Untitled

Abstract

Both CCD Raman and NIR spectroscopic methods can be applied to monitoring of hydrate formation processes. However, NIR is more suitable for monitoring solid-water interactions.

Computationally‐Assisted Approach to the Vibrational Spectra of Molecular Crystals: Study of Hydrogen‐Bonding and Pseudo‐Polymorphism

“…The exception is the methyl group at position N (3) , which does not participate in any hydrogen bond neither in the hydrate structure nor in the anhydrous structure. A characteristic feature of the monohydrated structure is the existence of heaped layers of dimeric structures of TP molecules, related by a centre of symmetry, which are held together by two types of TP···TP interactions, namely N (7) ÀH···O (6) and C (8) ÀH···O (2) (each TP molecule establishing two equivalent interactions of each type, thus acting both as a donor and as an acceptor). In addition, each TP molecule establishes two types of TP···H 2 O interactions (N (9) ···HÀO w and C (1) ÀH···O w ), forming water network channels that cross the different TP molecular layers.…”

“…Molecular pair II, which presents two strong N (7) -H···O (6) interactions, corresponds to the lowest energy minimum found. The predicted NÀH···O distance is 177 ppm, which is in good agreement with the reported X-ray value, 190 ppm, [29] taking into account the distinct nature of the two methods.…”

“…[5] It is well documented that CA and TP are sensitive to polymorphic and pseudo-polymorphic transformations that affect their dissolution profiles and, consequently, their bioavailability. [6][7][8][9][10][11] In fact, they crystallize into different states (hydrate and anhydrous) [12][13][14][15] and are good model compounds for the accurate characterization of both the polymorphic form and hydration states.…”

“…[6,[16][17][18][19][20][21][22] However, to the best of our knowledge, no complete vibrational assignment has been attempted yet and the complete and reliable assignment of the vibrational spectra of these compounds is naturally justified. Very recently some works showed the vibrational spectra of CA, TP, and TB, [6,12,[19][20][21]23] but, unfortunately, including incomplete, questionable and even misleading assignments, as reported previously by some of us. [22] The complete assignment of the vibrational spectra of relatively complex molecules in the crystalline state is quite difficult, and the assignment of some experimentally observed bands to specific vibrations is usually uncertain.…”

“…Molecular pair I represents the intermolecular contacts characteristic of the TPa form (TP dimer structures held by N (7) À H···N (9) interactions), while molecular pairs II, III, IV, and V represent the four distinct molecular associations that are evident in the TPh crystal structure (molecular associations held through N (7) ÀH···O (6) and C (8) ÀH···O (2) , N (9 ···HÀO w and C (1) ÀH···O w interactions). Molecular pair II, which presents two strong N (7) -H···O (6) interactions, corresponds to the lowest energy minimum found.…”