The Art of Building Small from molecular switches to motors

Ben Feringa Stockholm december 8th, 2016 Bioinspired Motion the early days fascinated by…

…but no copy or mimic!

17th of December 1903 at Kitty Hawk

heading for…..? The Art of Building Small

Chemical Synthesis Nano Macro

Natural Robot Artifical Robot

± 24 nm = ± 2 m 0.000000024 m effect of length scales soft hard Low Reynolds number Brownian motion Biomolecular Machines Ribosome Bio-Nanomotors Rotary Motor protein synthesis transport – muscle function transport-catalysis

Bacterial Flagellar Motor Optical Switching propulsion Information Molecular Nanoscience molecular light switch

0 1 Optical Molecular Switch

Binary System at the Molecular Level

S S

365 nm

435 nm O I Me2N NO2 Me2N NO2 S S

(M)-cis (P)-trans

Information Storage

Non-destructive read-out

Left (0) Right (1) Potential of Molecular Nanotechnology

Molecular Electronics

Storage capacity of one CD: 1.125.000.000 MB = > 240 years of music Challenges from Molecules to Dynamic Molecular Systems Responsive Materials out of Equilibrium

Self-assembly ? Smart Drugs Trigger & Response ? Motion ?

Soft Robotics Cell MEMBRANE Self-Assembly

amphiphile

O O O HO O

S S

HO O O O O

Polar Headgroup Aromatic Core Apolar Tail

S

Molecular switch R photo- and electro-chemical switching R

S Nanotube by self-assembly

100 nm Controlling the disassembly of a Nanotube with light Nano-channel: trigger & response

open & close with light ?? Mechanosensitive Channel from E. coli bacterium

3-4 Nm channel in open state Molecular Device

MscL channel protein

Liposome

O2N

UV nm) (366 O N O NO2 Vis (>460 nm) N O R O O R O Switch

Controlled drug delivery Self-healing materials inactive

Target Smart Pharmaceuticals therapeutic action precisionHigh in light signal awith on Switchingmedicine a (off) 0 (on) 1 Bacterial Resistance Cancer Treatment one of humanity’s chemotherapy “ticking time-bombs” http://www.who.int/mediacentre/factsheets/fs194/en/ http://www.who.int/cancer/en/ Photocontrolled Antibiotic

O OH OH O O N O N

N N N O N O 0 1 (off) (on)

No resistance build-up Control biofilm formation Photocontrolled Chemotherapeutic Agent Bortezomib

O OH On the market (US; 2003) for the H N N B treatment of mantle cell cancer N OH H O and multiple myeloma N

Avoiding severe side-effects in chemotherapy

© Simon Jarratt/Corbis Photopharmacology 0 1 (off) (on)

Triggering activation with non-invasive light signal

Response Target Spatio-temporal precision in action

Smart Pharmaceuticals Challenges: near-infrared light imaging > drug activation From Switches to Motors

Molecular Motor Meeq Meax > 280 nm

Meax Meeq

stable (P,P)-trans unstable (M,M)-cis

Meax Meeq > 280 nm

1977 Meeq 2006 Meax

unstable (M,M)-trans (PhD thesis, p 61) stable (P,P)-cis Unidirectional First electric car 1999 First synthesis of molecular motor `to Stockholm Unidirectional Overcrowded alkene controlled 2016 molecular motor liquid crystals

1991 2005 2011 Chiroptical Unidirectional Molecular nanocar Overcrowded alkene Motor on a Powered translational switch surface motor on surface Man’s Motor vs. Nature’s Motor

Motor ATP - ase

Molecular Motor

How to control rotary motion? in the nanoworld How to control left or right? My Teachers and Hero’s Jacobus van ‘t Hoff Hans Wijnberg

Stereochemistry

mirror image symmetry “a signature of life” Mirror Image

Breaking Symmetry Unidirectional Rotary Molecular Motor

Powered by Light DEFINITION: A rotary motor is a device that is able to convert energy input into controlled, directional, rotary motion in a continuous fashion REQUIREMENTS:  Controlled Motion  Consumption of Energy  Directional Movement  Repetitive (Continuous) Process

Size: a power-stroke motor 1 nanometer Molecular Motor powered by light

fast slow slow

fast Responsive Catalysts dynamic control of chiral space using a molecular motor product R,S R S chirality

multitasking organo-catalyst sequence control Second Generation Molecular Motor

Molecular Design enhancing the speed

from to 1 rotation/hour more than 10 million rotations/sec Control of Motion Molecular dynamics & length scales Mesoscopic surfaces & catalysts micro-objects & droplets

Macromolecular Nano polymer helicity single molecule movement Rotation of a micro object Molecular motor 1nm

Glass rod, 5 x 28 µm Design of Molecular Motors on Surfaces

S

Me

S O O

(CH2)8 (CH2)8 SH SH

Target Motor Molecule

30

20

10

0 CD (mdeg) CD -10

hν>280 nm∆ hν365 nm ∆ hν365 nm ∆ hν365 nm ∆ -20 0 2 4 6 8 Responsive Surfaces

Molecular Car

0.000000002 meter 2 meter

Four-wheel drive Four Wheel Drive Molecular Car

Nano Car How to convert rotary motion into translational motion??? Single molecule motion!!! Molecular Car Single Molecule Nano Car on Surface Autonomous Propulsion System

Chemical Catalysis

Glucose as fuel ? Fantastic Voyage Nano-Swimmer

Fuel: sugar

Applications: roving sensors delivery systems

100 nm micro-nano-robots Nanorobots, science or science fiction

“The best way to predict the future is to invent it.“ Alan Kay The Art of Building Small N programming molecules responsive & adaptive functions motion dynamic systems

Perspective Information systems Responsive materials Smart surfaces 0 1 Self-healing materials Delivery systems Precision therapeutics Adaptive catalysts Roving sensors NanoEnergy converters Soft-robotics ...... Acknowledgment

generations students & co-workers, colleagues & staff, collaborators, mol machine comm, family

AC Cope Foundation Leonardo da Vinci “Where Nature finishes producing its own species man begins,with the help of Nature, to create an infinity of species”

Imagine the unimaginable