Polarized XANES Monitors Femtosecond Structural Evolution of Photoexcited Vitamin B12.

Ultrafast, polarization-selective time-resolved X-ray absorption near-edge structure (XANES) was used to characterize the photochemistry of vitamin B12, cyanocobalamin (CNCbl), in solution. Cobalamins are important biological cofactors involved in methyl transfer, radical rearrangement, and light-activated gene regulation, while also holding promise as light-activated agents for spatiotemporal controlled delivery of therapeutics. We introduce polarized femtosecond XANES, combined with UV-visible spectroscopy, to reveal sequential structural evolution of CNCbl in the excited electronic state. Femtosecond polarized XANES provides the crucial structural dynamics link between computed potential energy surfaces and optical transient absorption spectroscopy. Polarization selectivity can be used to uniquely identify electronic contributions and structural changes, even in isotropic samples when well-defined electronic transitions are excited. Our XANES measurements reveal that the structural changes upon photoexcitation occur mainly in the axial direction, where elongation of the axial Co-CN bond and Co-NIm bond on a 110 fs time scale is followed by corrin ring relaxation on a 260 fs time scale. These observations expose features of the potential energy surfaces controlling cobalamin reactivity and deactivation.

Translation of Ligand-Centered Hydrogen Evolution Reaction Activity and Mechanism of a Rhenium-Thiolate from Solution to Modified Electrodes: A Combined Experimental and Density Functional Theory Study.

The homogeneous, nonaqueous catalytic activity of the rhenium-thiolate complex ReL3 (L = diphenylphosphinobenzenethiolate) for the hydrogen evolution reaction (HER) has been transferred from nonaqueous homogeneous to aqueous heterogeneous conditions by immobilization on a glassy carbon electrode surface. A series of modified electrodes based on ReL3 and its oxidized precursor [ReL3][PF6] were fabricated by drop-cast methods, yielding catalytically active species with HER overpotentials for a current density of 10 mA/cm2, ranging from 357 to 919 mV. The overpotential correlates with film resistance as measured by electrochemical impedance spectroscopy and film morphology as determined by scanning and transmission electron microscopy. The lowest overpotential was for films based on the ionic [ReL3][PF6] precursor with the inclusion of carbon black. Stability measurements indicate a 2 to 3 h conditioning period in which the overpotential increases, after which no change in activity is observed within 24 h or upon reimmersion in fresh aqueous, acidic solution. Electronic spectroscopy results are consistent with ReL3 as the active species on the electrode surface; however, the presence of an undetected quantity of catalytically active degradation species cannot be excluded. The HER mechanism was evaluated by Tafel slope analysis, which is consistent with a novel Volmer-Heyrovsky-Tafel-like mechanism that parallels the proposed homogeneous HER pathway. Proposed mechanisms involving traditional metal-hydride processes vs ligand-centered reactivity were examined by density functional theory, including identification and characterization of relevant transition states. The ligand-centered path is energetically favored with protonation of cis-sulfur sites culminating in homolytic S-H bond cleavage with H2 evolution via H atom coupling.

Beyond Metal-Hydrides: Non-Transition-Metal and Metal-Free Ligand-Centered Electrocatalytic Hydrogen Evolution and Hydrogen Oxidation.

A new pathway for homogeneous electrocatalytic H2 evolution and H2 oxidation has been developed using a redox active thiosemicarbazone and its zinc complex as seminal metal-free and transition-metal-free examples. Diacetyl-bis(N-4-methyl-3-thiosemicarbazone) and zinc diacetyl-bis(N-4-methyl-3-thiosemicarbazide) display the highest reported TOFs of any homogeneous ligand-centered H2 evolution catalyst, 1320 and 1170 s(-1), respectively, while the zinc complex also displays one of the highest reported TOF values for H2 oxidation, 72 s(-1), of any homogeneous catalyst. Catalysis proceeds via ligand-centered proton-transfer and electron-transfer events while avoiding traditional metal-hydride intermediates. The unique mechanism is consistent with electrochemical results and is further supported by density functional theory. The results identify a new direction for the design of electrocatalysts for H2 evolution and H2 oxidation that are not reliant on metal-hydride intermediates.

Mechanism of Co-C photodissociation in adenosylcobalamin.

