US3506402A - Method and device for measuring the radioactivity of 14c- and/or 3h-marked compounds - Google Patents

Description

Aprll 14, 1970 s o 3,506,402

METHOD AND DEVICEFOR MEASURING THE RADIOACTIVITY 0F "c- AND/0R ll-MARKED COMPOUNDS Filed June 11, 1965 HELMUT F. SIMON IN V EN TOR.

United States Patent O 9 ,489 Int. Cl. G01n 31/00 US. Cl. 23-430 13 Claims ABSTRACT OF THE DISCLOSURE Technique for analysis of organic compounds of the type in which the compounds are marked or labeled with either radioactive carbon C) or tritium H) includes, for example: passing the mixture to be analyzed over a heated catalyst of zinc and nickel (preferably having temperature zones varying from about 350 C. to about 620 C.) as a continuous gas stream, before passing the resulting gaseous reaction products through a flowthrough radioactive detector, which measures the radioactivity of the reaction products and therefore of the original compounds. The nickel catalyst causes hydrogenating cracking of the higher molecular weight compounds into simpler volatile compounds, thereby preventing condensation in the radioactivity detector, while the conversion of aromatic compounds avoids false radioactivity measurements caused by the beta rays readily admitted by such compounds. Other disturbing constituents, such as the halogens, oxygen and sulfur chemically combine with the zinc, thereby removing these constituents from the organic compounds; organic compounds containing these and similar constituents may cause a quenching eflfect on the actual radioactivity by absorbing the emitted beta particles (electrons). The reaction chamber may include (downstream of the zinc-nickel catalyst) a silver reactant (preferably in the form of silver Wool) to remove any halogen hydrides which may be formed (from the zinc halides). Preferably the original compounds are separated prior to introduction to the catalytic reaction chamber, for example by means of an otherwise conventional gas chromatograph (utilizing a, say, thermal conductivity detector and a hydrogen carrier gas) before the now separated compounds reach the catalyst. 'In this manner both the quantity of individual components in the sample mixture and the radioactivity of each of those components which have been radioactively marked are measured, thereby yielding complete analytical data on the amounts and radioactivity of the various components of the original mixture.

The present invention relates to measuring the radioactivity of compounds which are marked or labelled with radioactive carbon C or tritium H. The invention relates more particularly to radio-gas chromatography, that is, gas chromatography in which the radioactivity of substances eluted from the chromatographic column is measured.

It is known to pass substances the radioactivity of which is to be measured through ionization chambers or proportional detectors, such as gas flow-through counting tubes. However the following difficulties arise with most substances:

(1) The substances may condense to a certain extent in the detector. The condensed radioactive substances continuously emit radiation which may mask or hide the 'ice radiation of subsequently eluted substances which may be more weakly radiating. This risk exists in particular with comparatively non-volatile compounds. It might be possible to avoid such condensation -by suitable heating of the counting tube. However, at the temperature required to accomplish this, the noise level of the counting tube would be increased disadvantageously by reduct on of the insulating quality. Besides, further undesirable eifects to be described hereinafter might occur.

(2) Most substances in their passage through counting tubes and ionization chambers, respectively, either show a strong quenching i.e. radiation present is only partly indicated, or pseudo-activity, i.e. radiation is simulated even by substances not labelled. These phenomena may possibly be explained as follows. In a counting tube ions and secondary electrons are produced by the emitted 3- rays. These secondary electrons are accelerated in the field and produce further ions and electrons, so that each emitted fi-particle produces an electron avalanche which may be amplified as an electric pulse and be counted. Some substances, however, catch fs-particles (electrons) or secondary electrons so that no electron avalanche can develop. This is the quenching effect. There, however, also exist substances which easily give oif electrons. Such electrons may then be accelerated in the field and may give rise to the production of secondary electrons and thus to an electron avalanche in a similar manner to soft fl-rays. This leads to pseudoactivity. Quenching of the type hereinbefore described may be, for instance, observed with compounds containing oxygen or halogen as well as those containing NO -SH-, or amino groups.

To avoid these undesirable phenomena it is known to burn the substances, the radioactivity or which is to be measured, prior to their introduction into the counting tube or the like. For C-marked compounds the radioactivity of the resulting CO may then be measured. Such CO does not condense and also does not show any quenching or pseudoactivity, For measuring H-marked compounds, however, two reactions are required to be carried out. On combustion water is produced containing the tritium. To measure this in the counting tube, the water must again be converted into another hydrogen or into useful compound. This requires quite a considerable amount of apparatus to perform these two chemical reactions successively and continuously. Also particularly disadvantageous is the phenomenon that in all methods of determination in which the tritium exists intermediately as HOT, so-called memory-effects arise. All surfaces contain a thin sheet or layer of water to a certain extent. If water in the form of T 0 or HOT flows across such a Wet surface, then an ion-exchange occurs in such manner that the tritium replaces hydrogen H in the water of the surface layer and is replaced in turn subsequently in a new exchange reaction by H from following normal water. Thus, a kind of ion-exchange chromatography occurs with the tritium, 'It is apparent that this phenomenon may considerably affect the measurement.

