Solubility crystal structure disruption

Detailed studies on the pH-dependent solubility of L-PEI have shown that ca. 10% of protonated amines is required to disrupt the polymer crystal structure and to dissolve the polymer in water. This solubility behaviour also explains the incomplete alkaline hydrolysis of PAOx when converting it to L-PEI. Hence L-PEI is usually employed as a salt, invariably the hydrochloride salt, and the properties of other salts are largely unknown. L-PEI displays an overall pTsTg of 7.2-7.9, whereas B-PEI of 25 kDa displays a bulk pkTa of 8.4 with the individual pTsTg of the 1°, 2° and 3° amines being ca. 9, ca. 8 and 6-7, respectively. Hence at physiological pH of 7.4, approximately 55% of the amines in L-PEI will be protonated in comparison to 90% of the amines of B-PEI. 

In order to disrupt the crystal structure and improve solubility, longer pendent arms were placed in the 4-positions of the quinoline units. With an arm at least two phenylene units long, the crystal packing observed for 5 (x=2) could not be achieved, and a third phenyl... 

The interactions among solute molecules are a reflection of their chemical structure. The manifestations of this structural influence are the physical properties associated with their intermolecular binding. As examples, the melting point reflects the ease of crystal disruption to bring about a state change. The solubility is another phenomenon derived from the structural influences on the binding of solute molecules in a crystal. 

It is difficult to accurately predict aqueous solubility from chemical structure, because it involves disruption of the crystal lattice as well as solvation of the compound. Simple methods based on log P and melting temperature have been widely used [113, 114]. Recently, various prediction methods have been reported [115-125] that are able to predict aqueous solubility to within ca. 0.5 log units (roughly a factor of 3 in concentration). Although these predictors may not be precise or robust enough to select final compounds, they can be used as rough filters for narrowing the list of candidates. 

Unlike structured liquids, these unstructured, low-viscosity, clear liquids can be developed only if the onset of the formation of liquid crystals is hindered or they are broken up. This can be accomplished by two different methods by the addition of hydrotropes and solvents which can disrupt or prevent any liquid crystal formation as well as aid in solubilizing the other components in the formulation or by increasing the water solubility of the individual components. More than likely a combination of both these techniques is used to develop a stable liquid. The respective costs of these approaches ultimately determine their usage in the final formulation. Some of the methods used to formulate stable, single-phase, clear unstructured liquids are summarized below. 

Biological macromolecules such as polysaccharides, fibrous or membrane proteins characteristically adopt a unique secondary structure which may be related to a variety of physical or biological properties. Elucidation of the three-dimensional structure of these systems is not always straightforward, because, in many instances, they are insoluble in ordinary solvent systems, and crystallization for X-ray diffraction study is extremely difficult. A possible disruption of a particular secondary structure should also be anticipated, when they are solublized in a solvent or detergent. Therefore it is essential to clarify their secondary structures either in the solid, gel or membrane-bound state without any attempt at solubilization. 

Esters of 2-iodoxybenzoic acid (IBX-esters) 489 have been prepared by the hypochlorite oxidation of the readily available 2-iodobenzoate esters 488 (Scheme 2.139) and isolated in the form of stable microcrystalline solids [657,658], This procedure has been used for the synthesis of IBX-esters 489 derived from various types of alcohols, such as primary, secondary and tertiary alcohols, adamantanols, optically active menthols and borneol. Single-crystal X-ray data on products 489 revealed a pseudo-benziodoxole stmcture in which the intramolecular L--0 secondary bonds partially replace the intermolecular I - O secondary bonds, disrupting the polymeric structure characteristic of Phl02 and other previously reported iodylarenes [658], This stmctural feature substantially increases the solubility of these compounds in comparison to other iodine(V) reagents and affects their oxidizing reactivity. 

---