A mechanism of Co-C bond photodissociation in the base-on form of adenosylcobalamin (AdoCbl) was investigated by time-dependent density functional theory (TD-DFT). The key mechanistic step involves singlet radical pair (RP) generation from the first electronically excited state (S1). To connect TD-DFT calculations with ultra-fast excited state dynamics, the potential energy surface (PES) of the S1 state was constructed using Co-C and Co-NIm axial coordinates. The S1 PES can be characterized by two minima separated by a seam resulting from the crossing of two surfaces, of metal-to-ligand charge transfer (MLCT) character near the minimum, and a shallow ligand field (LF) surface at elongated axial bond distances. Only one possible pathway for photolysis (path A) was identified based on energetic grounds. This pathway is characterized by the first elongation of the Co-C bond, followed by photolysis from an LF state where the axial base is partially detached. A new perspective on the photolysis of AdoCbl is then gained by connecting TD-DFT results with available experimental observations.

Electronically excited states of cob(ii)alamin: insights from CASSCF/XMCQDPT2 and TD-DFT calculations.

The low-lying excited states of cob(ii)alamin were investigated using time-dependent density functional theory (TD-DFT). The performance of TD-DFT calculations was further evaluated using CASSCF/XMCQDPT2, where both four-coordinate and five-coordinate models of cob(ii)alamin were considered. Dependence of electronic structure on the axial base was then investigated using TD-DFT. Consistent with previous benchmarks, the BP86 functional provides a reliable description of the electronically excited states. It was found that the dyz + π → dz(2) character of the D1 state increases with respect to the axial base distance, corresponding to a lowering in energy of anti-bonding dz(2) orbitals, leading to near a degeneracy between the ground, and D1 states in the base-off form.

The role of spin-orbit coupling in the photolysis of methylcobalamin.

The photolysis of the methylcobalamin cofactor (MeCbl) in its base-off form was investigated by considering the extent of spin-orbit coupling (SOC). Triplet Co-C photodissociation pathways previously invoked at the density functional theory level using Landau-Zener theory were further validated with ab initio calculations that combine SOC based on multi-state second order perturbation theory. It was determined that SOC is feasible between singlet and triplet states at elongated Co-C distances, leading to photodissociation from the state having dominant σ(dz(2)) character, by either direct coupling with the lowest singlet states or by crossing with SOC mixed triplets.

Mercury Methylation by Cobalt Corrinoids: Relativistic Effects Dictate the Reaction Mechanism.

The methylation of Hg(II) (SCH3 )2 by corrinoid-based methyl donors proceeds in a concerted manner through a single transition state by transfer of a methyl radical, in contrast to previously proposed reaction mechanisms. This reaction mechanism is a consequence of relativistic effects that lower the energies of the mercury 6p1/2 and 6p3/2 orbitals, making them energetically accessible for chemical bonding. In the absence of spin-orbit coupling, the predicted reaction mechanism is qualitatively different. This is the first example of relativity being decisive for the nature of an observed enzymatic reaction mechanism.

Mechanism of Co-C bond photolysis in methylcobalamin: influence of axial base.

A mechanism of Co-C bond photolysis in the base-off form of the methylcobalamin cofactor (MeCbl) and the influence of its axial base on Co-C bond photodissociation has been investigated by time-dependent density functional theory (TD-DFT). At low pH, the MeCbl cofactor adopts the base-off form in which the axial nitrogenous ligand is replaced by a water molecule. Ultrafast excited-state dynamics and photolysis studies have revealed that a new channel for rapid nonradiative decay in base-off MeCbl is opened, which competes with bond dissociation. To explain these experimental findings, the corresponding potential energy surface of the S1 state was constructed as a function of Co-C and Co-O bond distances, and the manifold of low-lying triplets was plotted as a function of Co-C bond length. In contrast to the base-on form of MeCbl in which two possible photodissociation pathways were identified on the basis of whether the Co-C bond (path A) or axial Co-N bond (path B) elongates first, only path B is active in base-off MeCbl. Specifically, path A is inactive because the energy barrier associated with direct dissociation of the methyl ligand is higher than the barrier of intersection between two different electronic states: a metal-to-ligand charge transfer state (MLCT), and a ligand field state (LF) along the Co-O coordinate of the S1 PES. Path B initially involves displacement of the water molecule, followed by the formation of an LF-type intermediate, which possesses a very shallow energy minimum with respect to the Co-C coordinate. This LF-type intermediate on path B may result in either S1/S0 internal conversion or singlet radical pair generation. In addition, intersystem crossing (ISC) resulting in generation of a triplet radical pair is also feasible.

