Experimental mechanochemical screening of cocrystals with linezolid (LIN) resulted in the formation of six new crystal phases, including three neat cocrystals and three cocrystal hydrates, in addition to seven previously described cocrystals. In an attempt to understand the factors governing the formation of these phases, different experimental conditions of the mechanochemical reactions (polymorphic forms of LIN and presence of different solvents to create liquid-assisted grinding conditions) were tested and the results were compared with the predictions from three commonly used virtual cocrystal screening tools: molecular complementarity, hydrogen bond propensity, and molecular electrostatic potential maps. It is shown that these three methods can be used to help understand a molecule’s preferences to form cocrystals with particular coformers. The influence of molecular conformation on the outcome of the predictions is also evaluated. A comparison between the prediction methods indicates that while considering a set of similar coformers, the approach based on molecular electrostatic potential maps seems to be more consistent with the experimental results than molecular complementarity and hydrogen bond propensity tools. Instead, these two latter approaches are recommended at the early stages of coformer selection. In addition, intermolecular energy contribution (lattice energy) to the total energy of crystal forms of coformers was found to be indicative of the feasibility of cocrystal formation in the case of coformers capable of forming similar supramolecular synthons.

Many species from the Pinaceae family have been recognized as a rich source of lignans, flavonoids, and other polyphenolics. The great common occurrence of conifers in Europe, as well as their use in the wood industry, makes both plant material and industrial waste material easily accessible and inexpensive. This is a promising prognosis for both discovery of new active compounds as well as for finding new applications for wood and its industry waste products. This study aimed to analyze and phytochemically profile 13 wood extracts of the Pinaceae family species, endemic or introduced in Polish flora, using the LC-DAD–ESI-MS/MS method and compare their respective metabolite profiles. Branch wood methanolic extracts were phytochemically profiled. Lignans, stilbenes, flavonoids, diterpenes, procyanidins, and other compounds were detected, with a considerable variety of chemical content among distinct species. Norway spruce (Picea abies (L.) H.Karst.) branch wood was the most abundant source of stilbenes, European larch (Larix decidua Mill.) mostly contained flavonoids, while silver fir (Abies alba Mill.) was rich in lignans. Furthermore, 10 lignans were isolated from the studied material. Our findings confirm that wood industry waste materials, such as conifer branches, can be a potent source of different phytochemicals, with the plant matrix being relatively simple, facilitating future isolation of target compounds.

In this Highlight the most important approaches in CSP to tackle molecular flexibility are characterized. Their successful use for drug-like molecules emphasizes the maturity of zeroth order CSP, while limitations indicate places for improvement.