Thermochemical Transition in Low Molecular Weight Substances: The Example of the Silybin Flavonoid

Abstract

Silybin is a complex organic molecule with high bioactivity, extracted from the plant Silybum. As a pharmaceutical substance, silybin’s bioactivity has drawn considerable attention, while its other properties, e.g., thermodynamic properties and thermal stability, have been less studied. Silybin has been reported to exhibit a melting point, and values for its heat of fusion have been provided. In this work, differential scanning calorimetry, thermogravimetry including derivative thermogravimetry, infrared spectroscopy, and microscopy were used to provide evidence that silybin exhibits a thermochemical transition, i.e., softening occurring simultaneously with decomposition. Data from the available literature in combination with critical discussion of the results in a general framework suggest that thermochemical transition is a broad effect exhibited by various forms of matter (small molecules, macromolecules, natural, synthetic, organic, inorganic). The increased formation of hydrogen bonding contributes to this behavior through a dual influence: (a) inhibition of melting and (b) facilitation of decomposition due to weakening of chemical bonds.

On the Thermodynamic Thermal Properties of Quercetin and Similar Pharmaceuticals

“…In this temperature range, the mass loss of quercetin dihydrate was 7–8 wt.%, and at 130 °C fluidization occurred [ 12 ]. This behavior is pretty similar to the one that has been reported recently for silybin [ 14 ], thus, this effect in quercetin dihydrate seems to be a thermochemical transition. The quercetin used in the current study is not the dihydrate form and exhibits a much lower mass loss (0.9 ± 0.3 wt.%) around 100 °C (these values were calculated from three independent repetitions of the TGA measurements).…”

“…However, this is not always the case, e.g., for gallic acid [ 15 ]. Besides these factors, the absence of mass loss after this first minor decomposition step for a broad temperature range (e.g., for silybin, no mass loss has been detected in the range 180–260 °C [ 14 ], or for quercetin as presented in the current study) also contributes to the confusion regarding the phase behavior of flavonoids and other pharmaceuticals. Regarding modelling and the difficulty in the prediction of the thermodynamic properties of such molecules, it can be concluded that besides the structure and intermolecular interactions, the strength of chemical bonds and their weakening due to various factors should be taken into account.…”

“…Of course, the physical meaningfulness of this value is highly questionable. For various reasons (not volatile decomposition products that are not detected as mass loss in the TGA and uncertainty of the heat measured by the DSC due to an alteration of the heat capacity baseline due to mass loss), which have been discussed recently in detail [ 9 , 14 ], the uncertainty for the specific heat of a thermochemical transition is quite high, and the presented values should not be considered as accurate values. On the contrary, more attention should be given to their order of magnitude.…”

“…In addition, variation in the reported values of succinic acid’s melting point has been suspected to arise from the decomposition and/or acid dehydration and formation of anhydride upon heating [ 13 ]. Very recently, the thermal transition of the flavonoid silybin was recognized as a thermochemical transition, which was erroneously considered as melting [ 14 ]. For gallic acid, two thermochemical transitions were reported, namely a solid–solid and solid–liquid thermochemical transitions [ 15 ].…”

Thermochemical Transition in Non-Hydrogen-Bonded Polymers and Theory of Latent Decomposition

“…Almost simultaneously with the above mentioned studies regarding polymers, the thermochemical transition was also reported to occur in some low molecular weight substances, namely two flavonoids (silybin [ 15 ] and quercetin [ 16 ]) and gallic acid [ 17 ]. It was reported [ 16 ] that the thermochemical transition is the “connection” among three different aspects [ 16 ].…”