid. Other harmonic orders The results summarized in Fig. 4 lead to the following main exhibited a qualitatively similar behavior, although there were conclusions: 1) A strong chiroptical response appears during differences concerning the time delay maximizing the chiral the excitation by the short 266-nm pulse, which is opposite in response (see, for instance, H10 and H13 in Fig. 4, for which sign to that of the unexcited molecules; 2) the induced chiral |CD| maximized at ∆t = 250 and 100 fs, respectively). response persists up to & 250 fs, after which it decays, signaling

A D

B E

C F

Fig. 4. Ellipticity-averaged CD observed in 2-iodobutane as a function of the photon energy. The data in each image are recorded at a different value of the pump–probe delay ∆t.

4 of 7 | www.pnas.org/cgi/doi/10.1073/pnas.1907189116 Baykusheva et al. Downloaded by guest on September 30, 2021 Downloaded by guest on September 30, 2021 ainvathe via tation 13% to (27). (up result can CD dynamics substantial induced (10 the a small in extremely changes are corresponding the that, shown dynamics, has although analysis laser-induced previous cross- Our the the above. by mentioned conveyed in compo- channels exclusively is pulses magnetic-field sensitivity chiral laser the weak driving whereby the emerges the CD of of is ionization. nent participation that during the state created a through one in the the cation from whereby the different “cross-channels,” with HHG recombines of electron states returning emergence these the between to electron couplings the lead laser-induced of continuum, propagation superposition the During coherent in states. a several electronic in (. If several cation energy the of continuum. leave in the can close ionization in sufficiently field lie electron shells the valence of propagation inter- during occurring the the transitions with magnetic-dipole response and chiral electric- of induced 27, play the (26, linked molecules theo- has chiral previous which from the 48), on HHG of bicircular builds discuss of features model analysis we essential retical Our following, the dynamics. captures the chiral that observed In chi- model progresses. molecular theoretical reaction the a the of evolution as our time-dependent rality of the origin by dynam- the caused these CD as Since observed dynamics ps. the rotational 5 than exclude to observations. 11 longer can of we much rotational the scale ics, are expansion, time supersonic scales a our time in on temper- K rotational decays 30 expected anisotropy to typical 5 for of that These atures show pulses. S14, the in Fig. pump of summarized and the dependence are by which time caused per- calculations, the 2-iodobutane have of on we partial alignment Therefore, calculations (33), decay. detailed rotational field their formed subsequent laser explain the orien- the and could the CDs, to dephasing the on relative enhance depend can molecule strongly alignment the the HHG of of bicircular tation alignment in Since partial effects scale. time a picosecond CD the to on decays leads the that molecules effect transition- of excited direction their This polarization have pulse(s). the that pump along molecules aligned of moments subensemble dipole a of tion chiral the tran- of molecule. the the modifications of of the structure with analysis by associated an induced changes with CD dynamics sient proceed rotational the then of and role photoexcitation the CD. discuss the of we variation First, pump-induced a possible explaining two for basically are mechanisms There interpretation. pro- qualitative and observations a experimental vide the discuss we section, this In Discussion photon chiral emitted the the on 3) dependence strong and energy. 2-iodobutane a state; of displays energy eV) product ionization (9.13 the achiral below an observed response of formation the akseae al. et Baykusheva pump– the quantum-chemistry of the on in function given information is a calculations Detailed us as delay. allows coordinate- moments and probe which curves transition delay, potential-energy relevant dependent pump–probe all the express bijec- to onto is length mapped one- IV). bond the tively section corresponding treatment, Appendix, classical-trajectory the a dis- (SI Within on curve C–I-bond propagation potential-energy the dimensional wave-packet of a value from expectation the [hr tance of evolution the iiigoraayi fthe of analysis our Limiting