Isotopic isomers

Molecules which differ from each other only because one or more nuclei in one molecule have been replaced by a different isotope of that nucleus are referred to as isotopic isomers or isotopomers. Born and Oppenheimer (1927) were the first to... 

Obviously, there is an isotope effect on the vibrational frequency v . For het-eroatomic molecules (e.g. HC1 and DC1), infrared spectroscopy permits the experimental observation of the molecular frequencies for two isotopomers. What does one learn from the experimental observation of the diatomic molecule frequencies of HC1 and DC1 To the extent that the theoretical consequences of the Born-Oppenheimer Approximation have been correctly developed here, one can deduce the diatomic molecule force constant f from either observation and the force constant will be independent of whether HC1 or DC1 was employed and, for that matter, which isotope of chlorine corresponded to the measurement as long as the masses of the relevant isotopes are known. Thus, from the point of view of isotope effects, the study of vibrational frequencies of isotopic isomers of diatomic molecules is a study involving the confirmation of the Born-Oppenheimer Approximation. 

Fig. 5.6 Vapor pressure differences between equivalent isotopic isomers of dideuteroethylene. The three mercury levels shown (left to right) measure the vapor pressures of ordinary ethylene C2D4, /ram-ethylene-1,2dj, and ei.v-cthylene- l dj. The vapor pressure of gem-ethylene-1,ld2 is very similar to the cis-isotopomer and is not shown in this photograph (Bigeleisen, J., Science 147, 463 (1965))...

The difference in the electron affinity between light and heavy isotopic isomers is, in other words, the difference in the stability of their anion-radicals. Such a difference gives a valuable tool for use in probing the chemistry of anion-radicals. The difference in the stability of the ring-deuterated and ring-nondeuterated arene anion-radicals has been employed to examine the transition states for the one-electron-promoted cleavage of naphthyl methyl phenyl ether and naphthyl benzyl ether (Guthrie and Shi 1990). In this reaction, the potassium salt of fluoranthene anion-radical was an electron donor ... 

An analytical chemical technique that utilizes radioactive (or stable) isotopes for the quantitative analysis of the amount of substance. In the absence of a kinetic isotope effect, isotopic isomers react identically with respect to their unlabeled counterparts. The method offers the advantage that specific activity (or gram-atom excess in the case of stable isotopes) is an intensive variable. Therefore, one only needs to recover sufficient labeled metabolite to determine amount of substance and disintegrations per minute (or, gram-atom excess) to reach an accurate determination of specific activity. The technique is feasible so long as one can accurately determine the initial and final specific activities. 

These estimations engage the assumption that any additional effects due to bending vibrations will tend to contribute relatively weakly to the isotope effect. In fact, however, the above estimates are probably only ball park estimates, in that coupling of molecular vibrations of multiatomic molecules is ignored Another key point is that a covalent bond need not be completely broken in the transition state, and two isotopic isomers may behave slightly differently in the transition state. Jencks discusses this matter as well as the problem of nonlinear transition states, a condition that takes into account the fact that bending frequencies often lessen the developed magnitude of isotope effects. 

Examination of one real-life case may benefit the reader s understanding. Strittmatter studied the primary kinetic isotope effects arising in the NADH-dependent cytochrome bs reductase (EC 1.6.2.2). The oxidation of NADH and subsequent reduction of cytochrome bs is facilitated by the enzyme-bound FAD group, and the kinetics of the direct transfer of a hydrogen from the A-face (or pro-R) of NADH to the flavin can be monitored by the loss of the 340 run absorbance of the NADH s dihydropyridine ring. Using deuterated isotopic isomers of NADH and several related compounds, Strittmatter obtained the primary kinetic isotope effect data compiled in the table below. 

As a result of metabolic reactions an isotope may appear at more than one position in a product, yielding two or more isotope isomers or isotopomers. These are seen individually by NMR spectroscopy and the concentration and isotope labeling patterns of the labeled compounds can be followed over a period of time. The use of this isotopomer analysis in studies of the citric acid cycle is illustrated in Box 17-C and its use in studies of glucose metabolism is considered in Chapter 17, Section L. 

