The CFH group, a potential surrogate for the OH group, can act as an unusual hydrogen bond donor, as confirmed by crystallographic, spectroscopic, and computational methods. Here, we demonstrate the bioisosterism of the OH and CFH groups and the important roles of CF-H···O hydrogen bonds in influencing intermolecular interactions and conformational preferences. Experimental evidence, corroborated by theory, reveals the distinctive nature of CFH hydrogen bonding interactions relative to their normal OH hydrogen bonding counterparts.

Fluorescent sensors for mobile zinc have proven valuable for studying complex biological systems. Because these sensors typically bind zinc rapidly and tightly, there has been little temporal control over the activity of the probe after its application to a sample. The ability to control the activity of a zinc sensor in vivo during imaging experiments would greatly improve the time resolution of the measurement. Here, we describe photoactivatable zinc sensors that can be triggered with short pulses of UV light. These probes are prepared by functionalizing a zinc sensor with protecting groups that render the probe insensitive to metal ions. Photo-induced removal of the protecting groups restores the binding site, allowing for zinc-responsive changes in fluorescence that can be observed in live cells and tissues.

Ionic conductivity and membrane capacitance are two foundational parameters that govern neuron excitability. Conventional optogenetics has emerged as a powerful tool to temporarily manipulate membrane ionic conductivity in intact biological systems. However, no analogous method exists for precisely manipulating cell membrane capacitance to enable long-lasting modulation of neuronal excitability. Genetically targetable chemical assembly of conductive and insulating polymers can modulate cell membrane capacitance, but further development of this technique has been hindered by poor spatiotemporal control of the polymer deposition and cytotoxicity from the widely diffused peroxide. We address these issues by harnessing genetically targetable photosensitizer proteins to assemble electrically functional polymers in neurons with precise spatiotemporal control. Using whole-cell patch-clamp recordings, we demonstrate that this optogenetic polymerization can achieve stepwise modulation of both neuron membrane capacitance and intrinsic excitability. Furthermore, cytotoxicity can be limited by controlling light exposure, demonstrating a promising new method for precisely modulating cell excitability.

Biocompatible functional nanomaterials, when integrated into living systems, have the potential to both augment basic biological functions and introduce completely new functions into organisms. Incorporating functional nanomaterials with unique physical properties into living cells has created a new paradigm in synthetic biology, allowing researchers to manipulate and even enhance biology in ways not possible with traditional chemical or genetic modifications. In this review, first, we review the latest developments in interfacing synthetic nanomaterials with organisms at the cellular level, and relevant applications, especially to neuromodulation and augmented photosynthesis. Then, we highlight the need for targeting nanomaterials to specific cells or subcellular destinations within large, multicellular organisms in order to achieve precise control over these systems in a biocompatible manner. In particular, we discuss recent advances in in vivo nanomaterial synthesis and how they can be used to achieve this precise nanomaterial integration. Finally, we introduce genetically-targetable chemical assembly for in situ nanomaterial synthesis as an emerging tool. We discuss the perspectives of novel cell-type-specific biological manipulations by these genetically-targeted methods.