Welcome to the Research Group of Henry Dube!

Molecular Machines

Molecular machines represent the quintessential realization of Feynmans 1959 vision – to fill the “plenty of room at the bottom” with intricate functions. We have contributed to this rapidly evolving field by generating fast and visible light driven molecular motors that are highly promising for applications not tolerant of damaging UV light or high temperatures.After developing new synthetic methods for their manufacturing and gaining control over their maximum rotation speeds2 we recently provided a comprehensive mechanistic picture of their mode of action.3 From these studies crucial factors to influence their efficiencies and future design opportunities could be gleaned. 

Our current efforts are directed at applications in integrated molecular machines and implementation of our motors into more complex environments. In this regard we have achieved transmission of motor motion unto passive biaryl axes4 and even acceleration of their motions by several orders of magnitude.5

In very recent breakthroughs in our laboratory we achieved the development of two entirely new types of molecular motors. A photon-only driven motor works without thermal ratcheting in the ground state and is powered by three consecutive light-induced steps. Because of this unique mechanism a reverse temperature dependency of its efficiency is observed, i.e. this motor becomes faster at lower temperatures instead of slower.6 Our newest motor development enables more complex directional motions than the hitherto possible linear or circular trajectories. Powered by green light the molecular motor undergoes an eight-shape motion, which is fully directional.7 These developments will open up new avenues for molecular machines and their applications in the near future.

1.  Nat. Commun. 2015, 6, 8406.

2.  Angew. Chem. Int. Ed. 2017, 56, 14536.

3.  J. Am. Chem. Soc. 2018, 140, 5311.

4.  Angew. Chem. Int. Ed. 2018, 130, 11231.

5.  Angew. Chem. Int. Ed. 2020, 132, 5730.

6.  J. Am. Chem. Soc. 2018, 140, 16442.

7.  Nat. Commun. 2019, 10, 4449.


Functional Supramolecular Systems

In this research line we develop and study functional supramolecular systems that can be controlled in their properties by external stimuli. We strive to go beyond the sole establishment of molecular recognition processes and implement responsive elements for smart and emerging behavior.

To this end we have created different photoresponsive receptor1 and molecular tweezers motives,2 which we can reversibly switch between high and low affinity states using visible light signals. In a recent effort we were able to elicit a complex and dynamic guest relocation in solution by realizing a new concept: “simultaneous complementary photoswitching”.3 Two complementary substituted molecular tweezers respond to the same wavelength of irradiation in opposite manners. If the first tweezers gain binding affinity the second tweezers lose it at the same time, leading to relocalization of the guest from one host to the other. At a different wavelength of light irradiation the binding affinities and guest residing can be reversed. Only minimal signaling is needed to obtain a multifaceted supramolecular behavior as the result.

Most recently we started to merge molecular machines with supramolecular chemistry. Using a molecular motor as photoswitchable receptor for hydrogen-bonding organocatalysts the activity of the latter can be made light responsive. In a relay process the organocatalyst can be captured and released from the motor, altering its catalytic activity in a Michael addition reaction. Motor operation thus remote controls catalysis without direct interference.4

1.  Chem. Eur. J. 2016, 22, 16433.

2.  Chem. Sci. 2021, 12, 3651.

3.  Nat. Commun. 2018, 9, 1456.

4.  J. Am. Chem. Soc. 2020, 142, 45, 19300.



One core activity in our research concerns chromophore design and mechanistic studies to develop new photoresponsive molecules with unique property profiles. Our long-term goal is gaining absolute control over light-induced molecular motions enabling full spatial and temporal resolution of nano-, micro-, and macroscopic properties.

Focusing on the underexplored class of indigoid photoswitches1 we have established specific molecular designs, which allow us to evoke a range of distinctive bond rotations by irradiation and directly prove them experimentally. Using simple means, like solvent polarity or temperature, different types of such rotations can be interchanged within the same molecule providing exquisite control over multiple molecular motions. Examples are polarity dependent single or double-bond rotation in donor-substituted hemithioindigo2 or the long elusive hula twist, which we evidenced unambiguously in an axially chiral molecular setup.3 Apart from providing unprecedented insights into fundamental photochemical mechanisms these molecular systems possess especially high potential for the construction of unique future nanomachinery.

In a second research line we are developing highly efficient bistable photoswitches with red light responsiveness, which are interesting for a variety of applications ranging from material sciences to biology and photopharmacology. Particularly impressive performances are given by donor-substituted hemiindigo chromophores allowing photoswitching at the biooptical window with half-lives of the metastable forms reaching >1000 years at ambient temperatures.4,5

Our newest addition to molecular photoswitches is the long known chromophore indirubin, which is rendered into a proficient photoswitch by alkylation. In a supramolecular approach selective hydrogen bonding to the E isomer allows to invert indirubins photochromism and photoswitching in both directions can now be elicited by two different shades of red light.6

1.  Acc. Chem. Res. 2018, 51, 1153.

2.  J. Am. Chem. Soc. 2016, 138, 12219.

3.  Nat. Commun. 2018, 9, 2510.

4.  J. Am. Chem. Soc. 2017, 139, 15060.

5.  J. Am. Chem. Soc. 2018, 140, 13558.

6.  J. Am. Chem. Soc. 2021, accepted.


Chemical Biology

In this research line we develop advanced chemical biology tools for precision regulation of biological processes. Our first approach delivered blue light control over the cell cycle and apoptosis of cancer cells in collaboration with the Zanin lab. To this end we have photocaged the versatile proteasome inhibitor MG132 directly at its reactive aldehyde function keeping the oxidation state unchanged. Upon caging bioactivity is lost and cells proliferate normally. Irradiation releases the inhibitor at a given time and leads to metaphase arrest of the cells. Prolonged exposure causes the apoptosis pathway to be activated and blue light treated cells die. Our light-activated biomolecular tool therefore enables spatial-temporal control of cell fate and was further shown to be compatible with live-cell imaging methods.1

1.   Angew. Chem. Int. Ed. 2021, 60, 1187.