For Re2(02CC Hs)4Cl2 the first reduction wave near —0.3 V is quasi-reversible. The product of this one-electron oxidation was not isolated as a solid, but ESR spectra were obtained on frozen dichloromethane solutions at 77°K at both X- and Q-band frequencies. Both naturally occurring rhenium isotopes have a nuclear spin of 5/2 with slightly different nuclear magnetic moments. For dimeric rhenium species there are three distinct isotopic isomers and each generates a unique ESR spectrum as a result of differing hyperfine interactions. The observed ESR spectrum is a superposition of these lines with the intensity... 

A more extensive study of mobilities of 3H- and 14C-labeled amino acids again found that amino acids labeled with 14C at Cl or C2 are retained on the column, relative to the unlabeled forms.135 Lysine is an exception. Tritiation at C3 also increases the retention time, but tritiation at C2 of glycine or at C4, C5, or C6 of lysine decreases it, and large decreases are seen with methionine tritium-labeled in the methyl and with tyrosine tritium-labeled at C3, 5. The 14C IEs can be attributed to a decrease of acidity, but the IEs of distant 3H may be due to hydrophobic interactions with the resin. A remarkable result is that intramolecular isotopic isomers (isotopomers) can be distinguished on the basis of their chromatographic mobilities. 

Isomers Two isotopes that have the same atomic (Z) and mass numbers (A), but their nuclei are in different energy states. Isotope isomers are labeled m , or q with increasing excitation energy (Audi et al.,... 

Pochan, Baldwin and Flygare have analyzed the microwave spectra of cyclopropanone and the isotopic isomers 13Ci, 13C2, and 2,2-dideutero-cyclopropanone.63) The rotational transitions were determined by studying the Stark effect (the shifts and splittings of lines produced by an electric field). The type of transition observed for cyclopropanone was consistent with C v symmetry and the sum of the moments of inertia (/a + /b — Ic) suggested that all four protons are out-of-plane. These data eliminate such structural alternatives as the dipolar oxyallyl tautomer 82 and allene oxide 83. The electric dipole moment (fi ) was calculated to be 2.67 0.10 D, which corresponds to an average of those of acetone (2.93 D) 65> and formaldehyde (2.34D).6 )... 

Figure 3 shows the effect of applied magnetic field on the cage effect for 1 and some of Its Isotopic Isomers. The higher cage effect for enriched ketone (compound 8 in Figure 3) cor-... 

Since the samples contained three isotopic isomers with potential variation in enrichment at each position aU three positions needed to be measured separately for each data point. However because of the nature of the structure of the molecule and the resultant fragmentation patterns, none of the three positions could be measured without interference from one or both of the other two. The use of other derivatives, such as the butyl-boronate or trl- methylsUyl derivatives, did not improve this situation. Thus, corrections for the interfering enrichments needed to be made. Both (70eV) electron Impact Ionization (El) and methane chemical ionization (Cl) were used to take advantage of particular fragments or enhanced signal abundances which occurred in each mode. 

Chromatographic separations of the isotopic isomers of molecules are of interest first because they afford a convenient technique for analysis of mixtures, secondly because scale up in the future might afford economically feasible separations of macroscopic amounts of material, and finally because the values of the separation factors and their temperature coefficients are of intrinsic theoretical interest. This last follows because such data are straightforwardly related to the understanding of isotope effects on solution and adsorption processes and of the intermolecular forces which give rise to these effects. We have approached the general problem... 

From a more practical standpoint it is clear that chromatographic techniques afford a cheap, rapid, and convenient method for the analysis of mixtures of isotopic molecules. Also preparative scale chromatography might in the future afford one route towards isolating useful amounts of isotopic isomers which are diflScult or impossible to synthesize as pure compounds. 

By use of tracer experiments, Clusius ° showed that branched pathways are involved in this reaction nitrosation of phenylhydrazine with N-labelled nitrous acid produced two isotopic isomers of phenyl azide (274) and (275) (equation 143). 

In a more detailed examination of the mechanism, Clusius and Schwarzenbach found that the same mixture of isotopic isomers arises both from diazotization of phenylhydrazine with labelled nitrous acid and from dehydration of specifically labelled a-nitroso-phenylhydrazine (276). It was concluded that a-nitrosophenylhydra-... 

---