Copper(II) coordination to the intrinsically disordered region of SARS-CoV-2 Nsp1.

The intrinsically disordered C-terminal peptide region of severe acute respiratory syndrome coronavirus 2 nonstructural protein-1 (Nsp1-CT) inhibits host protein synthesis by blocking messenger RNA (mRNA) access to the 40S ribosome entrance tunnel. Aqueous copper(II) ions bind to the disordered peptide with micromolar affinity, creating a possible strategy to restore protein synthesis during host infection. Electron paramagnetic resonance (EPR) and tryptophan fluorescence measurements on a 10-residue model of the disordered protein region (Nsp1-CT10), combined with advanced quantum mechanics calculations, suggest that the peptide binds to copper(II) as a multidentate ligand. Two optimized computational models of the copper(II)-peptide complexes were derived: One corresponding to pH 6.5 and the other describing the complex at pH 7.5 to 8.5. Simulated EPR spectra based on the calculated model structures are in good agreement with experimental spectra.

Tryptophan extends the life of cytochrome P450.

Powerfully oxidizing enzymes need protective mechanisms to prevent self-destruction. The flavocytochrome P450 BM3 from Priestia megaterium (P450BM3) is a self-sufficient monooxygenase that hydroxylates fatty acid substrates using O2 and NADPH as co-substrates. Hydroxylation of long-chain fatty acids (≥C14) is well coupled to O2 and NADPH consumption, but shorter chains (≤C12) are more poorly coupled. Hydroxylation of p-nitrophenoxydodecanoic acid by P450BM3 produces a spectrophotometrically detectable product wherein the coupling of NADPH consumption to product formation is just 10%. Moreover, the rate of NADPH consumption is 1.8 times that of O2 consumption, indicating that an oxidase uncoupling pathway is operative. Measurements of the total number of enzyme turnovers before inactivation (TTN) indicate that higher NADPH concentrations increase TTN. At lower NADPH levels, added ascorbate increases TTN, while a W96H mutation leads to a decrease. The W96 residue is about 7 Å from the P450BM3 heme and serves as a gateway residue in a tryptophan/tyrosine (W/Y) hole transport chain from the heme to a surface tyrosine residue. The data indicate that two oxidase pathways protect the enzyme from damage by intercepting the powerfully oxidizing enzyme intermediate (Compound I) and returning it to its resting state. At high NADPH concentrations, reducing equivalents from the flavoprotein are delivered to Compound I by the usual reductase pathway. When NADPH is not abundant, however, oxidizing equivalents from Compound I can traverse a W/Y chain, arriving at the enzyme surface where they are scavenged by reductants. Ubiquitous tryptophan/tyrosine chains in highly oxidizing enzymes likely perform similar protective functions.

Control of protein activity by photoinduced spin polarized charge reorganization.

Considerable electric fields are present within living cells, and the role of bioelectricity has been well established at the organismal level. Yet much remains to be learned about electric-field effects on protein function. Here, we use phototriggered charge injection from a site-specifically attached ruthenium photosensitizer to directly demonstrate the effect of dynamic charge redistribution within a protein. We find that binding of an antibody to phosphoglycerate kinase (PGK) is increased twofold under illumination. Remarkably, illumination is found to suppress the enzymatic activity of PGK by a factor as large as three. These responses are sensitive to the photosensitizer position on the protein. Surprisingly, left (but not right) circularly polarized light elicits these responses, indicating that the electrons involved in the observed dynamics are spin polarized, due to spin filtration by protein chiral structures. Our results directly establish the contribution of electrical polarization as an allosteric signal within proteins. Future experiments with phototriggered charge injection will allow delineation of charge rearrangement pathways within proteins and will further depict their effects on protein function.

Electronic Structures and Photoredox Chemistry of Tungsten(0) Arylisocyanides.

