Network of Functional Molecular Containers with Controlled Switchable Abilities

Project Information

NOAH

Grant agreement ID: 765297

DOI

10.3030/765297

Project closed

EC signature date 17 August 2017

Start date 1 April 2018

End date 30 September 2022

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 2 525 640,84

EU contribution

€ 2 525 640,84

Coordinated by

FUNDACIO INSTITUT CATALA D'INVESTIGACIO QUIMICA
Spain

Periodic Reporting for period 2 - NOAH (Network of Functional Molecular Containers with Controlled Switchable Abilities)

Reporting period: 2020-04-01 to 2022-09-30

Summary of the context and overall objectives of the project

NOAH trained early-stage researchers (ESRs) in a multidisciplinary chemical research program within the area of functional molecular containers, encapsulation processes and their applications to end up with a PhD degree.
Breakthrough discoveries in the field of molecular containers are hampered by three main issues: 1) compartmentalisation of research based on different types of containers for synthetic convenience and lack of connection between them; 2) limited knowledge of the basic rules that govern molecular encapsulation; and 3) complexity of the thermodynamic and kinetic characterisation of the inclusion/release processes. To address this problem, NOAH project brought a multimodal network composed of recognised research groups from academia and industry with complementary areas of expertise. The network generated 10 skilled fellows equipped with these diverse skills set to confront challenging and actual encapsulation problems important for academic and industrial sectors. NOAH training network provided them with great variety of scientific attributes, ranging from the experimental organic and inorganic synthesis to computational chemistry. Photo- and electrochemistry, MS/gas-phase chemistry, X-ray diffraction and optical spectroscopy techniques were also included in the scientific formation and development of the recruited ESRs. The trainees also received education in complementary and transferable skills through attendance to local and network-wide dedicated training seminars (e.g. dissemination, communication, organisation,…). The training program included the exposure of the ESRs to chemical research carried out in the non-academic sector by means of full recruitment or short stage secondments in one of the three chemical European companies or the technological centre acting as industrial partners and operating at very different levels: one large company, Covestro, one SME, Biolitec and one technological centre Leitat. ESRs also gained insight in the transfer process of knowledge from academia to industry and other complementary soft-skills.
NOAH research was devoted to the development, characterisation (structural, thermodynamic and kinetic) and transfer to applications of different types of molecular containers. The complementary expertise of NOAH partners on containers’ design, synthesis and characterisation, and transfer to applications together with the identification of a wide library of relevant guests using computational tools ensured the achievement of the full potential of the developed molecular capsules and their exploitation as functional materials for chemical, biological and environmental applications.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the 54 months of duration of the NOAH project (42 + 6) we have synthesised a series of molecular containers using several building blocks (calix[4]pyrroles, calix[4]arene, porphyrins, aromatic multidentate ligands) and using different approaches such as metal coordination, hydrogen bonds, covalent bonds and dynamic covalent bonds. We have equipped the NOAH molecular containers with various functional groups (alkyl chains, ionizable groups, PEG chains...) in order to provide them with solubility in organic or aqueous media. We have been able to insert switchable functionalities in some of our molecular containers (spiropyran and azobenzene units, hemi-indigi groups, pyrazolyl‐pyridine building blocks or triazole moieties) that are addressable with different stimulus (e.g. light, pH or metal).
We have characterised the molecular containers using a full set of characterisation techniques (NMR, IR, UV-Vis, HRMS). We have studied the binding properties of the molecular containers towards different guests, ranging from anions, poly-aromatic guests, and N-oxides, or biologically relevant guests among others. We have characterised the molecular complexes by common characterisation techniques available in the beneficiaries institutions. Moreover, some molecular cages and their corresponding complexes have been characterised in solution using steady-state and time-resolved spectroscopic techniques. Others, have been characterised in the gas phase using advanced mass spectrometry methods.
We have also been able to evaluate the application of the developed containers in different fields such as: coating and adhesive formulations, chemical mediation reactions, trans-membrane anion transport, drug encapsulation or photodynamic therapy and enhaced permeability effect (EPR). Finally, we have been developed a virtual screening tool (HG DYNAusor) to find suitable relevant guests for the molecular containers developed within NOAH. We have already used this tool to quantitatively predict binding energies of different hosts with a series of guest.
We have described some of these results in 16 peer-reviewed scientific publications and NOAH ESRs have presented their research in more than 36 conferences abstracts and posters. In all publications and presentations, the acknowledgement to European Commission for the NOAH project was included. The NOAH outreach activities, NOAH LAB and NOAH NEWS, were set up as dissemination tools for the general public. NOAH LAB outreach suitcases are now available in most NOAH institutions. 4 issues of NOAH NEWS are available at NOAH website. NOAH ESRs have participated in multiple outreach events: European researchers’ night, science fairs, crazy about chemistry, and many outreach events in high schools among others.
COVESTRO submitted 1 patent from the results derived from NOAH project entitled "Nanoencapsulation of metal carboxylate catalysts for polyurethane formulation” 2021, ID30217.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The complementary areas of expertise within the members of the Consortium allowed research innovation beyond the state-of-the-art, including:

1) Development of large synthetic containers with functionalised interiors. These advancements overcome the limited binding based only in shape and size displayed by non-functionalised small cavities.
2) Development of new water-soluble capsular assemblies to enhance the potential applications of the prepared containers in biological applications (e.g. light-controlled transmembrane anion transport).
3) Development of new receptors incorporating stimuli-responsive moieties and polar binding sites. This development has generated new strategies for orthogonal functionalisation.
4) Development of a new tool for quantitative and accurate prediction of guest binding using in-silico screening and molecular modelling. These findings will overcome the usual trial-and-error approach for identifying relevant guests for the designed molecular containers.
5) Advancements in the microencapsulation of polyisocyanates and nanoencapsulation of metal catalysts for applications in coating and adhesive formulations. Patent submitted.
6) New knowledge in mediation of chemical reaction inside molecular containers or other catalytic applications.
7) Development of new photosensitizers with potential appliction in photodynamic therapy.
8) New arene-ruthenium derivatives to be exploited in Enhanced Permeability and retention (EPR) effect

Beside the described research advancements we have trained 10 ESRs that have (or will) become doctors with multidisciplinary and innovative skills. Some of them already found jobs in academia (postdoctoral positions (ESR1, ESR5)) or in industry (ESR8 and ESR9). We also started new scientific collaborations that will continue beyond the project lifetime.

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