be to likely most are dynamics CD observed the Therefore, excita- selective the to leads excitation one-photon Resonant CI i(∆t 3 Q safnto ftepm–rb delay pump–probe the of function a as )] 0 + tt sepandaoe efis extracted first we above, explained as state eto III . section Appendix, SI −4 ee nteeeto-oedensity), electron-hole the in level bn yaist photoexci- to dynamics A-band ˜ ntecs fmethyloxirane) of case the in eto VI section Appendix, SI 2 V,strong- eV), ∆ t omn h ifrnilresponse: differential electric- its the instantaneous for forming as the well along as direction aligned field axis C–I-bond its with eobnto tp,aqatttv rdcino h magnitude contain the not of of prediction does quantitative the a model and steps, ionization our recombination the from Since contributions structure-sensitive delay. three the for pump–probe relation the above (H of the with orders obtained harmonic CD selected the shows 5 Fig. magnetic- and electric- sity interval temporal the CD subcycle entirely time-dependent CD The of the recombination. is and within ionization variation between response elements matrix the chiral dipole frame. the in molecular approximations, encoded the the these on in dependence With their directions neglecting to ionization/recombination amounts which [a unity, ionization [a to the is recombination set systems the we many-electron Therefore, and reach. for quantitative of complete process out a HHG still as the response, of chiral description the of profile poral HHG energy frequency-domain photon (26): the delay a pump–probe obtain (at to response used dipole conditions), are experimental channel our each for fs coefficients 1.8 calculated to the 1.4 from ranging ues norwr,telte r acltdwt ihaccuracy high with calculated are latter the probed cation. the work, the of of our dic- structure elements electric In be chiral dipole-transition-matrix geometry-dependent decoupled the mainly magnetic the in as and will the of encoded is response Therefore, variation treated which molecule, chiral the approximation. be by the good can tated of in electron dependence ion response time parent the continuum-propagation chiroptical the the which second, from that the in fact from step, the originates is entirely dynamics chiral ing where duration presented the as over solution, straightforward differen- a ordinary in has coupled that two of equations system tial a to reduces dynamics AX labeled accordingly electron are channels continuum or These the state. same of the the photorecombination with are to and channels four ionization cation Two total the strong-field in process. by to HHG rise formed the gives to this contributing states, channels cationic the in interaction ( (. inpotentials tion the from ionization field ( A X Ω ∆ d(Ω, ˜ ˜ ee eaepiaiyitrse nrtoaiigtetem- the rationalizing in interested primarily are we Here, oee,aseilfaueo u H ceeo prob- of scheme HHG our of feature special a However, experiment the in employed intensities pulse the Considering fe integrating After V. section Appendix, SI CD + + 5 nadto,teeaeto“rs-hnes (XA “cross-channels” two are there addition, In AA. Ω ∆ (Ω, .Udrteepeie,teteteto h laser-induced the of treatment the premises, these Under ). , S pi notosi-ri opnnswt etclioniza- vertical with components spin-orbit two into split , × ˜ I Ω ∆ (Ω; ± CD S p 10 t (Ω) (Ω, ≈ = ) 13 t Ω ∆ (Ω, ) 11.08 W t τ setmtdb acltn h pcrlHGinten- HHG spectral the calculating by estimated is sntexpected. not is X × ) IJ Ω IJ /cm Ω ∆ |d(Ω, ∝ a I ) t rec J p c orsod otesmcasclaction. semiclassical the to corresponds 2 = ) V tts(9 0.Ngetn h spin-orbit the Neglecting 50). (49, states eV) IJ of (∆t 2 τ (∆t IJ Ω n aeegh f18090n) strong- nm), 1,800/900 of wavelengths and ≈ ), max fagvneeto rjcoy(yia val- (typical trajectory electron given a of 9.13 )a t 3 )| ion S I Q ˜ rec J {c 2 ( 0 Ω ∆ (Ω, and + R S Ω ∆ (Ω, ˜ IJ o a for ) 16, ( tt ouae anyteground the mainly populates state Ω ∆ (Ω, (S R (∆t ) ≈ Ω ∆ (Ω, eatoe n subsequently and )-enantiomer H t t 9.68 ) )} arxeeet nEq. in elements matrix )] and 20, (R t ) (with i − 2idbtn molecule )-2-iodobutane τ t safnto fthe of function a as Ω) V n h rtexcited first the and eV) + ) IJ Ω NSLts Articles Latest PNAS S 2π ˜ (∆t ( S X {I S ˜ ˜ Eq. Appendix, SI H ) ( Ω ∆ (Ω, + S , ) safunction a as 31) J ) Ω ∆ (Ω, or {X ∈ } (3/2) t A ˜ ) + ion I t e ) iS , Ω ∆ (Ω, tt of state for A}) ( . | Ω, f7 of 5 τ XX and IJ Ω [3] [2] t S5 )] ) 2

