Carbon Nanomaterial Fluorescent Probes and Their Biological Applications.

Fluorescent carbon nanomaterials have broadly useful chemical and photophysical attributes that are conducive to applications in biology. In this review, we focus on materials whose photophysics allow for the use of these materials in biomedical and environmental applications, with emphasis on imaging, biosensing, and cargo delivery. The review focuses primarily on graphitic carbon nanomaterials including graphene and its derivatives, carbon nanotubes, as well as carbon dots and carbon nanohoops. Recent advances in and future prospects of these fields are discussed at depth, and where appropriate, references to reviews pertaining to older literature are provided.

Catalytic Enantioselective Birch-Heck Sequence for the Synthesis of Phenanthridinone Derivatives with an All-Carbon Quaternary Stereocenter.

Novel phenanthridinone analogues with an all-carbon quaternary stereocenter have been enantioselectively synthesized using the Birch-Heck sequence. Flat phenanthridinone structures have extensive bioactivity but consequently also suffer from poor therapeutic selectivity. The addition of a quaternary center to the phenanthridinone skeleton has the potential to generate more complex analogues with improved selectivity. Unfortunately, no general synthetic pathway to such derivatives exists. Herein we report a four-step process that transforms inexpensive benzoic acid into 22 different quaternary carbon-containing phenanthridinone analogues with a variety of substituents on all three rings: alkyl groups at the quaternary center; methyl, methoxymethyl, or para-methoxybenzyl on the amide nitrogen; and halogen and methyl substituents on the aryl ring. Good to very good enantioselectivity was demonstrated in the key intramolecular desymmetrizing Mizoroki-Heck reaction. Transformations of the Heck reaction products into molecules with potentially greater therapeutic relevance were also accomplished.

Visualizing synaptic dopamine efflux with a 2D composite nanofilm.

Chemical neurotransmission constitutes one of the fundamental modalities of communication between neurons. Monitoring release of these chemicals has traditionally been difficult to carry out at spatial and temporal scales relevant to neuron function. To understand chemical neurotransmission more fully, we need to improve the spatial and temporal resolutions of measurements for neurotransmitter release. To address this, we engineered a chemi-sensitive, two-dimensional composite nanofilm that facilitates visualization of the release and diffusion of the neurochemical dopamine with synaptic resolution, quantal sensitivity, and simultaneously from hundreds of release sites. Using this technology, we were able to monitor the spatiotemporal dynamics of dopamine release in dendritic processes, a poorly understood phenomenon. We found that dopamine release is broadcast from a subset of dendritic processes as hotspots that have a mean spatial spread of ≈ 3.2 µm (full width at half maximum [FWHM]) and are observed with a mean spatial frequency of one hotspot per ≈ 7.5 µm of dendritic length. Major dendrites of dopamine neurons and fine dendritic processes, as well as dendritic arbors and dendrites with no apparent varicose morphology participated in dopamine release. Remarkably, these release hotspots co-localized with Bassoon, suggesting that Bassoon may contribute to organizing active zones in dendrites, similar to its role in axon terminals.

To form the vast and complex network necessary for an organism to sense and react to the world, neurons must connect at highly specialized junctions. Individual cells communicate at these 'synapses' by releasing chemical signals (or neurotransmitters) such as dopamine, a molecule involved in learning and motivation. Despite the central role that synapses play in the brain, it remains challenging to measure exactly where neurotransmitters are released and how far they travel from their release site. Currently, most tools available to scientists only allow bulk measurements of neurotransmitter release. To tackle this limitation, Bulumulla et al. developed a new way to measure neurotransmitter release from neurons, harnessing a technique which uses fluorescent nanosensors that glow brighter when exposed to dopamine. These sensors form a very thin film upon which neurons can grow; when the cells release dopamine, the sensors 'light up' as they encounter the molecule. Dubbed DopaFilm, the technology reveals exactly where the neurotransmitter comes from and how it spreads between cells in real time. In particular, the approach showed that dopamine emerges from 'hot spots' at specific sites in cells; it also helped Bulumulla et al. study how dopamine is released from subcellular compartments that have previously not been well characterized. Improving the sensors so that the film could detect other neurotransmitters besides dopamine would broaden the use of this approach. In the future, combining this technology with other types of imaging should enable studies of individual synapses with intricate detail.

Catalytic Enantioselective Birch-Heck Sequence for the Synthesis of Tricyclic Structures with All-Carbon Quaternary Stereocenters.

A new enantioselective desymmetrizing Mizoroki-Heck reaction is reported. The process affords high yields and enantioselectivities of tricyclic structures containing all-carbon quaternary stereocenters. The substrates for the reaction are efficiently synthesized from Birch reduction-alkylation of benzoic acid and benzoate esters.