Introductory lecture: Mechanochemistry, a versatile synthesis strategy for new materials.

William Jones,Mark D. Eddleston

doi:10.1039/c4fd00162a

William Jones, Mark D. Eddleston

Open Access

https://doi.org/10.1039/c4fd00162a

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Journal: Faraday discussions	Publication Date: Jan 1, 2014
Citations: 97	License type: cc-by

Affiliation: University of Cambridge

Abstract

Mechanochemistry deals with reactions induced by the input of mechanical energy - for example by impacts within a vibratory ball mill. The technique has a long history with significant contributions from Ostwald, Carey Lea and, notably, Faraday. Mechanochemistry has subsequently seen application in a variety of areas of materials science including mechanical alloying in metallurgy, the synthesis of complex organic molecules and, more recently, the discovery and development of new solid forms of active pharmaceutical ingredients. This paper overviews the broad areas of application of mechanochemistry, some key features which make it a particularly attractive approach to materials synthesis and some mechanistic aspects highlighted within the literature. A significant part, however, will focus on recent applications in the area of pharmaceuticals and its important role in exploring the rich variety of solid forms available for small, drug-like, molecules.

Highlights

Mechanochemistry is a long-established method for the synthesis of solids and molecules
In the case of pharmaceutical solids, recent work using atomic force microscopy (AFM), terahertz spectroscopy and transmission electron microscopy (TEM) suggests that these techniques will be important for characterising mechanically treated samples and understanding changes which occur during such processing
In the case of aspirin and dicalcium phosphate, when the excipient was attached to the tip of the AFM cantilever and different pressures and contact times under various humidity conditions there was evidence for enhanced reactivity induced by surface contact with excipient.[91]

Summary

Introduction

Mechanochemistry is a long-established method for the synthesis of solids and molecules. As we will describe later, the amount of energy which can be imparted to a system under mechanical activation can be signi cant – certainly sufficient to break chemical bonds6 – but can be reduced when working with systems such as so molecular crystals in order to minimise chemical activation while still enabling processes such as the conversion of a crystalline solid to an amorphous product,[11] or the readjustment of molecules within a lattice Such readjustments may lead to the introduction of lattice imperfections,[12] to polymorphic transformations[13] or to the intimate mixing of two separate crystalline molecular solids to create a crystalline multicomponent product indistinct from that which would be obtained by a conventional solution crystallisation.[14] advantageous in mechanochemical transformations is the avoidance of the need for large volumes of solvent (as required, for example, in the recrystallization of poorly soluble molecules), and a strong “Green Chemistry” aspect to mechanochemistry is recognised.[15,16] In terms of commercial interest, the review by James et al describes a search of patent applications for the terms “mechanochemical” and “mechanochemistry” which revealed a signi cant increase in usage in the patent literature from 1980 onwards.[6]

Areas of application and development

Pharmaceutical materials

Findings

Concluding remarks