ConspectusThe high energy barriers associated with the reaction chemistry of inert substrates can be overcome by employing redox-active photocatalysts. Research in this area has grown exponentially over the past decade, as transition metal photosensitizers have been shown to mediate challenging organic transformations. Critical for the advancement of photoredox catalysis is the discovery, development, and study of complexes based on earth-abundant metals that can replace and/or complement established noble-metal-based photosensitizers.Recent work has focused on redox-active complexes of 3d metals, as photosensitizers containing these metals most likely would be scalable. Although low lying spin doublet ("spin flip") excited states of chromium(III) and metal-to-ligand charge transfer (MLCT) excited states of copper(I) have relatively long lifetimes, the electronic excited states of many other 3d metal complexes fall on dissociative potential energy surfaces, owing to the population of highly energetic σ-antibonding orbitals. Indeed, we and other investigators have shown that low lying spin singlet and triplet excited states of robust closed-shell metal complexes are too short-lived at room temperature to engage in bimolecular reactions in solutions. In principle, this problem could be overcome by designing and constructing 3d metal complexes containing strong field π-acceptor ligands, where thermally equilibrated MLCT or intraligand charge transfer excited states might fall well below the upper surfaces of dissociative 3d-3d states. Notably, such design elements have been exploited by investigators in very recent work on redox-active iron(II) systems. Another approach, one we have actively pursued, is to design and construct closed-shell complexes of earth-abundant 5d metals containing very strong π-acceptor ligands, where vertical excitation of 5d-5d excited states at the ground state geometry would require energies far above minima in the potential surfaces of MLCT excited states. As this requirement is met by tungsten(0) arylisocyanides, these complexes have been the focus of our work aimed at the development of robust redox-active photosensitizers.In the following Account, we review recent work on homoleptic tungsten(0) arylisocyanides. Originally reported by our group 45 years ago, W(CNAr)6 complexes have exceptionally large one- and two-photon absorption cross-sections. One- or two-photon excitation produces relatively long-lived (hundreds of nanoseconds to microsecond) MLCT excited states in high yields. These MLCT excited states, which are very strong reductants with E°(W+/*W0) = -2.2 to -3.0 V vs Fc[+/0], mediate photocatalysis of organic reactions with both visible and near-infrared (NIR) light. Here, we highlight design principles that led to the development of three generations of W(CNAr)6 photosensitizers; and we discuss likely steps in the mechanism of a prototypal W(CNAr)6-catalyzed base-promoted homolytic aromatic substitution reaction. Among the many potential applications of these very bright luminophores, two-photon imaging and two-photon-initiated polymerization are ones we plan to pursue.

Reversible Reactions of Nitric Oxide with a Binuclear Iron(III) Nitrophorin Mimic.

Construction of functional synthetic systems that can reversibly bind and transport the most biologically important gaseous molecules, oxygen and nitric oxide (NO), remains a contemporary challenge. Myoglobin and nitrophorin perform these respective tasks employing a protein-embedded heme center where one axial iron site is occupied by a histidine residue and the other is available for small molecule ligation, structural features that are extremely difficult to mimic in protein-free environments. Indeed, the hitherto reported designs rely on sophisticated multistep syntheses for limiting access to one of the two axial coordination sites in small molecules. We have shown previously that binuclear Ga(III) and Al(III) corroles have available axial sites, and now report a redox-active binuclear Fe(III) corrole, (1-Fe)2 , in which each (corrolato)Fe(III) center is 5-coordinate, with one axial site occupied by an imidazole from the other corrole. The binuclear structure is further stabilized by attractive forces between the corrole π systems. Reaction of NO with (1-Fe)2 affords mononuclear iron nitrosyls, and of functional relevance, the reaction is reversible: nitric oxide is released upon purging the nitrosyls with inert gases, thereby restoring (1-Fe)2 in solutions or films.

Photoinduced hole hopping through tryptophans in proteins.

