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Using X-ray free-electron lasers for spectroscopy of molecular catalysts and metalloenzymes

Subjects

Abstract

The metal centres in metalloenzymes and molecular catalysts are responsible for the rearrangement of atoms and electrons during complex chemical reactions, and they enable selective pathways of charge and spin transfer, bond breaking/making and the formation of new molecules. Mapping the electronic structural changes at the metal sites during the reactions gives a unique mechanistic insight that has been difficult to obtain to date. The development of X-ray free-electron lasers (XFELs) enables powerful new probes of electronic structure dynamics to advance our understanding of metalloenzymes. The ultrashort, intense and tunable XFEL pulses enable X-ray spectroscopic studies of metalloenzymes, molecular catalysts and chemical reactions, under functional conditions and in real time. In this Technical Review, we describe the current state of the art of X-ray spectroscopy studies at XFELs and highlight some new techniques currently under development. With more XFEL facilities starting operation and more in the planning or construction phase, new capabilities are expected, including high repetition rate, better XFEL pulse control and advanced instrumentation. For the first time, it will be possible to make real-time molecular movies of metalloenzymes and catalysts in solution, while chemical reactions are taking place.

Key points

  • Femtosecond pulses from X-ray free-electron lasers have unique characteristics that enable X-ray spectroscopy to follow catalytic reactions at the metal centres in chemical and biological systems under functional conditions and in real time.

  • Hard X-ray spectroscopy (>5 keV) is used to study transitions from and to the 1s shell (K-edge) and valence electron orbitals of transition metals involved in catalysis to uncover the geometric and electronic structure of the metal centres.

  • Soft X-ray spectroscopy (<1 keV), transitions from and to the 2p shell (L-edge) of transition metals to the valence orbitals, is used to probe the charge and spin distribution and the degree of covalency of bonds, all of which are critical properties for transition-metal-based catalysis.

  • Nonlinear spectroscopic methods, well established in optical and magnetic resonance energy domains, are now being developed in the X-ray domain.

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Fig. 1: XFEL scheme and experimental design for spectroscopy and diffraction and/or scattering experiments of metalloenzymes and molecular catalysts.
Fig. 2: Hard X-ray spectroscopy at X-ray free-electron lasers.
Fig. 3: Multimodal detection methods in X-ray free-electron laser studies using hard X-rays.
Fig. 4: Soft X-ray spectroscopy at transition-metal L-edges with X-ray free-electron lasers.
Fig. 5: Examples of future X-ray free-electron laser-based nonlinear spectroscopy methods.

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Acknowledgements

J.K., V.K.Y. and J.Y. thank the support from the Director, Office of Science, Office of Basic Energy Sciences (OBES), Division of Chemical Sciences, Geosciences, and Biosciences (CSGB) of the Department of Energy (DOE) under contract DE-AC02-05CH11231. The National Institutes of Health (NIH) provides funding through grants GM126289 (J.K.) and GM110501 (J.Y.) for instrumentation development for XFEL experiments and metalloenzyme studies, and GM055302 (V.K.Y.) for biochemical aspects of PS II research. This work was supported by the US Department of Energy, Office of Science, Basic Energy Sciences under contract no. DEAC02-76SF00515 (U.B., R.W.S.). P.W. is grateful to R. Jay for providing access to some of the data in Fig. 4 and for fruitful discussions.

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Glossary

Diffraction limit

The fundamental relationship between the size of a light source (D), the wavelength of the light (λ) and the divergence of the light beam (Δθ): Δθ~λD.

Emittance

Transverse emittance refers to the relationship between the angular spread (divergence) of an electron beam and the transverse size of the beam.

Bunch compression

Condensing or squeezing the longitudinal (time) distribution of relativistic electrons in order to increase the peak current.

Self-amplified spontaneous emission

(SASE). Electrons propagating through periodic arrays of magnets exhibit transverse undulating motion, leading to X-ray photon emission. Over distances ~100 m, the X-ray field causes longitudinal microbunching of the electrons at the X-ray wavelength, causing positive feedback on the emission process.

Fluorescence yield

The decay of core-excited states by emission of an X-ray fluorescence photon. X-ray fluorescence is a competitive process and its relative yield depends on the atomic number of the core-excited atom. In 3d transition metals, fluorescence decay dominates for K-edge excitation (31% for Mn)68.

Photon-in photon-out spectroscopy

X-ray spectroscopic methods that separately detect photons incident on the sample (photon-in) and photons leaving the sample (photon-out) to measure the spectroscopic observable. Examples include X-ray absorption spectroscopy in transmission and fluorescence yield mode, X-ray emission spectroscopy and resonant inelastic X-ray scattering.

