Hydrazone-Based Switches: Communication, Recognition, Transport, and Environmental Effects

Author

Heyifei FuFollow

Author ORCID Identifier

https://orcid.org/0000-0003-4067-6067

Date of Award

Spring 5-14-2025

Document Type

Thesis (Ph.D.)

Department or Program

Chemistry

First Advisor

Ivan Aprahamian

Abstract

Biological systems achieve intricate control over processes such as signal transduction and ion transport through complex intermolecular communication networks. Replicating such dynamic control over synthetic supramolecular systems is a grand challenge. This thesis uses chemically and photochemically activated hydrazone-based switches to try and emulate similar intricate allosteric regulation in synthetic supramolecular systems.

First, we illustrate the conceptual foundation for both chemically and light-activated molecular switches, positioning hydrazones as a robust and tunable platform. Building on this foundation, we developed a hierarchical multistep switching cascade: a Zn(II)-initiated metal and proton relays that propagate a reversible signal between two different hydrazone units via coordination-coupled deprotonation (CCD). A single chemical input thereby drives intermolecular communication, mirroring the layered logic of biological signaling pathways.

The centerpiece of this thesis is a light-driven molecular anion pump employing a trimeric hydrazone receptor to actively transport chloride ions against a concentration gradient. Reversible E/Z photoisomerization modulates the receptor’s binding affinity, enabling directional Cl^- uptake and release. This design converts light energy into chemical work, achieving one of the first synthetic anion pumps and underscoring the power of hydrazone switches in active, out-of-equilibrium supramolecular systems.

Finally, we introduce a novel class of photoswitches based on BF₂-coordinated hydrazones. These so-called azo-BF₂ switches, while highly useful in visible and near-infrared applications, face a stability challenge in the solution-state. We studied how subtle π-system modifications and solvent polarity govern their switching properties, stability, and reactivity. Mechanistic pathways such as intramolecular 1,2-BF₂ shift and solvent-induced solvolysis are elucidated, informing strategies to enhance photoswitch performance.

Original Citation

1. Fu, H.; Pramanik, S.; Aprahamian, I. Metal and Proton Relay-Controlled Hierarchical Multistep Switching Cascade. J. Am. Chem. Soc. 2023, 145, 19554–19560.

2. Shao, B.; Fu, H.; Aprahamian, I. A Molecular Anion Pump. Science 2024, 385, 544–549.

Recommended Citation

Fu, Heyifei, "Hydrazone-Based Switches: Communication, Recognition, Transport, and Environmental Effects" (2025). Dartmouth College Ph.D Dissertations. 343.
https://digitalcommons.dartmouth.edu/dissertations/343