CHEMISTRY separating the two enantiomers and therefore corresponds to an achiral equilibrium geometry. Turning to the remaining discrepancies, we note that the measured CDs appeared to decay more slowly than the calculated ones. Similarly, we noted above that the (nonchiral) signals suggest a longer dissociation time (340 fs) than predicted by our one-dimensional wave-packet calculations. The consis- tent deviation of these two classes of observables from their calculated counterparts most likely originates from neglecting the structure-dependent ionization and recombination matrix elements, because all other quantities have been accurately incorporated into our theoretical model. Conclusion In this article, we have introduced a technique for detecting time-dependent chirality during a chemical reaction. We have applied this technique to study the chirality changes occurring in the course of the photodissociation of 2-iodobutane. With the aid of a conceptually simple theoretical treatment based on high-level ab initio quantum-chemical calculations, we have Fig. 5. Time-dependent CD signal, evaluated according to Eq. 3 at photon energies corresponding to H16, H20, and H31 of 1,800 nm. The instanta- been able to correlate the time evolution of the CD signal with neous direction of the ionizing bicircular field is set parallel to the C–I-bond the coordinate dependence of the electric- and magnetic-dipole axis. The signal is averaged over the azimuthal angle associated with matrix elements that encode the chiral response in the HHG this axis. process. This technique is sufficiently sensitive to be applicable to the by using modern quantum-chemistry methods (SI Appendix, gas phase, but is equally applicable to liquids (42) and solids section III). (39) in future experiments. Its relatively large CD effects, com- Our results predict a rapid increase of the CD signal at early parable in magnitude to PECD, combined with its all-optical time delays, followed by one relatively sharp local maximum nature make it a powerful chiral-sensitive method for detect- around 30–40 fs, a broad shoulder feature around 80–90 fs, ing ultrafast changes in molecular chirality. The ability to probe followed by a monotonous decay by two to three orders of chiral photochemical processes on such time scales opens up a magnitude within ∼250 to 300 fs. The overall dynamics of the variety of possibilities for investigating chiral-recognition phe- calculated CDs therefore capture the main features of the exper- nomena, such as the processes that determine the outcome of imental results, which show local maxima around 100 fs and enantioselective chemical reactions. Paired with recent devel- a subsequent decay. Moreover, the results in Fig. 5 predict a opments in condensed-phase high-harmonic spectroscopy, our pronounced spectral dependence of the time-dependent chiral technique will rapidly be applied to all phases of matter, where response, which is also present in the experimental results shown it will unlock the study of a range of chiral phenomena on in Fig. 4. This comparison shows that our simple model captures ultrashort time scales. the salient features of the measured chiral dynamics. Our calculations further allow us to conclude that the decay of the chiral Methods response and its vanishing for long delays reflect the progressive Details on the experimental setup and data evaluation are given in loss of chirality during the C–I-bond-breaking process. We have SI Appendix, section I. The synthesis of enantiomerically enriched 2- carried out a detailed comparison of the predictions of our the- iodobutane is described in SI Appendix, section II. The theoretical work, oretical model, including or neglecting the planarization of the including the quantum-chemical ab initio calculations, the quantum- 2-butyl radical (SI Appendix, section III B). This comparison has dynamical calculations, and the CD calculations, is given in SI Appendix, shown that the geometric relaxation of the 2-butyl radical does sections III–VIII. not qualitatively change the predicted CD dynamics, which are therefore dominated by the detachment of the iodine atom from Data Availability. The data presented in this article are available from the the molecular backbone. The observed disappearance of the CD corresponding author upon request. therefore reflects the loss of chirality of the dissociating system as ACKNOWLEDGMENTS. D.B. thanks Prof. Frank Neese for helpful discus- a whole during its transformation into fragments that are achiral sions regarding the calculation of the distance-dependent magnetic dipole on their own. This conclusion is further supported by our analy- moments. We thank ETH Zurich for the allocation of computational sis of the potential-energy surface of the 2-butyl radical along the resources on the EULER cluster. We thank Prof. Ivan Powis (Nottingham) for suggesting to study 2-iodobutane in this work. This work was sup- internal coordinate that interconverts its two enantiomers. The ported by Swiss National Science Foundation Project 200021 172946 and calculations presented in SI Appendix, section VIII corroborate the National Center of Competence in Research–Molecular Ultrafast Science the fact that the vibrational zero-point level lies above the barrier and Technology.

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