Periodic Reporting for period 1 - ReadingMachine (Molecular machine for information reading and catalysis)
Reporting period: 2020-05-01 to 2022-04-30
ReadingMachine project proposed the development of chemically fuelled linear molecular machines capable of active transport of cargo, the read-out information and other sophisticated tasks.
The project intended to build a [2]rotaxane-based molecular machine in which the thread is composed of multiple compartments for the storage of different chiral information. The machine should be able to pump a macrocycle onto the track and directionally transport it from one end to the other by addition of pulses of a chemical fuel. During the transportation process, the macrocycle recognise the information at each station it docks at, performing a non-destructive ‘read-out’ task that can be reported by a circular dichroism (CD) output. By processively transporting the macrocycle, the sequential information of the track should be transcribed into a series of CD signals. The macrocycle reading process ultimately enable the molecular machine to be a ‘smart’ catalyst for the selective synthesis of specific products according to the signal it reads – in a way that is reminiscent of RNA polymerase reading the information from DNA and transcribing it to encode proteins in life.
Three objectives were initially established:
1. Developing a linear molecular machine that can load, transport and release a substrate in a unidirectional manner
2. Developing a ‘Reading Machine’
3. Investigating the catalysis behaviour of the ‘ReadingMachine’
Linear molecular machines consisting of several chirality information stored on the track have been synthesized. The operation by using pulsed of chemical fuel can pump the molecular reader (macrocycle) onto the track, unidirectionally transported it and eventually release it. Along the transportation process, the chirality information can be read out by the macrocycle through a series of CD output.
Progress towards investigating the catalysis behaviour of the ‘ReadingMachine’ was described. Several macrocycles that consist of enantioselective catalytic unit have been synthesised and tested for the catalysis.
Time allocation required to carry out the synthetic work of this project was higher than initially expected. The complex behaviour of these systems forced the iterative redesign and synthesis of model compounds, gradually introducing alterations and testing its efficiency in order to improve operation.
The COVID-19 pandemic also affected the development of the project due to the total shutdown of activities in the University of Manchester from March to July 2020 and the restriction of activities from August 2020 to the end of the action. This unforeseen circumstance occurred in a critical stage of the project, heavily affecting general development and progress.
The project intended to build a [2]rotaxane-based molecular machine in which the thread is composed of multiple compartments for the storage of different chiral information. The machine should be able to pump a macrocycle onto the track and directionally transport it from one end to the other by addition of pulses of a chemical fuel. During the transportation process, the macrocycle recognise the information at each station it docks at, performing a non-destructive ‘read-out’ task that can be reported by a circular dichroism (CD) output. By processively transporting the macrocycle, the sequential information of the track should be transcribed into a series of CD signals. The macrocycle reading process ultimately enable the molecular machine to be a ‘smart’ catalyst for the selective synthesis of specific products according to the signal it reads – in a way that is reminiscent of RNA polymerase reading the information from DNA and transcribing it to encode proteins in life.
Three objectives were initially established:
1. Developing a linear molecular machine that can load, transport and release a substrate in a unidirectional manner
2. Developing a ‘Reading Machine’
3. Investigating the catalysis behaviour of the ‘ReadingMachine’
Linear molecular machines consisting of several chirality information stored on the track have been synthesized. The operation by using pulsed of chemical fuel can pump the molecular reader (macrocycle) onto the track, unidirectionally transported it and eventually release it. Along the transportation process, the chirality information can be read out by the macrocycle through a series of CD output.
Progress towards investigating the catalysis behaviour of the ‘ReadingMachine’ was described. Several macrocycles that consist of enantioselective catalytic unit have been synthesised and tested for the catalysis.
Time allocation required to carry out the synthetic work of this project was higher than initially expected. The complex behaviour of these systems forced the iterative redesign and synthesis of model compounds, gradually introducing alterations and testing its efficiency in order to improve operation.
The COVID-19 pandemic also affected the development of the project due to the total shutdown of activities in the University of Manchester from March to July 2020 and the restriction of activities from August 2020 to the end of the action. This unforeseen circumstance occurred in a critical stage of the project, heavily affecting general development and progress.
WP1
First, investigation on preparation of a linear molecular ratchet that can load, transport and release a substrate in a unidirectional manner had been explored. The employment of dibenzylamine/methyl trizolium moieties as binding units for crown ether based macrocycle effectively provided a driving force for switching the position of the macrocycle along the track; the usage of the hydrazone, disulfide barriers then gave access to the unidirectional transporting the macrocycle along the track in response to acid-base oscillation.
Operation of the molecular ratchet with either sequential addition of trifluoroacetic acid and trimethylamine or trichloroacetic acid as chemical fuel can successfully realize the aim of loading, transporting and releasing a cargo.
WP2
A molecular ratchet with different handedness of dibenzylamine attaching to both sides of the triazolium unit was synthesized. A 2’,2’’-quaterphenyl 26-crown-8 ether was employed for reading out the specific handedness on each binding unit.
