## 1 Predictive Methods for Physicochemical Properties of Molecules
### Current Methods  
As mentioned in the introduction here we focus on the required accuracy and reliability of a predictive method, whereas a significant additional benefit would be the on the fly (instantaneous) prediction of a property, the latter being of particular interest for technologists carrying out (dynamical) process design. _Ab-initio quantum mechanical calculations_ are based on solving the Schrodinger equation in one way or the other and thus start from basic physical principles. They allow the calculation of a range of properties including heat of formation, free energy of formation, dipole moment and many more, without the necessity to have available any experimental data for parametrisation. Many other properties are not within reach, for example the melting point of a substance or the prediction of toxicity (unless, in the latter case, we would know the exact mechanism of action of what makes a molecule toxic at the molecular level). Furthermore, ab-initio methods and most certainly when the required accuracy needs to be approached, is computationally expensive and therefore inappropriate for rapid screening in for instance process design. A single quantum mechanical ab initio or Density Functional Theory (DFT) calculations take in the order of hours per molecule (on a single CPU). Calculating 'on the fly' would is not an option and, moreover, it generally requires expert knowledge to perform these calculations properly. Unfortunately and despite some reports in literature that appear optimistic, these methods have, generally speaking, not reached the accuracy and reliability level required [5]. The optimism in literature is often based on the fact that a specific class of related molecules is being treated with a specific method (e.g., alkanes or alcohols only) or so-called hybrid calculational schemes (technically speaking we refer to methods like G2, G4, etc.) which are in fact semi-empirical approaches as parameters were optimized in these schemes to obtain the best possible result for a certain, rather finite, set of test molecules. On the other hand, _ab-initio_ methods can be used to allow for the calculation of molecular descriptors that can be used in Quantitative Structure Activity Relationship (QSAR) approaches involving those molecular descriptors (see further below in this review). To obtain reasonable bond lengths and other geometrical information as well as for instance atomic chargesab initio methods can be used which are not very expensive. In this way ab initio calculations can make a most valuable contribution in conjunction with statistical QSAR methods involving molecular descriptors, as they can be applied to compound classes including organometallics. Many of the most prominent papers up till 2010 are quoted in the Reference [5]. A paper involving molecular simulations starting from molecular structures computed by quantum mechanics revealed predicted molecular liquid densities that are getting close to what is needed (\(<2\%\)) with the root-mean-squared deviations for halogenated compounds being the largest outlier (3.4%) [6]. As an alternative to the more rigorous but time-demanding ab initio calculations, for which one should also have the proper expertise, semi-empirical quantum mechanical methods such as the AM1 or PM6 methods can be very useful but have become somewhat forgotten despite good performance in areas like molecular entropy of organics [7], whereas we also refer to a more recent study involving semi-empirical quantum calculations review focusing on heat capacities and energies of organics [8].