Hole hopping through tryptophan/tyrosine chains enables rapid unidirectional charge transport over long distances. We have elucidated structural and dynamical factors controlling hopping speed and efficiency in two modified azurin constructs that include a rhenium(I) sensitizer, Re(His)(CO)3(dmp)+, and one or two tryptophans (W1, W2). Experimental kinetics investigations showed that the two closely spaced (3 to 4 Å) intervening tryptophans dramatically accelerated long-range electron transfer (ET) from CuI to the photoexcited sensitizer. In our theoretical work, we found that time-dependent density-functional theory (TDDFT) quantum mechanics/molecular mechanics/molecular dynamics (QM/MM/MD) trajectories of low-lying triplet excited states of ReI(His)(CO)3(dmp)+-W1(-W2) exhibited crossings between sensitizer-localized (*Re) and charge-separated [ReI(His)(CO)3(dmp•-)/(W1•+ or W2•+)] (CS1 or CS2) states. Our analysis revealed that the distances, angles, and mutual orientations of ET-active cofactors fluctuate in a relatively narrow range in which the cofactors are strongly coupled, enabling adiabatic ET. Water-dominated electrostatic field fluctuations bring *Re and CS1 states to a crossing where *Re(CO)3(dmp)+←W1 ET occurs, and CS1 becomes the lowest triplet state. ET is promoted by solvation dynamics around *Re(CO)3(dmp)+(W1); and CS1 is stabilized by Re(dmp•-)/W1•+ electron/hole interaction and enhanced W1•+ solvation. The second hop, W1•+←W2, is facilitated by water fluctuations near the W1/W2 unit, taking place when the electrostatic potential at W2 drops well below that at W1•+ Insufficient solvation and reorganization around W2 make W1•+←W2 ET endergonic, shifting the equilibrium toward W1•+ and decreasing the charge-separation yield. We suggest that multiscale TDDFT/MM/MD is a suitable technique to model the simultaneous evolution of photogenerated excited-state manifolds.

Role of intramolecular hydrogen bonds in promoting electron flow through amino acid and oligopeptide conjugates.

Elucidating the factors that control charge transfer rates in relatively flexible conjugates is of importance for understanding energy flows in biology as well as assisting the design and construction of electronic devices. Here, we report ultrafast electron transfer (ET) and hole transfer (HT) between a corrole (Cor) donor linked to a perylene-diimide (PDI) acceptor by a tetrameric alanine (Ala)4 Selective photoexcitation of the donor and acceptor triggers subpicosecond and picosecond ET and HT. Replacement of the (Ala)4 linker with either a single alanine or phenylalanine does not substantially affect the ET and HT kinetics. We infer that electronic coupling in these reactions is not mediated by tetrapeptide backbone nor by direct donor-acceptor interactions. Employing a combination of NMR, circular dichroism, and computational studies, we show that intramolecular hydrogen bonding brings the donor and the acceptor into proximity in a "scorpion-shaped" molecular architecture, thereby accounting for the unusually high ET and HT rates. Photoinduced charge transfer relies on a (Cor)NH…O=C-NH…O=C(PDI) electronic-coupling pathway involving two pivotal hydrogen bonds and a central amide group as a mediator. Our work provides guidelines for construction of effective donor-acceptor assemblies linked by long flexible bridges as well as insights into structural motifs for mediating ET and HT in proteins.

Boronated Cyanometallates.

