Reactivity and properties of molecules change under the influence of mechanical forces.
About the project
Mechanical influence is important in chemistry. Trivial examples include grinding of metal mixtures for the formation of amalgams and stirring of reaction mixtures in organic chemistry. Besides being useful for obtaining homogenous mixtures, application of an external force or pressure to a chemical system may result in interesting alteration of molecular properties and reactivity, and sometimes dramatic changes are observed. For example, hydrogen becomes a metal above 100 GPa, induction of electronic overlap is observed between noble gas atoms confined in small cavities, improved yield in synthesis is obtained using ultrasound (sonochemistry), and the phenomenon of piezoelectricity results from the response of an external force to specific solid materials. Reversely, detonation of energetic substances leads to propagation of a shock wave, while certain proteins act on their environment by exerting force, as in muscle action.
Recently, the effect of mechanical strain has been studied experimentally by using atomic-force microscope (AFM). By anchoring a polymer molecule at one end to the base of the AFM and at the other end to the cantilever tip, while increasing the base–tip separation in a controlled fashion, it becomes possible to monitor continuously the force acting on the molecule. From the recorded force-extension profile, it is possible to follow the stretching of the molecule all the way from its initial equilibrium state via intermediate states up to a transition state, where the mechanically weakest covalent bond of the backbone breaks. In other situations stretching a molecule may bring it closer to the transition state of a reaction of that molecule. We may term this force-enhanced reactivity. Both these processes have been investigated experimentally using AFM, but are of yet incompletely understood.
Quantum chemical methods
Within the CTCC we have made efforts in modelling molecule stretching and activation using quantum chemical methods, partly in collaboration with Julio Fernandez of Columbia University, who is a pioneer in AFM experiments with biological molecules. The key parameters during molecular stretching is the location of the bond-breaking point, the bond-rupture force and the kinetics, i.e. the dissociation probability as a function of the temperature and applied force. In one study Iozzi et al. investigated the performance of some commonly used quantum-chemical methods in accurately and reliably describing these parameters for a set of small molecules. By applying coupled-cluster CCSD(T) theory in an extended basis set as benchmark, all methods tested provide a good qualitative description of the physical process, although the quantitative agreement varies considerably. In addition, it was demonstrated that the essence of mechanical bond breaking is captured by single-reference-based methods. Estimates of the dissociation probability shows that it depends strongly on the description of the potential-energy curve.
The disulfide bond
In a second study the mechanochemistry of the disulfide bond was characterized. The disulfide bond is important in biology and our study included a model of the I27 domain in the titin protein, a muscle protein. Upon stretching the diradical character of the disulfide bridge increases while the energy difference between the singlet ground state and low-lying triplet state decreases. Moreover, an external force in the range 0.1–0.4 nN, promotes the disulfide reduction. The numerical description of the interplay between force and reaction mechanism is in good qualitative agreement with experimental observations.
Our efforts are partly in collaboration with Julio Fernandez of Columbia University, who is a pioneer in AFM experiments with biological molecules.