RADBOUD UNIVERSITY NIJMEGEN RESEARCH PROPOSAL HONOURS ACADEMY FNWI The molecular monorail Authors: Robert BECKER Nadia ERKAMP Supervisor: Marieke GLAZENBURG Prof. Thomas BOLTJE Evert-Jan HEKKELMAN Lisanne SELLIES May 2017 Contents 1 Details 2 1.1 Applicants . .2 1.2 Supervisor . .2 1.3 Keywords . .2 1.4 Field of research . .2 2 Summaries 3 2.1 Scientific summary . .3 2.2 Public summary . .3 2.3 Samenvatting voor algemeen publiek . .3 3 Introduction 5 4 Background 8 4.1 The Feringa motor . .8 4.2 The ring molecule . .9 4.3 Threading of the track . 11 4.4 The track polymer . 12 5 Methods 14 5.1 Optical trapping . 14 5.2 Detection . 15 5.3 Synthesis . 16 5.3.1 Ring.................................... 16 5.3.2 Track . 17 6 Future applications 18 6.1 Further shrink down lab-on-a-chip approach . 18 6.2 Lab-on-a-chip approach in health care: Point-of-care testing (POCT) . 18 1 1 Details 1.1 Applicants Robert Becker - Biology Evert-Jan Hekkelman - Physics & Nadia Erkamp - Chemistry Mathematics Marieke Glazenburg - Physics Lisanne Sellies - Chemistry 1.2 Supervisor Name: Thomas Boltje Telephone: 024-3652331 Email: [email protected] Institute: Synthetic Organic Chemistry Radboud University Nijmegen 1.3 Keywords Nanomachine, Feringa, polymer, porphyrin, FRET 1.4 Field of research NWO division: Chemical Sciences [CW] Code Main field of research 13.20.00 Macromolecular chemistry, polymer chemistry Other fields of research 13.30.00 Organic chemistry 13.50.00 Physical chemistry 12.20.00 Nanophysics/technology 14.80.00 Nanotechnology 2 2 Summaries 2.1 Scientific summary In this proposal we present the design for a new kind of nanomachine. A nanoma- chine is an assembly of a distinct number of molecular components that are designed to perform machinelike movements as a result of an appropriate external stimula- tion. The currently existing nanomachines have at least one of the following disad- vantages: they are either slow, non-autonomous or move in an unpredictable direc- tion. Some even suffer from a combination of these. In our design we couple an autonomous motor to a ring that moves along a track. The motor of the Nobel Prize winner Feringa is used to make the nanomachine move. A ring-shaped molecule will be designed and the motor of Feringa will be bound to it in such a manner that it produces a propulsive force. Furthermore, the ring consists of two porphyrin rings and some bulky groups to prevent it from collapsing or fold- ing. The ring can move along a track made of alternating benzene rings and triple bonds, containing some fluorescent BODIPY groups. A BODIPY group is also present on the ring, opening up the possibility for FRET as detection method. In the future, the proposed nanomachine may be used for the active transport of cargo. This in turn may boost the development of a microfluidic lab-on-a chip sys- tem, where it would be used to transfer molecules from one fluid stream to another. Some microfluidic lab-on-a chip systems find application in health care. 2.2 Public summary Imagine an everyday utensil like a car or a switch and make it a billion times smaller: you now have a nanomachine. In the past years, there has been impressive process in the development of these tiny molecular devices, among which, perhaps the most appealing to the imagination, an actual four-wheel drive nanocar. Current molecular machines however still struggle with basic issues like speed and controllability. This research proposes the design of a new nanomachine to solve exactly these issues: a molecular ‘monorail’ consisting of a ring, driven by rotating propellers, sliding along a track in one direction. In the future, this design may be useful in medical applica- tions, e.g. the transport of substances in miniature laboratoria. 2.3 Samenvatting voor algemeen publiek Neem een alledaags gebruiksvoorwerp zoals een auto of een schakelaar en maak dit een miljard keer kleiner: dit is het terrein van de nanomachines. De laatste jaren is er een indrukwekkende vooruitgang zichtbaar in de ontwikkeling van deze minis- cule moleculaire apparaatjes, met als meest tot de verbeelding sprekende doorbraak 3 het nano-autootje van de Groningse Ben Feringa. Toch hebben huidige moleculaire machines nog vaak problemen met onder andere snelheid en bestuurbaarheid. Dit onderzoek stelt het ontwerp voor van een nieuwe nanomachine die deze proble- men oplost: een ‘moleculaire monorail’, bestaande uit een ring, aangedreven door draaiende propellers, die in één richting over een spoor glijdt. In de toekomst zou dit ontwerp toepassingen kunnen vinden in de medische wereld, bijvoorbeeld voor het transporteren van stoffen in miniatuur laboratoria. 