Elucidating chemical reactivity in complex molecular assemblies of a few hundred atoms is, despite the remarkable progress in quantum chemistry, still a major challenge. Black-box search methods to find intermediates and transitionstate structures might fail in such situations because of the high-dimensionality of the potential energy surface. Here, we propose the concept of interactive chemical reactivity exploration to effectively introduce the chemist's intuition into the search process. We employ a haptic pointer device with force-feedback to allow the operator the direct manipulation of structures in three dimensions along with simultaneous perception of the quantum mechanical response upon structure modification as forces. We elaborate on the details of how such an interactive exploration should proceed and which technical difficulties need to be overcome. All reactivity-exploration concepts developed for this purpose have been implemented in the Samson programming environment.

We present the software package MOVIPAC for calculations of vibrational spectra, namely infrared, Raman, and Raman Optical Activity (ROA) spectra, in a massively parallelized fashion. MOVIPAC unites the latest versions of the programs SNF and AKIRA alongside with a range of helpful add-ons to analyze and interpret the data obtained in the calculations. With its efficient parallelization and meta-program design, MOVIPAC focuses in particular on the calculation of vibrational spectra of very large molecules containing on the order of a hundred atoms. For this purpose, it also offers different subsystem approaches such as Mode-and Intensity-Tracking to selectively calculate specific features of the full spectrum. Furthermore, an approximation to the entire spectrum can be obtained using the Cartesian Tensor Transfer Method. We illustrate these capabilities using the example of a large p-helix consisting of 20 (S)-alanine residues. In particular, we investigate the ROA spectrum of this structure and compare it to the spectra of aand 3 10 -helical analogs.

Significant progress in the development of efficient and fast algorithms for quantum chemical calculations has been made in the past two decades. The main focus has always been the desire to be able to treat ever larger molecules or molecular assemblies-especially linear and sublinear scaling techniques are devoted to the accomplishment of this goal. However, as many chemical reactions are rather local, they usually involve only a limited number of atoms so that models of about 200 (or even less) atoms embedded in a suitable environment are sufficient to study their mechanisms. Thus, the system size does not need to be enlarged, but remains constant for reactions of this type that can be described by less than 200 atoms. The question then arises how fast one can obtain the quantum chemical results. This question is not directly answered by linear-scaling techniques. In fact, ideas such as haptic quantum chemistry (HQC) or interactive quantum chemistry require an immediate provision of quantum chemical information which demands the calculation of data in ' 'real time.' ' In this perspective, we aim at a definition of real-time quantum chemistry, explore its realm and eventually discuss applications in the field of HQC. For the latter, we elaborate whether a direct approach is possible by virtue of real-time quantum chemistry.

Chemical reactivity of a set of reactants is determined by its potential (electronic) energy (hyper)surface. The high dimensionality of this surface renders it difficult to efficiently explore reactivity in a large reactive system. Exhaustive sampling techniques and search algorithms are not straightforward to employ as it is not clear which explored path will eventually produce the minimum energy path of a reaction passing through a transition structure. Here, the chemist's intuition would be of invaluable help, but it cannot be easily exploited because (1) no intuitive and direct tool for the scientist to manipulate molecular structures is currently available and because (2) quantum chemical calculations are inherently expensive in terms of computational effort. In this work, we elaborate on how the chemist can be reintroduced into the exploratory process within a virtual environment that provides immediate feedback and intuitive tools to manipulate a reactive system. We work out in detail how this immersion should take place. We provide an analysis of modern semi-empirical methods which already today are candidates for the interactive study of chemical reactivity. Implications of manual structure manipulations for their physical meaning and chemical relevance are carefully analysed in order to provide sound theoretical foundations for the interpretation of the interactive reactivity exploration.