Prediction of Mefenamic Acid Crystal Shape by Random Forest Classification.

OBJECTIVE: Particle shape can have a significant impact on the bulk properties of materials. This study describes the development and application of machine-learning models to predict the crystal shape of mefenamic acid recrystallized from organic solvents. METHODS: Crystals were grown in 30 different solvents to establish a dataset comprising solvent molecular descriptors, process conditions and crystal shape. Random forest classification models were trained on this data and assessed for prediction accuracy. RESULTS: The highest prediction accuracy of crystal shape was 93.5% assessed by fourfold cross-validation. When solvents were sequentially excluded from the training data, 32 out of 84 models predicted the shape of mefenamic acid crystals for the excluded solvent with 100% accuracy and a further 21 models had prediction accuracies from 50-100%. Reducing the feature set to only solvent physical property descriptors and supersaturations resulted in higher overall prediction accuracies than the models trained using all available or another selected subset of molecular descriptors. For the 8 solvents on which the models performed poorly (< 50% accuracy), further characterisation of crystals grown in these solvents resulted in the discovery of a new mefenamic acid solvate whereas all other crystals were the previously known form I. CONCLUSIONS: Random forest classification models using solvent physical property descriptors can reliably predict crystal morphologies for mefenamic acid crystals grown in 20 out of the 28 solvents included in this work. Poor prediction accuracies for the remaining 8 solvents indicate that further factors will be required in the feature set to provide a more generalized predictive morphology model.

Anthracene as a Launchpad for a Phosphinidene Sulfide and for Generation of a Phosphorus-Sulfur Material Having the Composition P2S, a Vulcanized Red Phosphorus That Is Yellow.

Thermolysis of a pair of dibenzo-7-phosphanorbornadiene compounds is shown to lead to differing behaviors: phosphinidene sulfide release and formation of amorphous P2S. These compounds, tBuP(S)A (1, A = C14H10 or anthracene; 59% isol. yield) and HP(S)A (2; 63%), are available through thionation of tBuPA and the new secondary phosphine HPA (5), prepared from Me2NPA and DIBAL-H in 50% yield. Phosphinidene sulfide [ tBuP═S] transfer is shown to proceed efficiently from 1 to 2,3-dimethyl-1,3-butadiene to form Diels-Alder product 3 with a zero-order dependence on diene. Platinum complex (Ph3P)2Pt(η2- tBuPS) (4, 47%) is also accessed from 1 and structurally characterized. In contrast, heating parent species 2 (3 h, 135 °C) under vacuum instead produces an insoluble, nonvolatile yellow residual material 6 of composition P2S that displays semiconductor properties with an optical band gap of 2.4 eV. Material 6 obtained in this manner from molecular precursor 2 is in a poorly characterized portion of the phosphorus-sulfur phase diagram and has therefore been subjected to a range of spectroscopic techniques to gain structural insight. X-ray spectroscopic and diffraction techniques, including Raman, XANES, EXAFS, and PDF, reveal 6 to have similarities with related compounds including P4S3, Hittorf's violet phosphorus. Various possible structures have been explored as well using quantum chemical calculations under the constraint that each phosphorus atom is trivalent with no terminal sulfide groups, and each sulfur atom is divalent. The structural conclusions are supported by data from phosphorus-31 magic angle spinning (MAS) solid state NMR spectroscopy, bolstering the structural comparisons to other phosphorus-sulfur systems while excluding the formulation of P2S as a simple mixture of P4S3 and phosphorus.

Probing covalency in halogen bonds through donor K-edge X-ray absorption spectroscopy: polyhalides as coordination complexes.

The properties of halogen bonds (XBs) in solid-state I2X- and I4X- materials (where X = Cl, Br) are explored using donor K-edge X-ray absorption spectroscopy (XAS) to experimentally determine the degree of charge transfer in such XB interactions. The degree of covalency in these bonds is substantial, even in cases where significantly weaker secondary interactions are observed. These data, in concert with previous work in this area, suggests that certain halogen bonds have covalent contributions to bonding that are similar to, and even exceed, those observed in transition metal coordinate bonds. For this reason, we suggest that XB interactions of this type be denoted in a similar way to coordination bonds (X → Y) as opposed to using a representation that is the same as for significantly less covalent hydrogen bonds (XY).

Evidence for halogen bond covalency in acyclic and interlocked halogen-bonding receptor anion recognition.

The synthesis and anion binding properties of novel halogen-bonding (XB) bis-iodotriazole-pyridinium-containing acyclic and [2]catenane anion host systems are described. The XB acyclic receptor displays selectivity for acetate over halides with enhanced anion recognition properties compared to the analogous hydrogen-bonding (HB) acyclic receptor. A reversal in halide selectivity is observed in the XB [2]catenane, in comparison to the acyclic XB receptor, due to the interlocked host's unique three-dimensional binding cavity, and no binding is observed for oxoanions. Notable halide anion association constant values determined for the [2]catenane in competitive organic-aqueous solvent mixtures demonstrate considerable enhancement of anion recognition as compared to the HB catenane analogue. X-ray crystallographic analysis of a series of halide catenane complexes reveal strong XB interactions in the solid state. These interactions were studied using Cl and Br K-edge X-ray Absorption Spectroscopy (XAS) indicating intense pre-edge features characteristic of charge transfer from the halide to its bonding partner (σ(AX←X(-))(*) ← X1s), and providing a direct measure of the degree of covalency in the halogen bond(s). The data reveal that the degree of covalency is similar to that which is observed in transition metal coordinate covalent bonds. These results are supported by DFT results, which correlate well with the experimental data.

Demonstration of a standard dilution technique for standard addition calibration.

A standard dilution approach to sequential (S-SAC) and conventional (C-SAC) standard addition calibration is introduced and described theoretically. The two calibration methods have then been demonstrated experimentally for chloride measurement in seawater samples. S-SAC showed superior results for such a sample as a function of the steeper extrapolation resulting from the calibration process. The conflicting effects on S-SAC of extrapolation precision and sensitivity to intercept correction have been discussed and recommendations concerning the optimum ratio of target analyte concentration in the calibration standard to that in the unknown sample for the use of this technique have been made.