Thirteen boronated cyanometallates [M(CN-BR3)6]3/4/5- [M = Cr, Mn, Fe, Ru, Os; BR3 = BPh3, B(2,4,6,-F3C6H2)3, B(C6F5)3] and one metalloboratonitrile [Cr(NC-BPh3)6]3- have been characterized by X-ray crystallography and spectroscopy [UV-vis-near-IR, NMR, IR, spectroelectrochemistry, and magnetic circular dichroism (MCD)]; CASSCF+NEVPT2 methods were employed in calculations of electronic structures. For (t2g)5 electronic configurations, the lowest-energy ligand-to-metal charge-transfer (LMCT) absorptions and MCD C-terms in the spectra of boronated species have been assigned to transitions from cyanide π + B-C borane σ orbitals. CASSCF+NEVPT2 calculations including t1u and t2u orbitals reproduced t1u/t2u → t2g excitation energies. Many [M(CN-BR3)6]3/4- complexes exhibited highly electrochemically reversible redox couples. Notably, the reduction formal potentials of all five [M(CN-B(C6F5)3)6]3- anions scale with the LMCT energies, and Mn(I) and Cr(II) compounds, [K(18-crown-6)]5[Mn(CN-B(C6F5)3)6] and [K(18-crown-6)]4[Cr(CN-B(C6F5)3)6], are surprisingly stable. Continuous-wave and pulsed electron paramagnetic resonance (EPR; hyperfine sublevel correlation) spectra were collected for all Cr(III) complexes; as expected, 14N hyperfine splittings are greater for (Ph4As)3[Cr(NC-BPh3)6] than for (Ph4As)3[Cr(CN-BPh3)6].

Addressing the challenge of carbon-free energy.

This century will witness a major transformation in how energy is acquired, stored, and utilized globally. The impetus for this change comes from the deep impacts that both developed and developing societies have had on our planet's environment during the past century, and the projections going forward of what will happen if we do not act transformatively within the next 2 decades. This paper describes the basis for a meeting held in October 2018 on the need for decarbonization in our energy landscape, and specifically the status and challenges of the science that provides the foundation for such technology. Within the realm of decarbonization in energy generation lies the science of solar energy conversion using new or improved photovoltaic materials and artificial photosynthesis for water splitting and other energy-storing reactions. The intimately related issue of renewable energy storage is being addressed with new strategies, materials, and approaches under current investigation and development. The need to improve the interactions between scientists working on these connected but separately considered challenges and on the transition of scientific achievement to practical application was also addressed, with specific efforts enumerated.

Frustration Dynamics and Electron-Transfer Reorganization Energies in Wild-Type and Mutant Azurins.

Long-range electron tunneling through metalloproteins is facilitated by evolutionary tuning of donor-acceptor electronic couplings, formal electrochemical potentials, and active-site reorganization energies. Although the minimal frustration of the folding landscape enables this tuning, residual frustration in the vicinity of the metallocofactor can allow conformational fluctuations required for protein function. We show here that the constrained copper site in wild-type azurin is governed by an intricate pattern of minimally frustrated local and distant interactions that together enable rapid electron flow to and from the protein. In contrast, sluggish electron transfer reactions (unfavorable reorganization energies) of active-site azurin variants are attributable to increased frustration near to as well as distant from the copper site, along with an exaggerated oxidation-state dependence of both minimally and highly frustrated interaction patterns.

Longitudinal manganese-enhanced magnetic resonance imaging of neural projections and activity.

Manganese-enhanced magnetic resonance imaging (MEMRI) holds exceptional promise for preclinical studies of brain-wide physiology in awake-behaving animals. The objectives of this review are to update the current information regarding MEMRI and to inform new investigators as to its potential. Mn(II) is a powerful contrast agent for two main reasons: (1) high signal intensity at low doses; and (2) biological interactions, such as projection tracing and neural activity mapping via entry into electrically active neurons in the living brain. High-spin Mn(II) reduces the relaxation time of water protons: at Mn(II) concentrations typically encountered in MEMRI, robust hyperintensity is obtained without adverse effects. By selectively entering neurons through voltage-gated calcium channels, Mn(II) highlights active neurons. Safe doses may be repeated over weeks to allow for longitudinal imaging of brain-wide dynamics in the same individual across time. When delivered by stereotactic intracerebral injection, Mn(II) enters active neurons at the injection site and then travels inside axons for long distances, tracing neuronal projection anatomy. Rates of axonal transport within the brain were measured for the first time in "time-lapse" MEMRI. When delivered systemically, Mn(II) enters active neurons throughout the brain via voltage-sensitive calcium channels and clears slowly. Thus behavior can be monitored during Mn(II) uptake and hyperintense signals due to Mn(II) uptake captured retrospectively, allowing pairing of behavior with neural activity maps for the first time. Here we review critical information gained from MEMRI projection mapping about human neuropsychological disorders. We then discuss results from neural activity mapping from systemic Mn(II) imaged longitudinally that have illuminated development of the tonotopic map in the inferior colliculus as well as brain-wide responses to acute threat and how it evolves over time. MEMRI posed specific challenges for image data analysis that have recently been transcended. We predict a bright future for longitudinal MEMRI in pursuit of solutions to the brain-behavior mystery.

