Labeled molecules

When a molecule adsorbs to a surface, it can remain intact or it may dissociate. Dissociative chemisorption is conmion for many types of molecules, particularly if all of the electrons in the molecule are tied up so that there are no electrons available for bonding to the surface without dissociation. Often, a molecule will dissociate upon adsorption, and then recombine and desorb intact when the sample is heated. In this case, dissociative chemisorption can be detected with TPD by employing isotopically labelled molecules. If mixing occurs during the adsorption/desorption sequence, it indicates that the mitial adsorption was dissociative. 

The study of the infrared spectrum of thiazole under various physical states (solid, liquid, vapor, in solution) by Sbrana et al. (202) and a similar study, extended to isotopically labeled molecules, by Davidovics et al. (203, 204), gave the symmetry properties of the main vibrations of the thiazole molecule. More recently, the calculation of the normal modes of vibration of the molecule defined a force field for it and confirmed quantitatively the preceeding assignments (205, 206). 

In all the preceding studies, the active species was supposed to be R OH however, later, many authors, using labelled molecules, considered that it is the protonated acid RC(OH) instead. 

Because sugars are involved in most of the mechanisms established for the synthesis of these heterocycles, the development of carbohydrate chemistry has been most helpful in these researches—especially for the preparation of specifically labeled molecules. Conversely, the contribution of these efforts to carbohydrate chemistry and biochemistry has shown the involvement in biosynthesis of 1 -deoxy-D-f/rreo-pentulose—scarcely before recognized and considered a rare sugar—and of fully functionalized pentuloses of still unknown configuration (or their phosphates). Finally, evidence has been found in prokaryotes for a most extraordinary transformation of 5-amino-l-(P-D-ribofuranosyl)imidazole 5 -phos-phate into a pyrimidine. Surely, this transformation should be explained in terms... 

In a number of experimental studies of polymer diffusion, molar mass exponents close to 2 have been found, though always with some deviations. For example, using radio-labelled molecules, the diffusion coefficient of polystyrene in dibutyl phthalate was found to follow the relationship... 

The substrate molecules may become labeled with deuterium by rapid hydrogen exchange, and then the newly labeled molecule may become cleaved in the rate-determining step. 

An isotope that is used extensively is deuterium (heavy hydrogen), often in the form of a deuteromethyl (-CD3) group. The molecular weight of this compound is thus three Da higher than the unlabelled precursor and this is often sufficient to ensure that the ions in the molecular ion region of the unlabelled compound do not occur at the same m/z ratios as those from the labelled molecule. 

Formation of labeled molecules has been studied in a few cases, but has not been exploited usefully. Various radioactive organomercury compounds have been prepared diphenylmercury (33, 90), fluorescein (53), and chloromeredrin (43). A number of other potentially useful syntheses could doubtless be developed with a wide variety of nuclides with easily detectable y-rays—pharmaceuticals, pesticides, physiological tracers, oil-soluble markers for labeling oil shipments, and so on—if it could be established what molecules are of interest to the various consumers ... 

Yeom and Frei [96] showed that irradiation at 266 nm of TS-1 loaded with CO and CH3OH gas at 173 K gave methyl formate as the main product. The photoreaction was monitored in situ by FT-IR spectroscopy and was attributed to reduction of CO at LMCT-excited framework Ti centers (see Sect. 3.2) under concurrent oxidation of methanol. Infrared product analysis based on experiments with isotopically labeled molecules revealed that carbon monoxide is incorporated into the ester as a carbonyl moiety. The authors proposed that CO is photoreduced by transient Ti + to HCO radical in the primary redox step. This finding opens up the possibility for synthetic chemistry of carbon monoxide in transition metal materials by photoactivation of framework metal centers. 

Direct observation of molecular diffusion is the most powerful approach to evaluate the bilayer fluidity and molecular diffusivity. Recent advances in optics and CCD devices enable us to detect and track the diffusive motion of a single molecule with an optical microscope. Usually, a fluorescent dye, gold nanoparticle, or fluorescent microsphere is used to label the target molecule in order to visualize it in the microscope [31-33]. By tracking the diffusive motion of the labeled-molecule in an artificial lipid bilayer, random Brownian motion was clearly observed (Figure 13.3) [31]. As already mentioned, the artificial lipid bilayer can be treated as a two-dimensional fluid. Thus, an analysis for a two-dimensional random walk can be applied. Each trajectory observed on the microscope is then numerically analyzed by a simple relationship between the displacement, r, and time interval, T,... 

Rotational-echo double-resonance (REDOR)(75,79) is a new solid-state NMR technique which is sensitive to through-space carbon-nitrogen interactions between selectively 13C and 15N-enriched sites separated by up to 5A (20-22). The parameter directly measured in a REDOR experiment is the heteronuclear dipolar coupling constant DCN, which is in itself proportional to the inverse third power of the intemuclear distance, rCN. It is this dependence on (icn)3 which accounts both for REDOR s ability to accurately measure short distances and its insensitivity to longer-range interactions. As a technique which can probe, in detail, intermolecular interactions over a distance range of 5A, REDOR is well suited to studying the distribution of small selectively-labeled molecules in polymer delivery systems. 

The self-diffusion coefficient is determined by measuring the diffusion rate of the labeled molecules in systems of uniform chemical composition. This is a true measure of the diffusional mobility of the subject species and is not complicated by bulk flow. It should be pointed out that this quantity differs from the intrinsic diffusion coefficient in that a chemical potential gradient exists in systems where diffusion takes place. It can be shown that the self-diffusion coefficient, Di, is related to the intrinsic diffusion coefficient, Df, by... 

However, NMR spectrometers use deuterium signals from deuterium-labelled molecules to keep them stable such substances are known as lock substances and are generally used in the form of solvents, the most common being deuterochloroform CDC13. 

Cyanine dyes have the common molecular formula R2N [CH=CH]nCH=N+R2 where the mono- or poly-methine chain is flanked by two nitrogen atoms that form part of a heterocyclic system (see Fig. 6.6). The most common cyanine derivatives used for labeling molecules are Cy3 and Cy5. These are symmetrical... 

Komatsu, T., Kikuchi, K., Takakusa, H., Hanaoka, K., Ueno, T., Kamiya, M., Urano, Y. and Nagano, T. (2006). Design and synthesis of an enzyme activity-based labeling molecule with fluorescence spectral change. J. Am. Chem. Soc. 128, 15946-15947. 

---