We compare the singlet fission dynamics of five pentacene derivatives precipitated to form nanoparticles. Two nanoparticle types were distinguished by differences in their solid-state order and kinetics of triplet formation. Nanoparticles that comprise primarily weakly coupled chromophores lack the bulk structural order of the single crystal and exhibit nonexponential triplet formation kinetics (Type I), while nanoparticles that comprise primarily more strongly coupled chromophores exhibit order resembling that of the bulk crystal and triplet formation kinetics associated with the intrinsic singlet fission rates (Type II). In the highly ordered nanoparticles, singlet fission occurs most rapidly. We relate the molecular packing arrangement derived from the crystal structure of the pentacene derivatives to their singlet fission dynamics and find that slip stacking leads to rapid, subpicosecond singlet fission. We present evidence that exciton delocalization, coincident with an increased relative admixture of charge-transfer configurations in the description of the exciton wave function, facilitates rapid triplet pair formation in the case of single-step singlet fission. We extend the study to include two hexacene derivatives and find that these conclusions are generally applicable. This work highlights acene derivatives as versatile singlet fission chromophores and shows how chemical functionalization affects both solid-state order and exciton interactions and how these attributes in turn affect the rate of singlet fission.

Photoexcitation is a common strategy for initiating radical reactions in chemical synthesis. We found that photoexcitation of flavin-dependent “ene”-reductases changes their catalytic function, enabling these enzymes to promote an asymmetric radical cyclization. This reactivity enables the construction of five-, six-, seven-, and eight-membered lactams with stereochemical preference conferred by the enzyme active site. After formation of a prochiral radical, the enzyme guides the delivery of a hydrogen atom from flavin—a challenging feat for small-molecule chemical reagents. The initial electron transfer occurs through direct excitation of an electron donor-acceptor complex that forms between the substrate and the reduced flavin cofactor within the enzyme active site. Photoexcitation of promiscuous flavoenzymes has thus furnished a previously unknown biocatalytic reaction.

Enzymes are ideal for use in asymmetric catalysis by the chemical industry, because their chemical compositions can be tailored to a specific substrate and selectivity pattern while providing efficiencies and selectivities that surpass those of classical synthetic methods. However, enzymes are limited to reactions that are found in nature and, as such, facilitate fewer types of transformation than do other forms of catalysis. Thus, a longstanding challenge in the field of biologically mediated catalysis has been to develop enzymes with new catalytic functions. Here we describe a method for achieving catalytic promiscuity that uses the photoexcited state of nicotinamide co-factors (molecules that assist enzyme-mediated catalysis). Under irradiation with visible light, the nicotinamide-dependent enzyme known as ketoreductase can be transformed from a carbonyl reductase into an initiator of radical species and a chiral source of hydrogen atoms. We demonstrate this new reactivity through a highly enantioselective radical dehalogenation of lactones-a challenging transformation for small-molecule catalysts. Mechanistic experiments support the theory that a radical species acts as an intermediate in this reaction, with NADH and NADPH (the reduced forms of nicotinamide adenine nucleotide and nicotinamide adenine dinucleotide phosphate, respectively) serving as both a photoreductant and the source of hydrogen atoms. To our knowledge, this method represents the first example of photo-induced enzyme promiscuity, and highlights the potential for accessing new reactivity from existing enzymes simply by using the excited states of common biological co-factors. This represents a departure from existing light-driven biocatalytic techniques, which are typically explored in the context of co-factor regeneration.

Vibronic coherence is observed between two sets of pigments in the cryptophyte light-harvesting protein PC645, whose absorptions are at either end of the spectrum. 2D spectra show specific patterns that are rationalized by the existence of a vibrational resonance linking the pigments and partially delocalizing the excitation. This leads to a modification of the donor-acceptor spectral overlap and a calculable enhancement in the rate of energy transfer. This directed energy transfer between terminal pigments is a design principle likely to be used by cryptophytes.

Bulky side chains promote a molecular packing and intermolecular coupling that effect high-efficiency singlet fission in amorphous solids of pentacene derivatives.

