Polymorphs solvates and co-crystals of molecular materials

The scope of my research project is to produce and characterize new crystalline forms of organic compounds, focusing the attention on co-crystals and then transferring these notions on APIs to produce co-crystals of potential interest in the pharmaceutical field. In the first part of this work co-crystallization experiments were performed using as building blocks the family of aliphatic dicarboxylic acids HOOC-(CH2)n-COOH, with n= 2-8. This class of compounds has always been an object of study because it is characterized by an interesting phenomenon of alternation of melting points: the acids with an even number of carbon atoms show a melting point higher than those with an odd one. The acids were co-crystallized with four dipyridyl molecules (formed by two pyridine rings with a different number of bridging carbon atoms) through the formation of intermolecular interactions N•••(H)O. The bases used were: 4,4’-bipyridine (BPY), 1,2-bis(4-pyridyl)ethane (BPA), 1,2-(di-4-pyridyl)ethylene (BPE) and 1,2-bis(4-pyridyl)propane (BPP). The co-crystals obtained by solution synthesis were characterized by different solid-state techniques to determine the structure and to see how the melting points in co-crystals change. In the second part of this study we tried to obtain new crystal forms of compounds of pharmaceutical interest. The APIs studied are: O-desmethylvenlafaxine, Lidocaine, Nalidixic Acid and Sulfadiazine. Each API was subjected to Polymorph Screening and Salt/Co-crystal Screening experiments to identify new crystal forms characterized by different properties. In a typical Salt/Co-crystal Screening the sample was made to react with a co-former (solid or liquid) through different methods: crystallization by solution, grinding, kneading and solid-gas reactions. The new crystal forms obtained were characterized by different solid state techniques (X-ray single crystal diffraction, X-ray powder diffraction, Differential Scanning Calorimetry, Thermogravimetric Analysis, Evolved gas analysis, FT-IR – ATR, Solid State N.M.R).

Models and algorithms for real-world optimization problems

This thesis deals with efficient solution of optimization problems of practical interest. The first part of the thesis deals with bin packing problems. The bin packing problem (BPP) is one of the oldest and most fundamental combinatorial optimiza- tion problems. The bin packing problem and its generalizations arise often in real-world ap- plications, from manufacturing industry, logistics and transportation of goods, and scheduling. After an introductory chapter, I will present two applications of two of the most natural extensions of the bin packing: Chapter 2 will be dedicated to an application of bin packing in two dimension to a problem of scheduling a set of computational tasks on a computer cluster, while Chapter 3 deals with the generalization of BPP in three dimensions that arise frequently in logistic and transportation, often com- plemented with additional constraints on the placement of items and characteristics of the solution, like, for example, guarantees on the stability of the items, to avoid potential damage to the transported goods, on the distribution of the total weight of the bins, and on compatibility with loading and unloading operations. The second part of the thesis, and in particular Chapter 4 considers the Trans- mission Expansion Problem (TEP), where an electrical transmission grid must be expanded so as to satisfy future energy demand at the minimum cost, while main- taining some guarantees of robustness to potential line failures. These problems are gaining importance in a world where a shift towards renewable energy can impose a significant geographical reallocation of generation capacities, resulting in the ne- cessity of expanding current power transmission grids.