Understanding the Role of Temperature Change and the Presence of NaCl Salts on Caffeine Aggregation in Aqueous Solution: From Structural and Thermodynamics Point of View

Abstract

To examine the molecular level understanding of temperature induced self-association of caffeine molecules in aqueous solution both in the presence and absence of salt NaCl, we have performed long MD simulations at a regime of temperatures ranging from 275 to 350 K with a temperature difference of 25 K. The calculations of different site-site radial distribution functions followed by coordination number analyses, the calculations of preferential interaction parameters, solvent accessible surface area, and cluster structure analyses show a depletion in the caffeine association propensity with increasing temperature. We have also observed the salting out effect of caffeine molecules in salt solution. The simultaneous presence of polar and nonpolar groups in a caffeine molecule leads to anisotropic hydration. Specifically, the hydration tendency of caffeine hydrophobic sites increases with increasing temperature, while hydrophilic sites tend to be less hydrated. This leads to a decrease in caffeine association. In accordance with some experimental studies on thermodynamics of caffeine association, we have also observed enthalpy driven association in pure water. But the presence of salt leads to entropy driven association specifically at higher temperature. This is due to the relatively stronger interactions of salt ions with caffeine at higher temperature.

Volumetric, Viscometric and Spectroscopic Approach to Study the Solvation Behavior of Xanthine Drugs in Aqueous Solutions of NaCl at T = 288.15–318.15 K and at p = 101.325 kPa

“…This may be due to the presence of both hydrophilic and hydrophobic groups in the solutes structures and thus these solutes show different hydration pattern. As mentioned in the literature, the higher the molality of aqueous NaCl solutions, the greater is the association between the CAF molecules, which reduce the accessibility of CAF hydrophilic groups for water molecules. In other words, the addition of salt causes an exclusion of water from the CAF hydrophilic sites, and hydrophobic sites tend to be more hydrated.…”

Underlying Mechanisms of Allopurinol in Eliminating Renal Toxicity Induced by Melamine–Uric Acid Complex Formation: A Computational Study

“…In the current study, the preferential interaction parameters, τ ua u (UA-UA over UA-AP), τ au a (AP-AP over AP-UA), and τ ua m (MM-UA over MM-AP) are determined, and these are generated for systems S0S3 following the equations shown below: ,− where a , m , and u denote AP, MM, and UA molecules, respectively, and ρ u and ρ a represent the number density of UA and AP molecules, respectively. The preferable interaction between any two molecules (say i and j ) can be indicated with the higher positive value of τ than any other interactions.…”

“…The preferable interaction between any two molecules (say i and j ) can be indicated with the higher positive value of τ than any other interactions. Here, G ua , G uu , G aa , G mu , G ma , and G au correspond to Kirkwood–Buff integrals, and these integrals can be accessed following earlier studies. ,− It ought to be referenced that these integrals can be accomplished with the accompanying radial distribution functions. The centers of mass (COMs) of any two molecules are considered for appraising these distribution functions.…”

Volumetric, Viscometric, and1H NMR Studies on Caffeine, Theophylline, and Theobromine in Aqueous Solutions of MgCl2at TemperaturesT= (288.15 to 318.15) K and at Pressurep= 101.3 kPa

“…Therefore, maximum hydrophobic interactions are observed in the case of CAF. Sharma and Paul reported the salting out effect of CAF molecules in salt solution, as they have observed strong interactions of salt ions with CAF at higher temperatures. , When a solute, for example, a drug, is dissolved in water, it becomes hydrated/solvated according to its hydrophilicity or hydrophobicity. Upon the addition of another solute, such as an electrolyte, into this (water+drug) system, the solubility of the drug may increase or decrease, depending upon the nature of the electrolyte, because of its salting-in/salting-out effect.…”