Femtosecond to Microsecond Observation of Photochemical Pathways in Nitroaromatic Phototriggers Using Transient Absorption Spectroscopy.

The synthetic accessibility and tolerance to structural modification of phototriggered compounds (PTs) based on the ortho- nitrobenzene (ONB) protecting group have encouraged a myriad of applications including optimization of biological activity, and supramolecular polymerization. Here, a combination of ultrafast transient absorption spectroscopy techniques is used to study the multistep photochemistry of two nitroaromatic phototriggers based on the ONB chromophore, O-(4,5-dimethoxy-2-nitrobenzyl)-l-serine (DMNB-Ser) and O-[(2-nitrophenyl)methyl]-l-tyrosine hydrochloride (NB-Tyr), in DMSO solutions on femtosecond to microsecond time scales following the absorption of UV light. From a common nitro-S1 excited state, the PTs can either undergo excited state intramolecular hydrogen transfer (ESIHT) to an aci-S1 isomer within the singlet state manifold, leading to direct S1 → S0 internal conversion through a conical intersection, or competitive intersystem crossing (ISC) to access the triplet state manifold on time scales of (1.93 ± 0.03) ps and (13.9 ± 1.2) ps for DMNB-Ser and NB-Tyr, respectively. Deprotonation of aci-T1 species to yield triplet anions is proposed to occur in both PTs, with an illustrative time constant of (9.4 ± 0.7) ns for DMNB-Ser. More than 75% of the photoexcited molecules return to their electronic ground states within 8 µs, either by direct S1 → S0 relaxation or anion reprotonation. Hence, upper limits to the quantum yields of photoproduct formation are estimated to be in the range of 13-25%. Mixed DMSO/H2O solvents show the influence of the environment on the observed photochemistry, for example, revealing two nitro-S1 lifetimes for DMNB-Ser in a 10:1 DMSO/H2O mixture of 1.95 ps and (10.1 ± 1.2) ps, which are attributed to different microsolvation environments.

Unraveling the Ultrafast Photochemical Dynamics of Nitrobenzene in Aqueous Solution.

Nitroaromatic compounds are major constituents of the brown carbon aerosol particles in the troposphere that absorb near-ultraviolet (UV) and visible solar radiation and have a profound effect on the Earth's climate. The primary sources of brown carbon include biomass burning, forest fires, and residential burning of biofuels, and an important secondary source is photochemistry in aqueous cloud and fog droplets. Nitrobenzene is the smallest nitroaromatic molecule and a model for the photochemical behavior of larger nitroaromatic compounds. Despite the obvious importance of its droplet photochemistry to the atmospheric environment, there have not been any detailed studies of the ultrafast photochemical dynamics of nitrobenzene in aqueous solution. Here, we combine femtosecond transient absorption spectroscopy, time-resolved infrared spectroscopy, and quantum chemistry calculations to investigate the primary steps following the near-UV (λ ≥ 340 nm) photoexcitation of aqueous nitrobenzene. To understand the role of the surrounding water molecules in the photochemical dynamics of nitrobenzene, we compare the results of these investigations with analogous measurements in solutions of methanol, acetonitrile, and cyclohexane. We find that vibrational energy transfer to the aqueous environment quenches internal excitation, and therefore, unlike the gas phase, we do not observe any evidence for formation of photoproducts on timescales up to 500 ns. We also find that hydrogen bonding between nitrobenzene and surrounding water molecules slows the S1/S0 internal conversion process.

Characterization of the Reversible Intersystem Crossing Dynamics of Organic Photocatalysts Using Transient Absorption Spectroscopy and Time-Resolved Fluorescence Spectroscopy.

Thermally activated delayed fluorescence (TADF) emitters are molecules of interest as homogeneous organic photocatalysts (OPCs) for photoredox chemistry. Here, three classes of OPC candidates are studied in dichloromethane (DCM) or N,N-dimethylformamide (DMF) solutions, using transient absorption spectroscopy and time-resolved fluorescence spectroscopy. These OPCs are benzophenones with either carbazole (2Cz-BP and 2tCz-BP) or phenoxazine/phenothiazine (2PXZ-BP and 2PTZ-BP) appended groups and the dicyanobenzene derivative 4DP-IPN. Dual lifetimes of the S1 state populations are observed, consistent with reverse intersystem crossing (RISC) and TADF emission. Example fluorescence lifetimes in DCM are (5.18 ± 0.01) ns and (6.22 ± 1.27) µs for 2Cz-BP, (1.38 ± 0.01) ns and (0.32 ± 0.01) µs for 2PXZ-BP, and (2.97 ± 0.01) ns and (62.0 ± 5.8) µs for 4DP-IPN. From ground state bleach recoveries and time-correlated single photon counting measurements, triplet quantum yields in DCM are estimated to be 0.62 ± 0.16, 0.04 ± 0.01, and 0.83 ± 0.02 for 2Cz-BP, 2PXZ-BP, and 4DP-IPN, respectively. 4DP-IPN displays similar photophysical behavior to the previously studied OPC 4Cz-IPN. Independent of the choice of solvent, 4DP-IPN, 2Cz-BP, and 2tCz-BP are shown to be TADF emitters, whereas emission by 2PXZ-BP and 2PTZ-BP depends on the molecular environment, with TADF emission enhanced in aggregates compared to monomers. Behavior of this type is representative of aggregation-induced emission luminogens (AIEgens).

