Solubility and Aggregation

It is difficult to predict the effect of surface functionalization on the optical properties of nanoparticles in general. Surface ligands have only minor influence on the spectroscopic properties of nanoparticles, the properties of which are primarily dominated by the crystal field of the host lattice (e.g., rare-earth doped nanocrystals) or by plasmon resonance (e.g., gold nanoparticles). In the case of QDs, the fluorescence quantum yield and decay behavior respond to surface functionalization and bioconjugation, whereas the spectral position and shape of the absorption and emission are barely affected. 

Why is it necessary to ask this question. At what time during the development of a compound should the question be asked. How correct does the answer need to be Who is best able to answer the question There are not necessarily simple or definitive answers to these questions. 

Hit and Lead Profiling. Edited by Bernard Faller and Laszlo Urban Copyright 2009 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-32331-9 

There is no specific person who can best answer the question concerning the solubility. At first a more qualitative answer might be obtained from the discovery chemist who needed to dissolve the compound in the different solvents used in the synthesis and purification of the compound. Later it should be determined by someone who is familiar with the nuances of measuring the solubility and those factors which can influence the final result. 

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It is well known that many compounds are able to change their physical form whilst suspended in solution. For example, a compound of interest may change from one polymorphic form to another, while different crystalline aggregations of the same compound can have different solubility profiles. Impurities can mask the true solubility, and aggregation in solution can also change the thermodynamic equilibrium. Finally, errors which have been published in the literature data may in fact magnify from publication to publication. 

When attempting to use NMR to measure a dissociation constant, the basic experiment will be to vary the ligand concentration in the presence of a fixed concentration of protein. (The converse experiment, varying the protein concentration, may sometimes be carried out, but is generally less satisfactory because of problems with protein solubility and aggregation.) What one sees in this experiment will depend critically on the rate of... 

It has been our approach to protein structure determination by x-ray crystallography that it is imperative to begin with well-characterized and well-behaved protein. In particular, it is important that the protein be reasonably soluble and monodisperse in solution. Unfortunately, as discussed above, recombinant HIV-1 integrase satisfies neither of these conditions. One approach we and others have taken to circumvent these problems has been to examine truncated versions of HIV-1 integrase to determine if removal of amino acids from either terminus or both affects solubility and aggregation properties. 

Ridder KB, Davies-Cutting CJ, and Kellaway IW. Surfactant solubility and aggregate orientation in hydrofluoroalkanes. Int J Pharm 2005 295 57-65. 

It has become increasingly clear that PTM can also occur in Archaea. Archaea express proteins that enable them to strive in harsh habitats. Archaeal proteins are able to remain properly folded and functional under extremely harsh conditions such as high salinity and temperature, and other adverse physical conditions that would normally cause protein denaturation, loss of solubility, and aggregation [31]. 

In the anhydrous microencapsulation, protein and excipients were suspended/dissolved in PLA/acetonitrile solution and then added to cottonseed oil to form an o/o emulsion with Span 85 as an emulsifier. Petroleum ether was then added to extract the acetonitrile and the microspheres were hardened. The microspheres were then recovered by filtration and dried under vacuum. As shown in Table 5 and Fig. 5, without the pore-forming PEG, only 36% BSA was released from PLA microspheres in 1-month of incubation with a total recovery (released-fall soluble and aggregated residue in polymer after release) of 76%. Blending in 30% of 35 kDa PEG with the PLA eliminated the BSA aggregation in polymer completely, with 82% of encapsulated BSA released in 1 month. The improved BSA stability in PLA/PEG microspheres could be attributed to a less acidic and more hydrophilic microenvironment in the polymer. As seen in Fig. 6, unlike PLGA 50/50, which caused a dramatic pH drop in the release medium after a 4-week incubation (41), a relatively neutral pH was retained in the release medium for both PLA and PLA/PEG microspheres. A slightly lower pH in the release medium incubated with PLA/PEG microspheres relative to that in PLA was also... 

Protein concentrations in solution are often limited by solubility and aggregation (and, of course, protein availability) to a maximum of 0.5-5 mM. Today most NMR structural studies are performed at 1-2 mM protein concentrations, although it can be expected that new technologies leading to increased sensitivity in NMR experiments (increased field strength, improved probe design, cryo-probes etc.) will lower the concentration requirements to the 100-mM range within the next few years. 

The effect of temperature and solvent on solubility and aggregation is discussed in references (17) and (18). 

Elshereef, R. Budman, H. Moresoli, C. Legge, R.L. Fluorescence spectroscopy as a tool for monitoring solubility and aggregation behaviour of /J-lactoglobulin after heat treatment. Biotechnology and Bioengineering, 2006, 95(5), 863-874. 

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