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The Prelude of Green Syntheses of Drugs and Natural Products
Published in Ahindra Nag, Greener Synthesis of Organic Compounds, Drugs and Natural Products, 2022
Leonardo Xochicale-Santana, C. C. Vidyasagar, Blanca M. Muñoz-Flores, Víctor M. Jiménez Pérez
Cocrystals are defined by the Food and Drug Administration (FDA) as “crystalline materials composed of two or more different molecules, typically active pharmaceutical ingredient (API) and co-crystal formers (“coformers”), in the same crystal lattice.”34 There are two main methods for obtaining cocrystals: by solution and methods in solid states. The solution method consists of the combination of equimolar active pharmaceutical ingredient (API) and co-former in a solvent, and finally, when the solvent evaporates, the cocrystals are obtained. On the other hand, the solid methods consist of using mechanosynthesis by grinding in a mill or mortar.35 Cocrystals allow modifying the biopharmaceutical properties of an API such as solubility, dissociation speed, physicochemical stability, and hygroscopicity.36 Polymorphing is the ability of a compound to have more than one crystalline form. Some techniques for manipulating the crystalline form of APIs were previously mentioned; however, the newest technique is the formation of cocrystals, consisting of an API and one or more cocrystal forming agents. For the formation of cocrystals, it is important to consider some factors; among the most important ones are the functional groups of the API that allow molecular recognition by the cocrystallizing agent (co-former) through non-covalent interactions (heterosynthons and hydrogen bonding).37 Among the most common co-forming agents, we can find carbohydrates, amino acids, alcohols, amines, and carboxylic acids.21
Reduce Derivatives
Published in Aidé Sáenz-Galindo, Adali Oliva Castañeda-Facio, Raúl Rodríguez-Herrera, Green Chemistry and Applications, 2020
Revathi Kottappara, Shajesh Palantavida, Baiju Kizhakkekilikoodayil Vijayan
Non-covalent derivatives (NCD) possess properties that significantly differ from those of the parent molecules. NCDs can be of two types: cocrystals and eutectics. Simply, a cocrystal can be defined as an NCD formed by the combination of stoichiometric amounts of two or more molecules held together by non-covalent interactions. A eutectic is also a homogeneous material formed from two solids, but it can be identified as a minimum in a phase diagram (Ågerstrand et al., 2015). If the enthalpy change predominates the entropy loss in the process, the result will be a cocrystal, or will be an eutectic (Bouissou-Schurtz et al., 2014; Stoler and Warner, 2015). Non-covalent derivatization can result in significant variations in the properties including solubility, melting point, stability and optical parameters of the parent molecule. Compared to the conventional techniques of covalent derivatization using protecting groups salt derivatives etc., the NCDs is an effective alternative for bringing out the same kind of property modifications in a species while being less toxic, generates lesser amount of waste and thus more environmentally benign (Gee and Green, 1998; Anastas and Eghbali, 2010).
Introduction
Published in Jubaraj Bikash Baruah, Principles and Advances in Supramolecular Catalysis, 2019
Though the self-complementing properties of two hydrogen bond partners makes it possible to have strong hydrogen bonds, the intrinsic acidity or basicity plays a major role in hydrogen bond formation. When an acid and a base interact, they either form hydrogen-bonded cocrystal, supramolecular adduct or salt; in the last case, the base may abstract the proton, generating cation and leave aside other part as counter anion. In such situations, the pKa values of the acids predict the formation of solid adducts as cocrystal or salt. The latter is formed by protonation-deprotonation. Experiments that are generally carried out in solution provide high flexibility to have equilibrium for the exchange of protons between an acid and base. In such a condition, distinction between a cocrystal and salt may not be possible. There is an empirical way to predict salt and cocrystal formation. Salts are formed between an acid and base when ΔpKa (pKabase–pKaacid) is greater than 2. This relationship is not universal, as there are other contributions from the lattice to affect the validity of such a prediction. There are examples of salts forming further adducts with the acid or base partners through weak interactions. In the context of supramolecular catalysis, such interactions are very important in ionic liquids, surfactants, solid catalysts, nanocatalysts and acid-base catalysis. The complementing weak interactions other than hydrogen bonds guide the stability of many self-assemblies. For example, one may consider the interactions between a quinoline molecule with a carboxylic acid. There are three ways 1.11a–c to form hydrogen-bonded units by quinoline with a carboxylic acid (Figure 1.11) without forming the corresponding salt. One simple way is the discrete N─H⋯O interaction. Other ways to represent different hydrogen-bonded motifs include cyclic units of hydrogen-bonded structures having two hydrogen bond donors and two acceptors forming an eight-membered unit or formation of a hydrogen-bonded cyclic unit with two hydrogen bond donors and two hydrogen bond acceptors containing seven atoms. The other form of salt 1.11d is unlikely to form which is reflected in high energy of this form in theoretical calculation. The three units 1.11a–c are found in self-assemblies of quinoline interacting with carboxylic acids, depending on crystallization conditions and the other functional group attached on the carboxylic acid.
Energetic competition in the complexation affinity of paracetamol with water and oxalic acid
Published in Molecular Physics, 2023
Amanda Studinger, Loredana Valenzano-Slough
Intermolecular interactions such as hydrogen bonds and van der Waals forces are the driving forces for many practical applications of active pharmaceutical ingredients (APIs). In the design and manufacturing process, it is beneficial to produce APIs as cocrystals with another molecule (cocrystal conformers) to create stable crystalline structures that have the desired physicochemical properties [1]. API cocrystals are also designed to maximise the pharmacokinetic properties of the final product such as absorption, distribution, metabolism, and excretion. In this regard, hydrogen bond nets and interlayered van der Waals forces play a major role in how the API crystals are formed during manufacturing, and how easily they are dried, pelletised or encapsulated, transported and stored. In addition to influencing the pharmacokinetic properties in vivo, the final crystal structure’s unique intermolecular interactions and how they are influenced by their surrounding environment can influence the pharmacodynamics of a drug regarding how it binds to targeted receptors. In addition, after the drug is used or metabolised, or when excess drugs enter waste streams, the same intermolecular interactions act again in a wide array of chemical environments in the water and soil with these processes dictating how the APIs are transported and/or stored in the environment [2].