Copper(II) Binding to the Intrinsically Disordered C-Terminal Peptide of SARS-CoV-2 Virulence Factor Nsp1.

The first encoded SARS-CoV-2 protein (Nsp1) binds to the human 40S ribosome and blocks synthesis of host proteins, thereby inhibiting critical elements of the innate immune response. The final 33 residues of the natively unstructured Nsp1 C-terminus adopt a helix-turn-helix geometry upon binding to the ribosome. We have characterized the fluctuating conformations of this peptide using circular dichroism spectroscopy along with measurements of tryptophan fluorescence and energy transfer. Tryptophan fluorescence decay kinetics reveal that copper(II) binds to the peptide at micromolar concentrations, and electron paramagnetic resonance spectroscopy indicates that the metal ion coordinates to the lone histidine residue.

Photoredox Catalysis Mediated by Tungsten(0) Arylisocyanides in 1,2-Difluorobenzene.

We have studied the photochemical cyclization of 1-(2-iodobenzyl)-pyrrole (IBP) and 1-(2-bromobenzyl)-pyrrole (BBP) to 5H-pyrrolo[2,1-a]isoindol catalyzed by W(CNDipp)6 (CNDipp = 2,6-diisopropylphenylisocyanide) in 1,2-difluorobenzene (DFB). Irradiation (445 nm) of W(CNDipp)6 (5 mol %) in DFB solution converted 78% of IBP (50 mM) to product after 1 h (16 turnovers). Addition of tetra-n-butyl ammonium hexafluorophosphate (TBAPF6) (0.2 M) to the DFB solution led to rapid photoinduced disappearance of W(CNDipp)6 but, remarkably, did not inhibit photochemical cyclization of IBP, indicating that IBP cyclization could be driven by a nonluminescent photocatalyst.

Excitation-Wavelength-Dependent Photophysics of d8d8 Di-isocyanide Complexes.

Binuclear Rh(I) and Ir(I) TMB (2,5-dimethyl-2,5-diisocyanohexane) and dimen (1,8-diisocyanomenthane) complexes possess dσ*pσ and dπpσ singlet and triplet excited states that can be selectively excited in the visible and UV spectral regions. Using perturbational spin-orbit TDDFT, we unraveled the detailed character and spin mixing of these electronic transitions and found that delocalization of pσ and dπ orbitals over C≡N- groups makes C≡N stretching vibrations sensitive reporters of electron density and structural changes upon electronic excitation. Picosecond time-resolved infrared spectra measured after visible light, 375 nm, and 316 nm excitation revealed excitation-wavelength-dependent deactivation cascades. Visible light irradiation prepares the 1dσ*pσ state that, after one or two (sub)picosecond relaxation steps, undergoes 70-1300 ps intersystem crossing to 3dσ*pσ, which is faster for the more flexible dimen complexes. UV-excited 1,3dπpσ states decay with (sub)picosecond kinetics through a manifold of high-lying triplet and mixed-spin states to 3dσ*pσ with lifetimes in the range of 6-19 ps (316 nm) and 19-43 ps (375 nm, Ir only), bypassing 1dσ*pσ. Most excited-state conversion and some relaxation steps are accompanied by direct decay to the ground state that is especially pronounced for the most flexible long/eclipsed Rh(dimen) conformer.

Dimeric Corrole Analogs of Chlorophyll Special Pairs.

