Formulation support spectroscopy

Raman spectroscopy is emerging as a powerful analytical tool in the pharmaceutical industry, both in PAT and in qualitative and quantitative analyses of pharmaceuticals. Reviews of analyses of pharmaceuticals by Raman spectroscopy have been published.158 159 Applications include identification of raw materials, quantification of APIs in different formulations, polymorphic screening, and support of chemical development process scale-up. Recently published applications of Raman spectroscopy in high-throughput pharmaceutical analyses include determination of APIs in pharmaceutical liquids,160,161 suspensions,162 163 ointments,164 gel and patch formulations,165 and tablets and capsules.166-172... 

The observed unidirectional (no reversal of rotation) and discrete rotation of the y subunit in steps of 120° during ATP hydrolysis by single molecule spectroscopy [34,35,40] supports the irreversible mode of operation of a single enzyme molecule that has been envisaged for the formulation of the thermody-... 

Both bis and tris ethylenediamine complexes have been described 12 the latter have been formulated [Sc(en)3]X3 (X=C1 or Br), this being supported by IR data. Heating in vacuum leads to formation of c -[ScX2(en)2]X. A number of complexes qf ScCl3 with primary and secondary amines, mainly aliphatic, have been prepared and their thermochemistry and IR spectroscopy studied.13-15 The compounds are ScCl3 (RR NH), where n = 1-4 and R = R = Me, Et, Pr, Bu or Pe or R = H and R1 - Et, Pr, Bu, Pe, phenyl, benzyl or 2-naphthyl. Further investigation would be necessary to establish the structural nature of these complexes. 

Methylselenophene-2-thiol and 2,5-dimethylselenophene-3-thiol have been shown to exist as thiols by NMR and IR spectroscopy as well as by comparison of gas phase ionization potentials with those of appropriate model compounds (77ACS(B)198). Dipole moment studies have supported formulation of selenophene-2- and -3-thiols as such (73BSF1924) rather than the 2-thione structure originally proposed for the former compound (71BSF3547). 

In general, there is no strong evidence to support homoaromatic formulations of the structures of any of these systems. There are indications from PE spectroscopy of some degree of interaction between the unsaturated fragments of these molecules. However, as we have pointed out, PE spectroscopy as a technique has limited value in probing homoaromaticity. Magnetic evidence has either not been examined in detail in most systems or, where chemical shifts have been examined, is not definitive. Thermochemical... 

It is in the development and support of formulated products that Raman spectroscopy probably has most to offer the life cycle of a pharmaceutically active molecule. Due to there being few limitations to sample presentation prior to analysis, Raman spectroscopy is particularly versatile and can be applied to both macro- and microsamples. 

However, spectroscopic studies of activated BLM indicate that it is not an Fev=0 species. It exhibits an S - 1/2 EPR spectrum with g values at 2.26, 2.17, and 1.94 [15], which is typical of a low-spin Fe111 center. This low-spin Fem designation is corroborated by Mossbauer and x-ray absorption spectroscopy [16,19], Furthermore, EXAFS studies on activated BLM show no evidence for a short Fe—0 distance, which would be expected for an iron-oxo moiety [19], These spectroscopic results suggest that activated BLM is a low-spin iron(III) peroxide complex, so the two oxidizing equivalents needed for the oxidation chemistry would be localized on the dioxygen moiety, instead of on the metal center. This Fe(III)BLM—OOH formulation has been recently confirmed by electrospray ionization mass spectrometry [20] and is supported by the characterization of related synthetic low-spin iron(III) peroxide species, e.g., [Fe(pma)02]+ [21] and [Fe(N4py)OOH]2+ [22], The question then arises whether the peroxide intermediate is itself the oxidant in these reactions or the precursor to a short-lived iron-oxo species that effects the cytochrome P-450-like transformations. This remains an open question and the subject of continuing interest. 