Auger electron yield

The decay of core-excited states by emission of an Auger electron. Auger decay is a competitive process and its relative yield depends on the atomic number of the core-excited atom. In 3d transition metals, Auger decay dominates for L-edge excitation with a minor fluorescence decay channel (0.5% for Mn)68.

Stimulated emission

The process by which an incident photon of a given energy (or wavelength) triggers an electronic transition in an excited atom or molecule to a lower electronic state, resulting in an emitted photon with the same wavevector, energy and phase as the incident photon.

Fourier transform limit

The lower limit of the duration of a time pulse with a given frequency spectrum. This is based on the fundamental Fourier transform relationship between a time-dependent function and its frequency spectrum, and the lower limit implies a frequency-independent spectral phase.

Seeding

In laser physics, a process in which a signal (typically from a weak laser) is injected into a gain medium (typically from a strong laser) to improve the output signal by stabilizing the wavelength and reducing variations in the output pulse energy and timing (jitter).

Oxidation states

The oxidation state of an atom in a compound describes the degree to which the electron number of an atom has changed compared with the uncharged neutral form of the same atom. In case of redox reactions of first-row transition metals, these changes happen in the 3d shell; hence, the oxidation state is directly related to the number of 3d electrons present.

Spin states

In transition-metal complexes, the spin state refers to the distribution of electrons in the valence shell. Often, there are two distributions possible for the same number of electrons: low-spin or high-spin configurations, having a low or a high number of unpaired electrons, respectively.

Metal–ligand charge-transfer (MLCT) state

MLCT excitations are special cases of charge-transfer excitations in metal complexes. MLCT excited states result from one-electron transitions in which an electron is promoted from a metal-centred to a ligand-centred orbital.

Ligand-field (LF) and charge-transfer (CT) transitions

The valence orbitals in metal complexes can often be classified as either being metal-centred (large amplitude on the metal) or ligand centred (large amplitude on one or several ligands). LF and CT transitions are electronic excitations in metal complexes. LF excitations, often also denoted dd excitations, refer to one-electron transitions between metal-centred orbitals. CT excitations correspond to one-electron transitions between metal-centred and ligand-centred orbitals.

Partial fluorescence yield XAS

Measuring fluorescence as a function of incident photon energy is often denoted partial fluorescence yield X-ray absorption spectroscopy (XAS), and it usually applies to soft X-rays.

Charge and spin densities

Each electron as a particle carries one unit of charge and one unit of spin (alpha/spin up or beta/spin down). In the ensemble averages as described by quantum-chemical calculations, however, charge and spin density distributions in a metal complex or in the active centre of a metalloenzyme can differ, in that alpha (spin up) and beta (spin down) electrons are differently distributed in space.

HOMO-LUMO

In molecular-orbital theory, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) are frontier orbitals of molecules.

Ligand–metal charge-transfer (LMCT) excited state

LMCT excitations are special cases of charge-transfer excitations in metal complexes. LMCT excited states result from one-electron transitions in which an electron is promoted from a ligand-centred to a metal-centred orbital.

10Dq

The ligand-field splitting energy separating eg and t2g orbitals in coordination compounds with octahedral (Oh) symmetry.

Amplified spontaneous emission

(ASE). The spontaneous emission in an ensemble of atoms or molecules, the majority of which are in an electronic excited state. In this scenario, initial spontaneous emission events trigger subsequent stimulated emission events along the propagation path, and the resulting ASE signal grows exponentially.

Seeded stimulated emission

A variation of the stimulated emission process, in which the incident photon is provided in the form of a coherent pulse. Photons with a specific wavelength stimulate the emission of photons with that same wavelength.

Spontaneous emission

The process in which an atom or molecule in an electronic excited state relaxes to a lower-energy electronic state through the emission of a photon.

Core-hole lifetime broadening

The (homogeneous) energy broadening of a core transition due to the finite lifetime of the core-hole. For a Lorentzian line shape, this can be expressed as ΔEFWHMΔT1/e = 0.6589 eV fs, where ΔEFWHM is the full width at half maximum of the linewidth and ΔT1/e is the exponential lifetime (also referred to as dephasing time) of the corresponding core-excited state.

Quantum coupling

The coupling of electronic wavefunctions. As used here, this refers to the mixing of molecular orbitals.

Four-wave mixing

A nonlinear optical (X-ray) process involving four electromagnetic fields (for example, three input fields E1, E2 and E3, contribute to the creation of a new polarization, P). Following a description of the susceptibility χnonlinear in terms of a perturbation expansion, four-wave mixing is a third-order process: P(3) = χ(3)E1E2E3.

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Bergmann, U., Kern, J., Schoenlein, R.W. et al. Using X-ray free-electron lasers for spectroscopy of molecular catalysts and metalloenzymes. Nat Rev Phys 3, 264–282 (2021). https://doi.org/10.1038/s42254-021-00289-3

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