Stepwise operation with acid protonated the dibenzylamine, resulting the pumping of the macrocycle onto the track from solution and its binding with the first chiral benzylammonium unit. This led to a unique Circular Dichroism (CD) readout through supramolecular recognition and amplification. Further basification of the system with trimethylamine in presence of disulfide neutralized the benzylammonium moiety, opened the disulfide barrier, locked the hydrazone barrier, drove the movement of the macrocycle to the triazolium moiety. Because of the non-chiral property of triazolium unit, the macrocycle exhibited a non-chiral CD readout. Then the system was acidified again in presence of hydrazine, realizing the macrocycle moving to bind with the last chiral benzylammonium unit. The macrocycle reported an opposite CD readout comparing to the first chiral unit it binds.
Next, another molecular ratchet with same handedness of dibenzylamine was synthesized. Operation with sequential addition of acid and base resulted a similar CD readout when the macrocycle bound with the first and last chiral benzylamine units.
Last, operation with pulses of a chemical fuel can realize the unidirectional transportation of the modified macrocycle on the chiral molecular ratchet and a similar CD readout as the stepwise operation.
Another molecular ratchet with same handedness of dibenzylamine on first and third compartment was synthesized and tested.
WP3
Following the developments made in WP1 and WP2, the investigation of ’read-out’ information directed conformation changes of macrocycle for catalysis was explored. A model of modified macrocycle employed the phosphine ligand and amide linker was synthesized and used for transition-metal-catalysed asymmetric synthesis. The unique point chiral information of each unit on the track can define the conformation of the macrocycle in different way, leading to the opposite helicity of the bisphophine ligand and spatial difference between the two phosphine groups, which then exhibit enantioselective preferences. At the conclusion of the project, tests for the catalysis are being carried out.
Dissemination and outreach activities envisioned during the project were highly affected due to the COVID-19 pandemic global situation.
First, investigation on preparation of a linear molecular ratchet that can load, transport and release a substrate in a unidirectional manner had been explored. The employment of dibenzylamine/methyl trizolium moieties as binding units for crown ether based macrocycle effectively provided a driving force for switching the position of the macrocycle along the track; the usage of the hydrazone, disulfide barriers then gave access to the unidirectional transporting the macrocycle along the track in response to acid-base oscillation.
Operation of the molecular ratchet with either sequential addition of trifluoroacetic acid and trimethylamine or trichloroacetic acid as chemical fuel can successfully realize the aim of loading, transporting and releasing a cargo.
WP2
A molecular ratchet with different handedness of dibenzylamine attaching to both sides of the triazolium unit was synthesized. A 2’,2’’-quaterphenyl 26-crown-8 ether was employed for reading out the specific handedness on each binding unit.
Stepwise operation with acid protonated the dibenzylamine, resulting the pumping of the macrocycle onto the track from solution and its binding with the first chiral benzylammonium unit. This led to a unique Circular Dichroism (CD) readout through supramolecular recognition and amplification. Further basification of the system with trimethylamine in presence of disulfide neutralized the benzylammonium moiety, opened the disulfide barrier, locked the hydrazone barrier, drove the movement of the macrocycle to the triazolium moiety. Because of the non-chiral property of triazolium unit, the macrocycle exhibited a non-chiral CD readout. Then the system was acidified again in presence of hydrazine, realizing the macrocycle moving to bind with the last chiral benzylammonium unit. The macrocycle reported an opposite CD readout comparing to the first chiral unit it binds.
Next, another molecular ratchet with same handedness of dibenzylamine was synthesized. Operation with sequential addition of acid and base resulted a similar CD readout when the macrocycle bound with the first and last chiral benzylamine units.
Last, operation with pulses of a chemical fuel can realize the unidirectional transportation of the modified macrocycle on the chiral molecular ratchet and a similar CD readout as the stepwise operation.
Another molecular ratchet with same handedness of dibenzylamine on first and third compartment was synthesized and tested.
WP3
Following the developments made in WP1 and WP2, the investigation of ’read-out’ information directed conformation changes of macrocycle for catalysis was explored. A model of modified macrocycle employed the phosphine ligand and amide linker was synthesized and used for transition-metal-catalysed asymmetric synthesis. The unique point chiral information of each unit on the track can define the conformation of the macrocycle in different way, leading to the opposite helicity of the bisphophine ligand and spatial difference between the two phosphine groups, which then exhibit enantioselective preferences. At the conclusion of the project, tests for the catalysis are being carried out.
Dissemination and outreach activities envisioned during the project were highly affected due to the COVID-19 pandemic global situation.
‘Read-out’ processes are essential to life, and typical examples including code transfer from DNA to RNA or from RNA to the amino acid sequence in the polypeptide chain implemented by enzymes. This work is the first example of constructing a fuelled molecular machine for implementation of the reading task in a ‘non-destructive’ way. By transporting the macrocycle through the track, the molecular machine acts as a first generation mimic of RNA polymerase that perform enantioselective synthesis by the track information (chirality) directed macrocycle conformation changes. The use of this ‘non-destructive’ reading machine would be a landmark in learning how to design and construct increasingly advanced synthetic molecular machines and provide new ideas and possibilities for their use, for example ‘restorage’ and ‘replication’ of stored information, and ultimately use such molecular machine to write (i.e. synthesize) sequence information as it is reading from the track.