Molecular dynamics and crystallization phenomenon of supercooled and glassy DNA and RNA nucleosides:β-adenosine,β-thymidine, andβ-uridine

Abstract

Nucleosides are chemical compounds that have an extremely important biological role; they can be found in all types of living organisms. They are crucial components from which DNA and RNA acids are built. In addition, nucleosides are key regulators of many physiological processes. In this paper, the molecular dynamics in the liquid and glassy state of three selected nucleosides, β-adenosine, β-thymidine, and β-uridine, was investigated by means of dielectric spectroscopy. Our results revealed multiple relaxation processes associated with different types of molecular motions. Besides the primary α relaxation, two secondary modes in the glassy states of examined compounds were identified. Crystallization progress monitored by dielectric spectroscopy and x-ray diffraction technique at isostructural relaxation conditions revealed that the examined nucleosides possess completely different tendencies to recrystallize from the liquid as well as the glassy state. We have also made an attempt to predict the time scale of molecular motion below the glass transition temperatures of the respective nucleosides to discuss their potential stability at room temperature over prolonged storage time. Finally, combination of molecular mobility studies with evaluation of thermodynamic parameters from calorimetric measurements allowed us to discuss the fundamental roles of both kinetic and thermodynamic factors in governing the physical stability of the glassy state.

Tuning the Kinetic Stability of the Amorphous Phase of the Chloramphenicol Antibiotic

“…It can be seen that the relaxation strength of the α process scales as 1/ T , as expected from the Kirkwood–Fröhlich equation . The secondary relaxation is a simply activated process, following the Arrhenius law with activation energy E a = 38.0 ± 0.6 kJ/mol, a relatively low value that is close to that reported in ref and which suggests an intramolecular origin of this relaxation process, as also discussed below. Instead, the temperature dependence of the α relaxation time could be modeled with a Vogel–Fulcher–Tamman (VFT) function, defined by where τ ∞ is the high temperature limit of the relaxation time, D is the so-called strength parameter (proportional to the inverse of the fragility index, see below), and T 0 is the Vogel–Fulcher temperature, whose value indicates the departure from a simply activated behavior.…”

Secondary relaxation dynamics in rigid glass-forming molecular liquids with related structures

“…4(b). 19,22,23,[39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] It was noted before that the aforementioned relation of activation energy to T g is not universal. 41 Many true JG β-relaxations, not shown in Fig.…”

“…The relationships between α-relaxation and JG β-relaxation times had been established by the CM 7,9,10,58 and are consistent with the results from considerable number of experimental studies in many glass-forming systems. 7,[9][10][11][12]14,15,17,[19][20][21][22][23]27,28,[30][31][32][33]39,40,44,47,48,53,56,57 One relation showed that the dynamic separation between the αand the JG β-relaxations depends on the coupling parameter n (n ≡ (1 − β KWW )), and it is given by…”

Can Storage Time Improve the Physical Stability of Amorphous Pharmaceuticals with Tautomerization Ability Exposed to Compression? The Case of a Chloramphenicol Drug

“…Usually, secondary relaxation processes originating from the local motions of the entire molecule (i.e., JG processes) have a significantly greater energy barrier. For example, the E a of the intermolecular (JG) secondary relaxation of β-adenosine, β-uridine, celecoxib, and telmisartan are equal to 80, 77, 80, and 82 kJ/mol, respectively …”

“…For example, the E a of the intermolecular (JG) secondary relaxation of β-adenosine, β-uridine, celecoxib, and telmisartan are equal to 80, 77, 80, and 82 kJ/mol, respectively. 39 In order to parametrize the temperature dependence of the CLP's structural (α) relaxation time revealing a non-Arrhenius behavior (see squares on Figure 5), we employed the Vogel− Fulcher−Tammann (VFT) equation 40−42…”