Mechanism of the S1 excited state internal conversion in vitamin B12.

To explain the photostability of vitamin B12, internal conversion of the S1 state was investigated using TD-DFT. The active coordinates for radiationless deactivation were determined to be elongated axial bonds, overcoming a 5.0 kcal mol(-1) energy barrier between the relaxed ligand-to-metal charge transfer (S1), and the ground (S0) states.

Mechanism of Co-C bond photolysis in the base-on form of methylcobalamin.

A mechanism of Co-C bond photodissociation in the base-on form of the methylcobalamin cofactor (MeCbl) has been investigated employing time-dependent density functional theory (TD-DFT), in which the key step involves singlet radical pair generation from the first electronically excited state (S1). The corresponding potential energy surface of the S1 state was constructed as a function of Co-C and Co-Naxial bond distances, and two possible photodissociation pathways were identified on the basis of energetic grounds. These pathways are distinguished by whether the Co-C bond (path A) or Co-Naxial bond (path B) elongates first. Although the final intermediate of both pathways is the same (namely a ligand field (LF) state responsible for Co-C dissociation), the reaction coordinates associated with paths A and B are different. The photolysis of MeCbl is wavelength-dependent, and present TD-DFT analysis indicates that excitation in the visible α/ß band (520 nm) can be associated with path A, whereas excitation in the near-UV region (400 nm) is associated with path B. The possibility of intersystem crossing, and internal conversion to the ground state along path B are also discussed. The mechanism proposed in this study reconciles existing experimental data with previous theoretical calculations addressing the possible involvement of a repulsive triplet state.

Photolytic properties of cobalamins: a theoretical perspective.

This Perspective Article highlights recent theoretical developments, and summarizes the current understanding of the photolytic properties of cobalamins from a computational point of view. The primary focus is on two alkyl cobalamins, methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), as well as two non-alkyl cobalamins, cyanocobalamin (CNCbl) and hydroxocobalamin (HOCbl). Photolysis of alkyl cobalamins involves low-lying singlet excited states where photodissociation of the Co-C bond leads to formation of singlet-born alkyl/cob(ii)alamin radical pairs (RPs). Potential energy surfaces (PESs) associated with cobalamin low-lying excited states as functions of both axial bonds, provide the most reliable tool for initial analysis of their photochemical and photophysical properties. Due to the complexity, and size limitations associated with the cobalamins, the primary method for calculating ground state properties is density functional theory (DFT), while time-dependent DFT (TD-DFT) is used for electronically excited states. For alkyl cobalamins, energy pathways on the lowest singlet surface, connecting metal-to-ligand charge transfer (MLCT) and ligand field (LF) minima, can be associated with photo-homolysis of the Co-C bond observed experimentally. Additionally, energy pathways between minima and seams associated with crossing of S1/S0 surfaces, are the most efficient for internal conversion (IC) to the ground state. Depending on the specific cobalamin, such IC may involve simultaneous elongation of both axial bonds (CNCbl), or detachment of axial base followed by corrin ring distortion (MeCbl). The possibility of intersystem crossing, and the formation of triplet RPs is also discussed based on Landau-Zener theory.

Structural and electronic properties of an [(Al2O3)4](+) cluster.

Density functional theory (DFT) has been applied to investigate the structural and electronic properties of an [(Al2O3)4](+) cluster. Since there is no structural data available from experiment, the geometry of the cluster was obtained based on a model which produced the best agreement with vibrational IR-MPD data. A range of different exchange-correlation functionals were tested, and it was concluded that the best spectral agreement was produced using the CAM-B3LYP and B3LYP functionals, respectively. To further characterize the properties of the cluster, natural bond order analysis was performed, and it was concluded that an appropriate description for the system is [Al8O12](+). The frontier orbitals and spin densities of both cation and neutral systems were considered, and it was concluded that the unrestricted singlet and triplet spin densities of the neutral [Al8O12] system were nearly degenerate, representing a di-radical, with the triplet state being lower in energy.