Quaternary Charge-Transfer Complex Enables Photoenzymatic Intermolecular Hydroalkylation of Olefins.

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, α-chloroamide, 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.

Surface Perturbation Training to Prevent Falls in Older Adults: A Highly Pragmatic, Randomized Controlled Trial.

BACKGROUND: Falls are the leading cause of injuries among older adults, and trips and slips are major contributors to falls. OBJECTIVE: The authors sought to compare the effectiveness of adding a component of surface perturbation training to usual gait/balance training for reducing falls and fall-related injury in high-risk older adults referred to physical therapy. DESIGN: This was a multi-center, pragmatic, randomized, comparative effectiveness trial. SETTING: Treatment took place within 8 outpatient physical therapy clinics. PATIENTS: This study included 506 patients 65+ years of age at high fall risk referred for gait/balance training. INTERVENTION: This trial evaluated surface perturbation treadmill training integrated into usual multimodal exercise-based balance training at the therapist's discretion versus usual multimodal exercise-based balance training alone. MEASUREMENTS: Falls and injurious falls were assessed with a prospective daily fall diary, which was reviewed via telephone interview every 3 months for 1 year.A total of 211/253 (83%) patients randomized to perturbation training and 210/253 (83%) randomized to usual treatment provided data at 3-month follow-up. At 3 months, the perturbation training group had a significantly reduced chance of fall-related injury (5.7% versus 13.3%; relative risk 0.43) but no significant reduction in the risk of any fall (28% versus 37%, relative risk 0.78) compared with usual treatment. Time to first injurious fall showed reduced hazard in the first 3 months but no significant reduction when viewed over the entire first year. LIMITATIONS: The limitations of this trial included lack of blinding and variable application of interventions across patients based on pragmatic study design. CONCLUSION: The addition of some surface perturbation training to usual physical therapy significantly reduced injurious falls up to 3 months posttreatment. Further study is warranted to determine the optimal frequency, dose, progression, and duration of surface perturbation aimed at training postural responses for this population.

Rhodium-catalyzed endo-selective epoxide-opening cascades: formal synthesis of (-)-brevisin.

[Rh(CO)2Cl]2 is as an effective catalyst for endo-selective cyclizations and cascades of epoxy-(E)-enoate alcohols, thus enabling the synthesis of oxepanes and oxepane-containing polyethers from di- and trisubstituted epoxides. Syntheses of the ABC and EF ring systems of (-)-brevisin via all endo-diepoxide-opening cascades using this method constitute a formal total synthesis and demonstrate the utility of this methodology in the context of the synthesis of marine ladder polyether natural products.

Dipolar side chain control of monolayer morphology: symmetrically substituted 1,5-(mono- and diether) anthracenes at the solution-HOPG interface.

Scanning tunneling microscopy (STM) is used to determine the 2-D unit cell parameters of monolayers self-assembled by twelve symmetrical, 1,5-bis(linear aliphatic ether side chain) anthracenes at the solution-graphite interface. The standard morphology assembled by 1,5-bis(alkyloxymethyl) anthracenes consists of single-lamella domains containing columns of anthracene cores alternating with columns of interdigitated, aliphatic side chains. Adjacent side chains within the aliphatic columns adsorb in antiparallel orientations. The terminal methyl (omega-position) of each side chain lies in registration with the 2-positions of its two neighboring chains ((omega <--> 2)-packing). Anthracenes with diether side chains can generate repulsive or attractive dipole-dipole interactions between proximate ethers of adjacent aliphatic chains. Anthracenes bearing even length side chains with oxygens at the 2- and omega-1 positions or at the 3- and omega-2 positions do not assemble (omega <--> 2)-packed monolayers. Repulsive dipolar interactions between ethers in adjacent side chains raise the energy of (omega <--> 2) morphologies. These "self-repulsive" side chains drive assembly of (omega <--> l)- or (omega <--> 3)-packed morphologies, which enjoy stabilizing dipolar interactions between ethers in adjacent side chains. In stark contrast, anthracenes bearing odd length diether side chains assemble (omega <--> 2)-packed morphologies, regardless of whether adjacent chains suffer zero, one, or two sets of proximate dipole-dipole repulsions. The intrinsic energy gap from (omega <--> 2)- to non-(omega <--> 2)-packed morphologies of odd length side chain anthracenes is, apparently, larger than for even length side chain anthracenes. Overall, the twelve compounds self-assemble seven different morphologies. Distinguishing morphologies, understanding polymorphism within the monolayers, and evaluating the morphological consequences of side chain dipolar interactions is facilitated by viewing the monolayers as assemblies of 1-D, molecular tapes.

Dipolar control of monolayer morphology: spontaneous SAM patterning.

A strategy for controlling relative placements of molecules within multicomponent monolayers at the solution-HOPG interface is demonstrated. The monolayers assemble from complementary pairs of 1,5-bis-alkyldiether-anthracenes bearing self-repelling side chains. Each diether side chain suffers repulsive dipolar interactions if it adsorbs next to an identical side chain in the morphology normally assumed by 1,5-bis-substituted-anthracene monolayers. Complementary side-chain pairs experience attractive dipolar interactions when adsorbed as neighbors in the normal morphology monolayer. The repulsive and attractive forces spontaneously drive formation of a patterned monolayer at the solution-HOPG interface. Each molecule adsorbs in its own row, sandwiched between two rows of the complementary anthracene. These studies demonstrate the viability of using weak dipolar interactions to control molecular placement and monolayer morphology and to pattern multicomponent monolayers.