Molecular Pliers
Do the Twist

Protein-based molecular machines play a wide array of roles in the support of life in living organisms. A number of man-made molecular machines have been invented, but as yet it has not been possible to incorporate the conversion/ transmission of molecular motion into the design.

Now, however, our research team at the University of Tokyo has succeeded in creating a molecular machine that exhibits this kind of mechanism. Furthermore, we used this machine to physically move another molecule, becoming the first to do so.

The molecular machine we developed is called a "light-driven molecular pliers." Our molecular pliers is based on the design of the light-driven molecular scissors we had previously developed, which was a tool that opened and closed like a scissors when irradiated with light.

In both machines, we use azobenzene as the drive portion. In response to light, azobenzene undergoes trans-cis isomerization (photoisomerization). The two azobenzene isomers differ in length. The azobenzene molecule is attached to ferrocene, which serves as the pivot for the scissors' blades or pliers' jaws.

In our light-driven molecular pliers, the shortening and lengthening of the azobenzene molecule is converted to a rotational or pivotal movement where it is connected to the ferrocene portion. Ultimately, the molecular machine is designed to open and close like a pair of jaws.

For the jaws themselves, we used the metal complex zinc porphyrin, a molecular compound based around a metal atom. Zinc porphyrin easily interacts with nitrogenous bases such as amines, forming coordination bonds. Thus, the molecular pliers "grasps" guest compounds such as amines with these bonds.

At this point in the project, our team realized if we could manipulate the distance between the two zinc porphyrin jaws, we could manipulate the three-dimensional structure of guest molecules that interact with zinc porphyrin. In other words, could not our molecular machine reproduce the grasping and turning action of a pair of pliers?

In the ferrocene portion of the molecular pliers (1), two enantiomers are expressed which have a left hand/right hand relationship. Consequently, we were able to track changes in the three-dimensional structure using circular dichroism (CD) spectroscopy, a specific type of spectrum measurement. In our experiments, we chose biisoquinoline (2), which has highly coordinating nitrogen atoms and which undergoes rotational motion, as the guest molecule. Because in solution biisoquinoline adopts a rotational movement, freely spinning around and around, it doesn't exhibit a CD signal. When in association with the molecular pliers, however, biisoquinoline's rotational motion halts. In other words, when twisted in the jaws of the molecular pliers, the biisoquinoline can no longer spin and the CD signal reflecting this state can be monitored.

When we added biisoquinoline to the molecular pliers (trans-1) prior to exposure to light, CD originating from the biisoquinoline was expressed, strongly indicating that it was being held in association with the trans-1.

A different analysis showed that trans-1 and biisoquinoline were strongly linked. When we irradiated trans-1 azobenzene in association with biisoquinoline with ultraviolet light (350 nm), it under went isomerization, converting to the shorter cis-1 isomer. Interestingly enough, when the trans-1 isomer underwent isomerization, the CD signal of the biisoquinoline in association with it disappeared. This suggests that isomerization of trans-1 caused the biisoquinoline to become essentially flat. Moreover, when the sample is then re-exposed to visible light (>400 nm) it again undergoes isomerization and reverts back to the trans-1 isomer. In other words, the trans-1/cis-1 isomerization process is reversible (Figure 1).

The key point here is whether the biisoquinoline is released from the grasp of the molecular pliers during the isomerization process. In fact, we found that both the cis-1 and the trans-1 isomers tightly grasped the biisoquinoline molecule. Furthermore, by using nuclear magnetic resonance spectrum measurements, we were able to estimate molecular dynamics and discovered that disassociation of biisoquinoline from trans-1 and cis-1 occurred on a scale of 0.6 milliseconds and 0.2 milliseconds, respectively. Ordinarily, photoisomerization of azobenzene is known to occur on a much faster scale of picoseconds, suggesting that the guest molecules are rarely released from the jaws of the pliers during the light reaction. In other words, this clearly shows that the molecular pliers holds and twists the biisoquinoline (Figure 2).

Thus, in our work, we succeeded in using a light-driven molecular pliers to physically twist the guest biisoquinoline molecule. This is the first example in the field of molecular machines of a motion being transmitted from one molecule to another and is a major step towards the design of molecular robots with complex functions.