4 3 Introduction In 2016, the Nobel Prize in chemistry was awarded to three independently operat- ing researchers, Jean-Pierre Sauvage, Sir J. Fraser Stoddart and Bernard L. Feringa [1]. Each of them made a contribution to a relatively new area of research that has an enormous potential: the development of molecular motors. A molecular motor can be briefly defined as “an assembly of a distinct number of molecular components that are designed to perform machinelike movements (out- put) as a result of an appropriate external stimulation (input)” [2]. The Nobel Prize winner Feringa designed and built such a device: a molecular propeller. This molecule consists of a rigid stator, an axle and a rotor blade. When exposed to UV light, the ro- tor will perform consistent and unidirectional rotational movement [3]. Combining four of these motors led to perhaps even his biggest achievement: his design of a ‘nanocar’, illustrated in figure 1 [4]. One can clearly see the similarities with regular sized cars; Feringa’s nanocar is essentially just a very basic downscale of the macroscopic world. Section 4.1 later on in this proposal will pay elaborate at- tention to his work. Aside from Feringa’s motor, various other kinds of molecular motors have been developed over the years. An ex- ample of this the recent development of autonomously moving microparticles [5]. These particles, or stomatocytes, were able to move through a liquid due to a reaction with hydrogen peroxide, catalysed by the platinum they were loaded with. The oxygen bubbles produced in the process deliver the propulsive force. The stoma- tocytes are capable of reaching relatively high velocities. However, they move rather randomly through the fluid. Motors that do have this directionality are synthetic walkers, DNA walkers for example. DNA walkers are made en- Figure 1: Operation of Feringa’s nanocar [4] tirely of DNA and consist of little more . than two legs propagating along a DNA track by hybridization with DNA fuel strands [6]. This ensures the directional move- 5 ment, but the walkers are often extremely slow in their progress. Furthermore, most DNA walkers require periodic addition of fuel strands, whereas a more autonomous approach (i.e. no need for active chemical fuel addition) would be preferable. The proposed research is aimed at finding solutions to exactly the three issues il- lustrated by the examples above: directionality, speed and autonomy. To achieve this, existing elements will be combined and improved, inspired by the achievements mentioned in the section above. Together this will form an attempt at solving the im- portant challenges in the area mentioned above and coming a step closer to fully functioning, autonomous nanomachines. Figure 2: Spatial impression of the proposed nanomachine. The motor molecules are indicated in green, the ring in blue, the track in purple, the bulky groups by the black circles and the fluorescent BODIPY groups by the red circles. 6 All of the above led to the following research question: How to build an autonomous and unidirectional nanomachine with a high speed? A sketch of the proposed design is illustrated in figure 2. In this design, the motor molecules (green) are incorporated in a ring (blue) that will be threaded onto a track (purple polymer), allowing it to move in only one dimension. Propulsion by the mo- tor molecules will yield the desired speed and autonomy. 7 4 Background 4.1 The Feringa motor No nanomachine is complete without a means of doing work, and Feringa’s motor is one of the most effective ways to achieve work in a rotational fashion. Its spectacular properties and successful track record has made this the motor of choice in this pro- posal. The motor consists of a so-called ‘stator’ and a ‘rotor’, connected by a double car- bon bond. While different versions do exist, they all operate in the same manner (see figure 3). An absorbed photon causes a cis-trans isomerization in the rotor, af- ter which the molecule finds itself in an unstable form. The motor reaches a stable form by thermal helix inversion, which results in a 180± rotation. When another pho- ton hits the molecule, this process repeats itself. That way the motor keeps rotating in the same direction when illuminated constantly [7] [8]. The motion can only be performed in one direction because the chiral carbon atom at the back of the rotor dictates which way the rotor turns if a photon is absorbed. Changing this atom’s chi- rality will cause the motor to turn the other way around. [10] Figure 3: All steps in the process of turning on which the Feringa motor is based. The difference between various versions of this particular machine is the structure of the stator. A conformational change in the stator greatly influences the rate at which the thermal helix inversion takes place, researched in depth by the Feringa group [9] They found that a certain version of Feringa’s motor can achieve a rotational speed of 3 MHz [9].