Chlorophyll special pairs in photosynthetic reaction centers function as both exciton acceptors and primary electron donors. Although the macrocyclic natural pigments contain Mg(II), the central metal in most synthetic analogs is Zn(II). Here we report that insertion of either Al(III) or Ga(III) into an imidazole-substituted corrole affords an exceptionally robust photoactive dimer. Notably, attractive electronic interactions between dimer subunits are relatively strong, as documented by signature changes in NMR and electronic absorption spectra, as well as by cyclic voltammetry, where two well-separated reversible redox couples were observed. EPR spectra of one-electron oxidized dimers closely mimic those of native special pairs, and strong through-space interactions between corrole subunits inferred from spectroscopic and electrochemical data are further supported by crystal structure analyses (3 Å interplanar distances, 5 Å lateral shifts, and 6 Å metal to metal distances).

Photoredox Catalysis Mediated by Tungsten(0) Arylisocyanides.

W(CNAr)6 (CNAr = arylisocyanide) photoreductants catalyze base-promoted homolytic aromatic substitution (BHAS) of 1-(2-iodobenzyl)-pyrrole in deuterated benzene. Moderate to high efficiencies correlate with W(CNAr)6 excited-state reduction potentials upon one-photon 445 nm excitation, with 10 mol % loading of the most powerful photoreductants W(CNDipp)6 (CNDipp = 2,6-diisopropylphenylisocyanide) and W(CNDippPhOMe3)6 (CNDippPhOMe3 = 4-(3,4,5-trimethoxyphenyl)-2,6-diisopropylphenylisocyanide) affording nearly complete conversion. Stern-Volmer quenching experiments indicated that catalysis is triggered by substrate reductive dehalogenation. Taking advantage of the large two-photon absorption (TPA) cross sections of W(CNAr)6 complexes, we found that photocatalysis can be driven with femtosecond-pulsed 810 nm excitation. For both one- and two-photon excitation, photocatalysis was terminated by the formation of seven-coordinate WII-diiodo [WI2(CNAr)5] complexes. Notably, we discovered that W(CNDipp)6 can be regenerated by chemical reduction of WI2(CNDipp)5 with excess ligand present in solution.

Third-Generation W(CNAr)6 Photoreductants (CNAr = Fused-Ring and Alkynyl-Bridged Arylisocyanides).

Homoleptic tungsten(0) arylisocyanides possess photophysical and photochemical properties that rival those of archetypal ruthenium(II) and iridium(III) polypyridine complexes. Previous studies established that extending the π-system of 2,6-diisopropylphenylisocyanide (CNDipp) by coupling aryl substituents para to the isocyanide functionality results in W(CNDippAr)6 oligoarylisocyanide complexes with greatly enhanced metal-to-ligand charge transfer (MLCT) excited-state properties relative to those of W(CNDipp)6. Extending electronic modifications to delineate additional design principles for this class of photosensitizers, herein we report a series of W(CNAr)6 compounds with naphthalene-based fused-ring (CN-1-(2-iPr)-Naph) and CNDipp-based alkynyl-bridged (CNDippCCAr) arylisocyanide ligands. Systematic variation of the secondary aromatic system in the CNDippCCAr platform provides a straightforward method to modulate the photophysical properties of W(CNDippCCAr)6 complexes, allowing access to an extended range of absorption/luminescence profiles and highly reducing excited states, while maintaining the high molar absorptivity MLCT absorption bands, high photoluminescence quantum yields, and long excited-state lifetimes of previous W(CNAr)6 complexes. Notably, W(CN-1-(2-iPr)-Naph)6 exhibits the longest excited-state lifetime of all W(CNAr)6 complexes explored thus far, highlighting the potential benefits of utilizing fused-ring arylisocyanide ligands in the construction of tungsten(0) photoreductants.

Design of robust 2,2'-bipyridine ligand linkers for the stable immobilization of molecular catalysts on silicon(111) surfaces.

