Cocrystallization properties

Etter, M. C., Z. Urbanczyk-Lipowska, M. Zia-Ebrahimi, and T. W. Pananto. 1990. Hydrogen Bond Directed Cocrystallization and Molecular Recognition Properties of Diaryl Ureas. J. Am Chem. Soc. 112, 8415. 

Fe(Cp-C0NHCH2S03)2] anion have been identified (TTF)2[Fe(Cp-CONHCH2 S03)2] and the solvated (TTF)2[Fe(Cp-C0NHCH2S03)2]-2CH30H. Both crystal structures contain face-to-face dimers, with the main structural differences probably attributed to hydrogen bonding to the cocrystallized methanol. No physical properties of these salts have yet been published. 

The cholesterol-lowering properties of dietary plant sterols have been known for decades (Best et al., 1954 Peterson, 1951 Poliak, 1953), due specifically to reductions in cholesterol absorption. Inverse correlations between plant sterol intake and cholesterol absorption have been reported in animals (Carr et al., 2002 Ntanios and Jones, 1999) and humans (Ellegard et al., 2000). The exact mechanism by which plant sterols inhibit cholesterol absorption is unclear, and several mechanisms of action have been proposed, including (1) competition with cholesterol for solubilization in micelles within the intestinal lumen, (2) cocrystallization with cholesterol to form insoluble crystals, (3) interaction with digestive enzymes, and (4) regulation of intestinal transporters of cholesterol. 

C.C. Sun, H. Hou, Improving mechanical properties of caffeine and methyl gallate crystals by cocrystallization, Cryst. Growth Des. 8 (2008) 1575-1579. 

A remarkable property of the Re-H bonds in polyhydrides is their ability to establish a new kind of hydrogen bond, M-H- HX (X = O, N, C), called protonic-hydridic or dUiydrogen bonds. Initially found in intramolecular systems, they can also be formed intermolecularly as established by neutron diffraction of the adduct ReH5(PPh3)2-C8H6 NHCeHe formed in the cocrystallization of the hydride with indole in benzene. ... 

Etter, M. C., Urbanczyk-Lipkowska, Z., Zia-Ebrahimi, M. and Panunto, T. W. (1990ft). Hydrogen bond-directed cocrystallization and molecular recognition properties of diarylureas. / Am. Chem. Soc., 112, 8415-26. [55, 56,77]... 

As scientists become more aware of a substantial expansion in the scope of solid-state structural variations that can be obtained through the cocrystallization of several molecules in a single lattice structure, studies of the mixed molecular crystal systems known as cocrystals have mushroomed [1-3]. Along these lines, workers have researched the assembly of supramolecular symthons and crystal engineering in ever-increasing efforts to produce materials having new and useful properties [4],... 

The mixed-crystal system formed by indomethacin and saccharin (l,2-benzisothiazol-3(2H)-one-l,1-dioxide) has been used to evaluate the feasibility of using supercritical fluids as media for the design and preparation of new cocrystals [44]. In this work, the relative merits of supercritical fluid processes (i.e., cocrystallization with a supercritical solvent, supercritical fluid as anti-solvent, and the atomization and anti-solvent technique) were evaluated, as well as the influence of processing parameters on product formation and particle properties of the yields. It was reported that while the anti-solvent and atomization procedures yielded pure cocrystal products, only partial to no cocrystal formation took place when using the crystallization process. 

It was a long-standing puzzle in the 1930s that intense color was seen in crystals and solutions of weak stoichiometric (1 1) complexes (benzene (1) with iodine (I2), or naphthalene (2) with trinitrobenzene (TNB, 7)) and other similar systems. This intense color formed when the components are mixed in solution, and cocrystallized as stoichiometric solid-state complexes. These solutions and crystals showed, almost unchanged, the full optical absorption spectrum of the neutral components, plus an extra broad, intense absorption band with little or no vibrational structure one seemed to get something (color) for nothing (no change in other properties). 

We will first describe some of the theoretical aspects for cocrystal design, followed by a summary of the pharmaceutical properties of cocrystals, including their solubility dependence on cocrystal component concentration and in some cases on solution pH. Processes for cocrystal formation will be presented by considering the factors that control cocrystallization kinetics and mechanisms in solution and in solid-state mediated processes. This article will be useful to the reader who wishes to anticipate cocrystal formation during pharmaceutical processes and storage and to those who wish to proactively discover new phases. 

Cocrystals are becoming increasingly important as a means of controlling the properties of pharmaceutical solids by designing multiple component molecular networks that introduce the desired functionality. Because cocrystal design is based on supramolecular synthesis, it provides a powerful approach for the proactive discovery of novel pharmaceutical solid phases. Application of the fundamental concepts presented here on cocrystallization processes is essential for the pharmaceutical scientist to anticipate the formation of cocrystals during pharmaceutical processes and storage, as well as to develop reliable methods for cocrystal discovery and production. 

The divalent ions of the heavy actinoids Md and No facilitate separation of the elements, although this property has not yet been extensively exploited. Cocrystallization (Fm with SmCl2) and chromatographic extraction (Md and No with HDEHP) utilize the divalent character of these elements . 

The main criterion for isosterism is that two isosteric molecules must present similar, if not identical, volumes, and shapes. Ideally, isosteric compounds should be isomorphic and able to cocrystallize. Among the other physical properties that isosteric compounds usually share one can cite boiling point, density, viscosity, and thermal conductivity. However, certain properties must be different dipolar moments, polarity, polarization, size, and shape (e.g. in comparing E and OH , the size and the shape of H cannot be totally neglected). After all, the external orbital may be hybridized differently. 

An involvement of different kinds of comonomer component units in the crystalline lattice of the main component unit of a copolymer should influence the bulk properties of a solid-state copolymer. As found for P(3HB-co-3HV) copolymers, the comonomer composition in the crystalline phase is not always the same as that in the noncrystalline phase. Hence, it is of great interest to investigate theoretically a comonomer composition in a crystalline phase. The cocrystallization ability of P(3HB-co-3HV) copolymers has been investigated from two different viewpoints, i.e., thermodynamically [61] and in terms of molecular mechanics [62]. 

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