Understanding Crystal Polymorph Control in Confinement using In-situ TEM

Informations projet

PolyTEM

N° de convention de subvention: 885795

DOI

10.3030/885795

Projet clôturé le 2 Août 2021

Date de signature de la CE 9 Mars 2020

Date de début 9 Mars 2020

Date de fin 8 Mars 2022

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 224 933,76

Contribution de l’UE

€ 224 933,76

Coordonné par

UNIVERSITY OF LEEDS
United Kingdom

Periodic Reporting for period 1 - PolyTEM (Understanding Crystal Polymorph Control in Confinement using In-situ TEM)

Période du rapport: 2020-03-09 au 2022-03-08

Résumé du contexte et des objectifs généraux du projet

Controlling the polymorph (crystal structure) of crystalline materials is of vital importance to both material science and the pharmaceutical industry. Many crystal polymorphs are difficult to access, however, as polymorph is determined by both kinetics and thermodynamics. Recently, it has been observed that precipitation of crystals in confinement often leads to the formation of unusual polymorphs. For example, CaCO3 forms purely as aragonite when it is precipitated in small nanopores. These observations suggest that confinement could offer a generic route to polymorph control. However, the fundamental mechanisms underlying this confinement effect are poorly understood. In this project, Dr. Yifei Xu uses in-situ transmission electron microscopy (TEM) to study how confinement effects give rise to polymorph control. CaCO3 forms the principal focus of the study, and a graphene pocket (GP) is used as the confinement system. We expect the study to not only advance our knowledge of crystal polymorphism, but also pave the way for rationally using confinement to control crystal polymorph in industry and lower down the cost of relevant products such as Ritonavir. By the end of this project, we have confirmed that GP can significantly control the polymorph of CaCO3. Using in-situ TEM in combination with other techniques, we have performed 3D high-resolution observation of the crystal nucleation processes in GP, and figured out the underlying mechanisms. Furthermore, we discovered that the GP can control the polymorph of several other crystals as well, indicating its potential for industrial applications.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

During the project we have performed in-situ cryoTEM and electron tomography (ET) study of the GP structure as well as the precipitation process of CaCO3 in the GPs. Furthermore, we have systematically studied the roles of the surface chemistry and morphology of GP using in-situ TEM in combination with a variety of other techniques such as X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM), and we have investigated whether GP can also affect the polymorph of other crystals. Below is a summary of the main results:

R1- CryoTEM and electron tomography (ET) visualisation of GP structure
R2- CryoTEM and ET visualisation of CaCO3 formation in GPs
R3- Determined the impact of GP on nucleation rate
R4- Determined the role of supersaturation
R5- Determined the role of GP morphlogy
R6- Determined the role of GP surface chemistry
R7- Determined how to prepare GPs with best performance
R8- Discovered that GP is also able to tune the polymorph of other crystals

A publication reporting our findings is now in preparation.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

Our results demonstrate the strong ability of GP in controlling the polymorph of many crystals, which originate from its confinement effect. The next step would be exploring whether such an ability could be applied for a large scale and more efficient synthesis of useful pharmaceutical products. We are discussing with several industrial companies about potential collaborations on this. Another interesting question would be whether pockets formed by other 2D materials such as MoS2, BN or clay can also control polymorph so effectively, which will also be investigated in our future researches and potentially can further lower down the cost of the method.

CryoET reconstruction slice showing an aragonite nucleus formed within the GP

SEM image showing the facilitated nucleation of aragonite around GPs