Spectroscopic data from various techniques

Each of the various types of spectroscopy that can be applied to the determination of an impurity or degradant structure allows an investigator many choices and considerable flexibility. Not all of the various types of experiments that can be performed should be done for any given isolate. Ideally, the team of scientists working on an impurity or degradant structure problem should try to select those experiments for their respective spectroscopic methods that will provide the most useful information. Then, if instrament time permits, additional experiments can 

Simple molecular weight changes relative to the parent molecule may indicate the gain or loss of the equivalent of a methylene group (i.e. the loss of a methyl group replaced by a proton), oxidation, and hydration/dehydration or hydrolysis to list only a few possibihties. The formation of adduct ions, for example, sodium, potassium, or acetonitrile at +23, +39, and +43 Da, respectively, can provide the means for the preliminary identification of the molecular ion of a molecule. Isotope patterns, for example, from Cl, and even can also be diagnosti- 

The order in which various NMR data are acquired is largely one of user preference. Acquisition of the proton reference spectrum will invariably be undertaken first. Whether a user next seeks to establish homo- or heteronuclear shift correlations is where individual preferences come into play. Many spectro-scopists proceed from the proton reference spectrum to either a COSY or a TOCS Y spectrum next, while others may prefer to establish direct proton-carbon chemical shift correlations. This author s preference is for the latter approach. From a multiplicity-edited HSQC spectrum you obtain not only the carbon chemical shifts, which give an indication of the location of heteroatoms, the degree of unsaturation and the like, but also the number of directly attached protons, which eliminates the need for the acquisition of a DEPT spectrum [51, 52]. The statement in the prior sentence presupposes, of course, that there the sensitivity losses associated with the acquisition of multiplicity-edited HSQC data are tolerable. 

Hyphenated NMR methods are not considered in the present chapter. The interested reader is referred to Chapter 6 or to one of the numerous reviews that have appeared recently that deal with various hyphenated NMR methods [40,61-63]. 

Contemporary approaches to chemical stmcture elucidation are now heavily reliant on mass spectrometry and NMR spectroscopy. Since the advent of 2D NMR methods, in many laboratories vibrational data are either not acquired or not considered, which represents a paradigm shift from approaches to chemical structure elucidation as recently as 20 years ago when vibrational spectroscopic data were an integral part of the structure elucidation data assembled to characterize an unknown structure. In contrast, we have found it useful to continue to acquire and utilize vibrational data for the characterization of impurities and degradation products [64,65]. 

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Despite the extensive studies of the anodic layers on Pt with various ultraviolet-visible optical methods, they have not provided a clear indication of the electronic or structural properties of the layers. Rather these optical methods have been more than just another form of readout to complement the electrochemical measurements of charge and current response of the layer to potential and time. Vibrational spectroscopic data from infrared and Raman measurements would be more helpful in establishing the nature of the layers but it is difficult to use these techniques to study metal-electrolyte and similar interfaces because of solvent interference and sensitivity problems. A noteworthy exception is the quite successful in situ use of Raman spectroscopy to study the electrochemically formed oxide layers on silver by Kotz and Yeager. In the instance of silver electrodes, there is a large surface enhanced Raman effect and the signal-to-noise ratio is not a problem. Unfortunately this is not the situation with other metal surfaces such as Pt. Even so, with improved instrumentation there is hope that in situ Raman studies of the anodic layers on Pt will become practical. 

Most of the force fields described in the literature and of interest for us involve potential constants derived more or less by trial-and-error techniques. Starting values for the constants were taken from various sources vibrational spectra, structural data of strain-free compounds (for reference parameters), microwave spectra (32) (rotational barriers), thermodynamic measurements (rotational barriers (33), nonbonded interactions (1)). As a consequence of the incomplete adjustment of force field parameters by trial-and-error methods, a multitude of force fields has emerged whose virtues and shortcomings are difficult to assess, and which depend on the demands of the various authors. In view of this, we shall not discuss numerical values of potential constants derived by trial-and-error methods but rather describe in some detail a least-squares procedure for the systematic optimisation of potential constants which has been developed by Lifson and Warshel some time ago (7 7). Other authors (34, 35) have used least-squares techniques for the optimisation of the parameters of nonbonded interactions from crystal data. Overend and Scherer had previously applied procedures of this kind for determining optimal force constants from vibrational spectroscopic data (36). 