Observation of coherent oscillations in the 2D electronic spectra (2D ES) of photosynthetic proteins has led researchers to ask whether nontrivial quantum phenomena are biologically significant. Coherent oscillations have been reported for the soluble light-harvesting phycobiliprotein (PBP) antenna isolated from cryptophyte algae. To probe the link between spectral properties and protein structure, we determined crystal structures of three PBP light-harvesting complexes isolated from different species. Each PBP is a dimer of αβ subunits in which the structure of the αβ monomer is conserved. However, we discovered two dramatically distinct quaternary conformations, one of which is specific to the genus Hemiselmis. Because of steric effects emerging from the insertion of a single amino acid, the two αβ monomers are rotated by ∼73°to an "open" configuration in contrast to the "closed" configuration of other cryptophyte PBPs. This structural change is significant for the light-harvesting function because it disrupts the strong excitonic coupling between two central chromophores in the closed form. The 2D ES show marked cross-peak oscillations assigned to electronic and vibrational coherences in the closedform PC645. However, such features appear to be reduced, or perhaps absent, in the open structures. Thus cryptophytes have evolved a structural switch controlled by an amino acid insertion to modulate excitonic interactions and therefore the mechanisms used for light harvesting.X-ray crystallography | quantum coherence | protein evolution | excitonic switching L ight-harvesting complexes capture and funnel the energy from light using organic chromophore molecules that are bound to scaffolding proteins. The protein structure thereby sets the relative positions and orientations of the chromophores to control excitation transport. In other words, the protein plays a deciding role in building the "electronic Hamiltonian"-the electronic coupling between chromophores and the chromophoric energy landscape that directs energy flow. This strong connection between structural biology and physics means that ultrafast light-harvesting functions are under genetic and evolutionary control. Cryptophytes, a group of marine and freshwater single-celled algae, are an intriguing example, because one of their light-harvesting antenna complexes was completely reengineered by combining a unique bilin-binding polypeptide with a single subunit from the ancestral red algal phycobilisome (1, 2). Here we report a further example of biological manipulation of this phycobiliprotein (PBP) light-harvesting system. We have discovered an elegant but powerful genetic switch that converts the common form of this PBP into a distinct structural form in which the mechanism underpinning light harvesting is vastly different-in essence because strong excitonic interactions within the PBP are switched from on to off.The crystal structure of the cryptophyte PBP phycoerythrin PE545 from Rhodomonas CS24 showed that the protein is a dimer of two αβ monomers (3, ...

Intermolecular C−C bond-forming reactions are underdeveloped transformations in the field of biocatalysis. Here we report a photoenzymatic intermolecular hydroalkylation of olefins catalyzed by flavin-dependent 'ene'-reductases. Radical initiation occurs via photoexcitation of a rare high-order enzyme-templated charge-transfer complex that forms between an alkene, αchloroamide, and flavin hydroquinone. This unique mechanism ensures that radical formation only occurs when both substrates are present within the protein active site. This active site can control the radical terminating hydrogen atom transfer, enabling the synthesis of enantioenriched γ-stereogenic amides. This work highlights the potential for photoenzymatic catalysis to enable new biocatalytic transformations via previously unknown electron transfer mechanisms.

Flavin-dependent 'ene'-reductases (EREDs) are exquisite catalysts for effecting stereoselective reductions. While these reactions typically proceed through a hydride transfer mechanism, we recently found that EREDs can also catalyze reductive dehalogenations and cyclizations via single electron transfer mechanisms. Here we demonstrate that these enzymes can catalyze redox-neutral radical cyclizations to produce enantioenriched oxindoles from α-haloamides. This transformation is a CC bond forming reaction currently unknown in nature and one for which there are no catalytic asymmetric examples. Mechanistic studies indicate the reaction proceeds via the flavin semiquinone/quinone redox couple, where ground state flavin semiquinone provides the electron for substrate reduction and flavin quinone oxidizes the vinylogous α-amido radical formed after cyclization. This mechanistic manifold was previously unknown for this enzyme family, highlighting the versatility of EREDs in asymmetric synthesis.