Probing the electronic relaxation pathways and photostability of the synthetic nucleobase Z via laser interfaced mass spectrometry.

The photostability of synthetic (unnatural) nucleobases is important in establishing the integrity of new genetic alphabets, and critical for developing healthy semisynthetic organisms. Here, we report the first study to explore the photostability and electronic decay pathways of the synthetic nucleobase, Z (6-amino-5-nitro-2(1H)-pyridone), combining UV laser photodissociation and collisional dissociation measurements to characterise the decay pathways across the region from 3.1-4.9 eV. Photoexcitation across this region produced the m/z 138 ion as the dominant photofragment, mirroring the dominant fragment produced upon higher-energy collisional excitation. Analysis of the ion-yield production curve profile for the m/z 138 ion indicates that it is produced following ultrafast excited state decay with boil off of the OH functional group of Z from the hot electronic ground state. Electronic structure calculations provide physical insight into why this is the dominant fragmentation pathway, since a node in the electron density along the C-OH bond is found for all tautomers of Z. While the dominant decay pathway for Z is consistent with ultrafast excited state decay, we also identify several minor dissociative photochemistry decay pathways, associated with intrinsic photoinstability. The results presented here can be used to guide the development of more photostable synthetic nucleobases.

Drug updates and approvals: 2018 in review.

In 2018, the FDA approved several new drugs for use in primary care. This article highlights the following new drugs: bictegravir, emtricitabine, and tenofovir alafenamide (Biktarvy); doxylamine succinate and pyridoxine hydrochloride (Bonjesta); erenumab-aooe (Aimovig); lofexidine hydrochloride (Lucemyra); tezacaftor and ivacaftor (Symdeko); and tildrakizumab-asmn (Ilumya).

Synthetic methylotrophy: engineering the production of biofuels and chemicals based on the biology of aerobic methanol utilization.

Synthetic methylotrophy is the development of non-native methylotrophs that can utilize methane and methanol as sole carbon and energy sources or as co-substrates with carbohydrates to produce metabolites as biofuels and chemicals. The availability of methane (from natural gas) and its oxidation product, methanol, has been increasing, while prices have been decreasing, thus rendering them as attractive fermentation substrates. As they are more reduced than most carbohydrates, methane and methanol, as co-substrates, can enhance the yields of biologically produced metabolites. Here we discuss synthetic biology and metabolic engineering strategies based on the native biology of aerobic methylotrophs for developing synthetic strains grown on methanol, with Escherichia coli as the prototype.

Molecular cloning, distribution and functional analysis of the NA(V)1.6. Voltage-gated sodium channel from human brain.

We have cloned and expressed the full-length human Na(V)1.6 sodium channel cDNA. Northern analysis showed that the hNa(V)1.6 gene, like its rodent orthologues, is abundantly expressed in adult brain but not other tissues including heart and skeletal muscle. Within the adult brain, hNa(V)1.6 mRNA is widely expressed with particularly high levels in the cerebellum, occipital pole and frontal lobe. When stably expressed in human embryonic kidney cells (HEK293), the hNa(V)1.6 channel was found to be very similar in its biophysical properties to human Na(V)1.2 and Na(V)1.3 channels [Eur. J. Neurosci. 12 (2000) 4281-4289; Pflügers Arch. 441 (2001) 425-433]. Only relatively subtle differences were observed, for example, in the voltage dependence of gating. Like hNa(V)1.3 channels, hNa(V)1.6 produced sodium currents with a prominent persistent component when expressed in HEK293 cells. These persistent currents were similar to those reported for the rat Na(V)1.2 channel [Neuron 19 (1997) 443-452], although they were not dependent on over-expression of G protein betagamma subunits. These data are consistent with the proposal that Na(V)1.6 channels may generate the persistent currents observed in cerebellar Purkinje neurons [J. Neurosci. 17 (1997) 4157-4536]. However, in our hNa(V)1.6 cell line we have been unable to detect the resurgent currents that have also been described in Purkinje cells. Although Na(V)1.6 channels have been implicated in producing these resurgent currents [Neuron 19 (1997) 881-891], our data suggest that this may require modification of the Na(V)1.6 alpha subunit by additional factors found in Purkinje neurons but not in HEK293 cells.