The physical chemist of today has a wide variety of methods at his disposal for the experimental investigation of electronic structure and all of them have been used in attempts at obtaining evidence of the participation of outer d-orbitals in bonding. One such group of methods is constituted by the various techniques of radiofrequency spectroscopy, which have the advantage that they yield information about the molecule in its ground state. In this they have a distinct superiority over, say, electronic absorption spectra where it is necessary to consider both ground and excited states. Moreover much of the data derived from radiofrequency spectroscopic methods concerns essentially just one part of the molecule so that attention can be concentrated on those atoms of interest in whatever study happens to be under way. 

Time-resolved emission spectroscopy is gaining importance in the study of various chemical aspects of luminescent lanthanide and actinide ions in solution. Here, the author describes the theoretical background of this analytical technique and discusses potential applications. Changes in the solution composition and/or in the metal-ion inner coordination sphere induce modifications of the spectroscopic properties of the luminescent species. Both time-resolved spectra and luminescence decays convey useful information. Several models, which are commonly used to extract physico-chemical information from the spectroscopic data, are presented and critically compared. Applications of time-resolved emission spectroscopy are numerous and range from the characterization of the... 

Near-infrared (NIR) spectroscopy is becoming an important technique for pharmaceutical analysis. This spectroscopy is simple and easy because no sample preparation is required and samples are not destroyed. In the pharmaceutical industry, NIR spectroscopy has been used to determine several pharmaceutical properties, and a growing literature exists in this area. A variety of chemoinfometric and statistical techniques have been used to extract pharmaceutical information from raw spectroscopic data. Calibration models generated by multiple linear regression (MLR) analysis, principal component analysis, and partial least squares regression analysis have been used to evaluate various parameters. 

Methods of obtaining energy levels via various techniques are given below in the section Experimental Techniques. This section deals with methods and model limitations in the determination of potential constants and geometric parameters from the observed energy levels and other spectroscopic data. 

LC/NMR in various combinations with LC/UV-DAD, LC/MS, LC/MSMS, LC/IR, and/or LC/CD has been used in many applications related to the online identification of natural products. In this field, the challenge for hyphenated techniques is important since often the characterization of completely unknown molecules is required in very complex biological matrices. In this case, LC hyphenated techniques are used for the chemical evaluation of biologically active fractions or extracts and for dereplication purposes. As full structure assignment is often needed, all online spectroscopic data are taken into consideration. Most applications are performed in the stop-flow mode and extensive 2D NMR correlation experiments are measured. For unknown online determination the need for data is often mandatory. This type of information can be deduced from HSQC and HMBC indirect measurements and very recently it has been demonstrated that even direct measurements were possible in a crude plant extract. For this application the LC peak of interest was preconcentrated by trapping on SPE and the measurement was performed on a cryogenic flow... 

Pseudopotentials describe the interaction of a valence electron with the core of the atoms. They are known in the literature under various names, such as model potentials, effective core potentials,. Model potentials are generally parametrized from atomic spectroscopic data whereas effective core potentials and pseudopotentials are most often derived from ab initio calculations. There is a huge literature on the subject and several review articles. " The recent paper by Krauss and Stevens is recommended for an overall survey of the subject with applications and comparisons with all-electron calculations. The recent review paper of Pelissier et al is devoted to transition elements. In the following we shall only review the main characteristics of the determination of atomic pseudopotentials by the ab initio simulation techniques of Section II.B. 

The attenuated reflectance technique presents an excellent example of how radiation at sample surface can enhance signal-to-noise ratio. Details of general optics and reflectance techniques can be found in the classic text (10). This technique is used extensively to determine differences between the structure of polymers in surface and bulk phases. Commercial accessories make these spectroscopic experiments easy to perform, although quantitative analysis of the data remains difficult. Examples of ATR applications include chemical composition analysis of polymers, surface orientation resulting from various processing methods, and chemical or thermal degradation of polymers. For samples such as powders or poorly defined surfaces, the diffuse reflectance technique can be used (11). In addition, the photoacoustic technique has been used to probe surface structure and multilayer structure commonly found in polymer laminates (17). In all these cases, optical effects can complicate analysis of infrared spectra. Nevertheless, these data have proven very useful in analytical applications. 

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