Self-Association of Nicotinamide in Aqueous Solution: Light-Scattering and Vapor Pressure Osmometry Studies

Abstract

Nicotinamide is a hydrotropic agent that has been reported to self-associate in aqueous solution. The objective of this study is to characterize the self-association of nicotinamide with regard to the extent of self-association as well as association constants using light-scattering and vapor pressure osmometry. Both methods allow calculation of association constants; however, while light-scattering measurements depend on the size of particles in solution, vapor pressure osmometry depends on the number of particles in solution. Using light-scattering, nicotinamide was found to associate primarily as dimers and trimers. Higher order aggregates can be characterized by an average aggregation number of 4.37. The association constants were 9.99 L/mol and 13.1 L/mol for dimerization and trimerization, respectively. From vapor pressure osmometry data were calculated a dimerization constant of 0.203 L/mol and a trimerization constant of 14.1 L/mol. In comparison, the trimerization constants are in good agreement, while the dimerization constants differ by an order of magnitude. Since light-scattering measurements are less reliable for small molecules like nicotinamide at low concentrations, it is felt that the dimerization constant calculated from vapor pressure osmometry is the more accurate.

Reparametrization of Protein Force Field Nonbonded Interactions Guided by Osmotic Coefficient Measurements from Molecular Dynamics Simulations

“…66 For the remaining molecules, all of which are alcohols (methanol, n-butanol and t-butanol), osmotic coefficients were instead obtained from freezing point depression experiments. 64 This technique yields an osmotic coefficient at the freezing point (i.e.…”

Interaction between Surface Active Drug (FK906:Rennin Inhibitor) and Cyclodextrins in Aqueous Solution

“…Although the aggregation number of FK906 molecules was much smaller than that of a reported drug substance such as a leukotriene D 4 receptor antagonist which aggregates more than 16000 molecules, 10 similar results to those from FK906 have been reported for some antibiotics 11 and nicotinamide. 12 2. 1 H-Nuclear Magnetic Resonance StudysFigure 2 shows the 1 H NMR spectrum of FK906 in D 2 O.…”

Molecular Dynamics Simulations of Hydrotropic Solubilization and Self-Aggregation of Nicotinamide

“…1 A term first coined at the beginning of 20th century, 2 hydrotropy has been found to occur to a diverse collection of chemical structures. [3][4][5][6][7] The nature and mechanism of this phenomenon have raised great interests, and to that end a variety of experimental techniques have been invoked, which include UV/Vis and fluorescence spectrometry, 7,8 infrared spectrometry, 9 solvent variation, 8 conductance measurement, 10 light-scattering and vapor pressure osmometry, 11 nuclear magnetic resonance, 3,12 as well as thermal analysis and microscopy. 13,14 Some theoretical tools have also been attempted, such as molecular orbital calculations.…”