## 1 Predictive Methods for Physicochemical Properties of Molecules
### Current Methods
There current use seems limited, despite some very useful specific applications in combination with the calculations being very fast, as the performance area is limited (the classes of molecules and properties for which proper parametrization was accomplished in the past) or simply insufficiently accurate (non-organics),  
In the _QSPR (Quantitative Structure Property Relationships)_ approach, in which so-called molecular descriptors are involved that characterise the molecule, descriptors are linked with the physicochemical property of interest by establishing a relation  
\[\text{Physicochemical property of interest}=f\text{ (molecular descriptors)} \tag{1}\]  
Molecular descriptors are parameters that describe characteristics of the molecule and vary from geometrical parameters such as bond lengths and bond angles to atomic charges, atom-atom connectivity, molecular volume, cone angles, HOMO and LUMO energies and so on. Formally, a definition of such descriptors was given by [PERSON] and [PERSON] [9]. Descriptors can be evaluated by well-established procedures and available programs. One methodology largely uses quickly calculable parameters including those based on geometry and connectivity, (partial) molar volumes, components of the dipole and quadruple moment vectors and many more. In fact, the data presented in Figure 4 were based on such an approach (homogeneous catalysts). The descriptors can be computed using software programs such as DRAGON ([[http://www.molecular](http://www.molecular)]([http://www.molecular](http://www.molecular)) descriptors.eu/resources/resources.htm) or CODESSA ([[http://codesa.weebly.com/software.html](http://codesa.weebly.com/software.html)]([http://codesa.weebly.com/software.html](http://codesa.weebly.com/software.html))), the MS.QSAR module of Accelrys Inc. and many more, all easy to connect to on the Internet, several of these are freeware. For a useful further reference on molecular descriptors see Reference [10]: \"The great descriptor melting pot: mixing descriptors for the common good of QSAR methods.\" An excellent introduction describing various approaches and their advantages and disadvantages was presented by [PERSON] et al. [11]. The other way to obtain (additional) molecular descriptors is to use ab initio quantum mechanical calculations to compute the geometry and electronic structured of a molecule and from that derive a large set of molecular descriptors [12]. Both approaches can be used individually or combined. Next to using ab-initio methods, the much faster semi-empirical quantum mechanics methods can be used to generate and evaluate molecular descriptors. Next, a mathematical relation (viz. Equation (1)) is established between the descriptors and each property of interest. This can be accomplished by statistical methods optimizing the parameters to be fitted in the model. In many cases a PCA (principal component analysis) is performed first so only the most relevant (statistical correlation) descriptors are retained. As the total number of descriptors easily runs into many hundreds, this PCA reduces the risk of overfitting (many fitting parameters many lead to very different models for the same property, a risk that can only be overcome by having a much larger set of property data compared to the number of molecular descriptors). This class of methods is generally applicable, for any type of molecule. When a property is required for a new molecule, the descriptor values for that new molecule are calculated and substituted into the model, which then provides the predicted value for the property of relevance. This methodology has been applied to a very wide range of properties, from which we can only name a few. Surfactant cloud points [13], pKa [14], normal boiling points [15] and another one in which the impressive number of 17768 pure chemical compounds were considered and which includes an overview of previous models [16], octanol-water partition coefficients [17] and homogeneous catalysis [18].