The attachment of the 2,2'-bipyridine (bpy) moieties to the surface of planar silicon(111) (photo)electrodes was investigated using ab initio simulations performed on a new cluster model for methyl-terminated silicon. Density functional theory (B3LYP) with implicit solvation techniques indicated that adventitious chlorine atoms, when present in the organic linker backbone, led to instability at very negative potentials of the surface-modified electrode. In prior experimental work, chlorine atoms were present as a trace surface impurity due to required surface processing chemistry, and thus could plausibly result in the observed surface instability of the linker. Free energy calculations for the Cl-atom release process with model silyl-linker constructs revealed a modest barrier (14.9 kcal mol-1) that decreased as the electrode potential became more negative. A small library of new bpy-derived structures has additionally been explored computationally to identify strategies that could minimize chlorine-induced linker instability. Structures with fluorine substituents are predicted to be more stable than their chlorine analogues, whereas fully non-halogenated structures are predicted to exhibit the highest stability. The behavior of a hydrogen-evolving molecular catalyst Cp*Rh(bpy) (Cp* = pentamethylcyclopentadienyl) immobilized on a silicon(111) cluster was explored theoretically to evaluate differences between the homogeneous and surface-attached behavior of this species in a tautomerization reaction observed under reductive conditions for catalytic H2 evolution. The calculated free energy difference between the tautomers is small, hence the results suggest that use of reductively stable linkers can enable robust attachment of catalysts while maintaining chemical behavior on the electrode similar to that exhibited in homogeneous solution.

Vibrational coherence transfer in the ultrafast intersystem crossing of a diplatinum complex in solution.

We investigate the ultrafast transient absorption response of tetrakis(µ-pyrophosphito)diplatinate(II), [Pt2(µ-P2O5H2)4]4- [hereafter abbreviated Pt(pop)], in acetonitrile upon excitation of its lowest singlet 1A2u state. Compared with previously reported solvents [van der Veen RM, Cannizzo A, van Mourik F, Vlcek A, Jr, Chergui M (2011) J Am Chem Soc 133:305-315], a significant shortening of the intersystem crossing (ISC) time (<1 ps) from the lowest singlet to the lowest triplet state is found, allowing for a transfer of vibrational coherence, observed in the course of an ISC in a polyatomic molecule in solution. Density functional theory (DFT) quantum mechanical/molecular mechanical (QM/MM) simulations of Pt(pop) in acetonitrile and ethanol show that high-lying, mostly triplet, states are strongly mixed and shifted to lower energies due to interactions with the solvent, providing an intermediate state (or manifold of states) for the ISC. This suggests that the larger the solvation energies of the intermediate state(s), the shorter the ISC time. Because the latter is smaller than the pure dephasing time of the vibrational wave packet, coherence is conserved during the spin transition. These results underscore the crucial role of the solvent in directing pathways of intramolecular energy flow.

Fluctuating hydrogen-bond networks govern anomalous electron transfer kinetics in a blue copper protein.

We combine experimental and computational methods to address the anomalous kinetics of long-range electron transfer (ET) in mutants of Pseudomonas aeruginosa azurin. ET rates and driving forces for wild type (WT) and three N47X mutants (X = L, S, and D) of Ru(2,2'-bipyridine)2 (imidazole)(His83) azurin are reported. An enhanced ET rate for the N47L mutant suggests either an increase of the donor-acceptor (DA) electronic coupling or a decrease in the reorganization energy for the reaction. The underlying atomistic features are investigated using a recently developed nonadiabatic molecular dynamics method to simulate ET in each of the azurin mutants, revealing unexpected aspects of DA electronic coupling. In particular, WT azurin and all studied mutants exhibit more DA compression during ET (>2 Å) than previously recognized. Moreover, it is found that DA compression involves an extended network of hydrogen bonds, the fluctuations of which gate the ET reaction, such that DA compression is facilitated by transiently rupturing hydrogen bonds. It is found that the N47L mutant intrinsically disrupts this hydrogen-bond network, enabling particularly facile DA compression. This work, which reveals the surprisingly fluctional nature of ET in azurin, suggests that hydrogen-bond networks can modulate the efficiency of long-range biological ET.