A criterion for the suitability of a spectroscopy cell for investigations of working catalysts can be formulated as follows the activity or selectivity data and activation energy values have to be in agreement with the catalytic performance data measured with a conventional fixed-bed reactor. Table 1 is a comparison of the conversion and selectivity values characterizing an alumina-supported molybdenum-vanadium oxide catalyst during propane ODH obtained with a conventional fixed-bed reactor and with a spectroscopic cell that fulfills this requirement (Banares and Khatib, 2004). Similar considerations have also been reported earlier for other methods, such as X-ray diffraction (Clausen et al., 1991). 

Proton NMR studies of aqueous arsenious acid solutions show only a single proton resonance attributable to arsenious acid. This result together with Raman spectroscopy suggest the species having a pyramidal structure which can be formulated as As(OH)3. This is to be contrasted with H3PO3, which is HP(0)(0H)2 with four-coordinate phosphorus and which exhibits two distinct proton NMR resonances. Spectroscopic evidence supports the formation of the three anions [H2ASO3], [HAsOs] ", and [AsOs] when solutions of As(OH)3 are treated with hydroxide ion. This observation agrees with a three-step acid dissociation. The pA a for the dissociation of the first proton is 9.2, which means that H3 AsOs is a very weak acid. 

The conclusion that the cobalt and iron complexes 2.182 and 2.183 are formally TT-radical species is supported by a wealth of spectroscopic evidence. For instance, the H NMR spectrum of the cobalt complex 2.182 indicated the presence of a paramagnetic system with resonances that are consistent with the proposed cobalt(III) formulation (as opposed to a low-spin, paramagnetic cobalt(IV) corrole). Further, the UV-vis absorption spectrum recorded for complex 2.182 was found to be remarkably similar to those of porphyrin 7r-radicals. In the case of the iron complex 2.183, Mdssbauer spectroscopy was used to confirm the assignment of the complex as having a formally tetravalent metal and a vr-radical carbon skeleton. Here, measurements at 120 K revealed that the formal removal of one electron from the neutral species 2.177 had very little effect on the Mdssbauer spectrum. This was interpreted as an indication that oxidation had occurred at the corrole ligand, and not at the metal center. Had metal oxidation occurred, more dramatic differences in the Mdssbauer spectrum would have been observed. 

Infrared spectral data91 have been advanced to support the oxo formulation for 96 (R = propyl). Structure 96 (R = phenyl) has also been proposed on the basis of the fact that benzoin does not condense with urea,105 and this conclusion is probably correct, although the argument is not convincing. The oxo forms of benzimidazolone, 97 106,107 an(j related pyrazinoimidazolone 98107 have been shown to predominate using infrared spectroscopy. Ultraviolet spectral comparisons indicate that 99 exists largely in the oxo form.108 The only... 

This paper presents studies of solid state polymerization aimed towards formulating a dynamic model of reactivity in the condensed phase. Phonon spectroscopy is successfully used to elucidate the mechanism of lattice control of the reaction. Novel concepts of phonon-assisted thermal and photochemical reactions are introduced, supported by experimental data. Non-linear laser spectroscopy is used to find the importance of biexcitonic processes in photopolymerization. Also, spectroscopic studies of reactions in Langmuir-Blodgett films and at gas-solid interface which produce ordered polymers are presented. 

On the basis of product studies, it is clear that irradiation of the naphthyl azides leads to loss of nitrogen with the likely consequent formation of nitrenes. Just as for phenyl azide, the initially formed singlet nitrenes may intersystem cross to the triplet and then dimerize to azo compounds. Clearly in the case of 2-naphthyl azide, but not 1-naphthyl azide, a closed-shell ground-state intermediate that can be trapped with diethylamine can be generated. The intermediate was formulated as the azirine on the basis of product studies [57]. Low temperature absorption spectroscopy and time-resolved laser flash photolysis experiments to be described later support the formation of azirines and provide an explanation for the different reactivity observed between the 1- and 2-substituted azides. 

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