It is further known to cause H-marked compounds to be converted into the gaseous phase (except water containing tritium) by heating the substance together with water, zinc and nickel oxide for about 40 minutes in an evacuated sealed tube. This, however, is a discontinuous process requiring that the sample be collected. It requires a considerable amount of apparatus. Besides, it has hitherto not been possible to convert *C-marked compounds in this manner. See Simon and Berthold Die Messung weicher Beta-Strahler in der Gasphase (The Measurement of Soft Beta-Radiation in the Gas Phase) in Die Atomwirtschaft 10 (1962), 498-507.

It has also been previously suggested for measuring C-marked compounds to direct the same in a hydrogen stream at 788 F. (420 C.) across Raney nickel (see Drawert and Bachmann Neuere Methoden zur Trennung und kontinuierlichen Messung von C-Verbindungen in der Gasphase (Recent Methods of Separation and Continuous Measurement of 14C Compounds in the Gas Phase" Angew. Chem. 15 (1963), 717-722, in particular page 720 on the right side near the bottom). In this manner, higher-molecular and therefore less volatile compounds are cracked so that the risk of condensation of radioactive substances in the counting tube is reduced. However, this method is not suited to convert halogen-, nitrogen-, or sulphur-containing compounds in a satisfactory manner. It is also not capable of properly converting tritium-marked compounds into compounds which do not cause any disturbance in the measurement of the radioactivity.

It is the object of the present invention to provide a method and device whereby both *C- and H-marked compounds may be quickly and quantitatively converted into compounds which permit a measurement of the radioactivity in a radioactivity detector without the difficulties described earlier in this specification. The invention is applicable to analyses where only the total activity of a sample shall be measured. However, it is particularly advantageously used in radio-gas chromatography (i.e., gas chromatographic separation, followed by detection of the radioactivity of each of the separated gases).

As is well-known in conventional gas chromatography a substance mixture to be analyzed is flushed through a separating column in gaseous or vaporous form by a carrier gas stream. The different components of the mixture interact with a separating substance provided in the separating column, either such that the mixture components go partly into solution in a liquid separating substance (partition), or such that they are adsorbed by a solid separating substance. Depending on the intensity of the interaction the various components are delayed to a greater or lesser degree, so as to successively appear at the exit of the separating column Where they are indicated by a detector, such as a thermal conductivity detector and recorded by a recorder as bell shaped curves (peaks). Now, in radio-gas chromatography, behind the regular detector i arranged a device permitting the radioactivity of the different mixture components to be determined.

The invention starts from a method for measuring the radioactivity of C- and/or H-marked compounds wherein the substances are caused to react with zinc and nickel at elevated temperature and are converted into chemical compounds which do not interfere with the measurement of radioactivity, and are supplied to a detector for radioactive radiation. In contrast to the known method wherein these reactions take place discontinuously in a closed-off vessel (Die Atomwirtschaft, 10 (1962) page 498 and following) the present invention proposes that the substances are passed continuously in the gas stream across a catalyst of zinc and nickel for conversion and are then passed through the detector.

It has been shown that by this method both C- and H-marked compounds may be converted independently of their chemical composition in such a manner that an unobjectionable measurement of the radioactivity may take place. The products of conversion produced with the method of the invention are such that the aforementioned deleterious effects, i.e., condensation, quenching, pseudoactivity, or memory-effects do not occur. Conversion products of the reaction and hydrogen will substantially be obtained in a mixture of methane and hydrogen. By the method of the invention for instance the following and H-marked substances, respectively, were analyzed:

Water- H, nitromethane- H, toluene- C, toluene- H, propyl iodide- C, aceticand butyric acid- H, four different alkyl iodides- H, bromoacetic acid-l-C-methylester and bromoacetic acid-Z-C-methylester. Solvents were used which by themselves, would be strongly disturbing in counting tubes and ionization chambers, respectively (chloroform, toluene). In no case did disturbances occur by the not radioactively-marked solvents. With a mixture of CH NO -T with toluene and chloroform, respective ly in the ratio 1:4 between 2 and 35 .tl a linear relationship resulted between the quantity introduced and the radioactivity found.

All mentioned marked compounds with the exception of nitromethane- H show the same counting yield. By the example of bromoacetic ester-1 C and bromoacetic ester-2 0 it was demonstrated that the counting yield with one and the same compound is independent of in which chemical combination the nuclide exists.

The nitromethane- H on the other hand shows a variable counting yield since it is partly decomposed in the preceding separation in the gas chromatographic column.

The manner in which the method of the invention operates may be explained as follows: By means of the nickel catalyst a hydrogenating cracking of the higher-molecular compounds into simpler volatile compounds is effected. In this manner condensation is avoided. The cracking of aromatic compounds also avoids pseudo-activity easily caused by radioactive B-rays. Other disturbing components such as halogens, oxygen and sulphur are bound by reaction with the zinc as zinc halide, zinc oxide and zinc sulphide, respectively. Since the reactions do not take place in the presence of water, but rather in the gas stream which is preferably a mixture of hydrogen and methane the described memory effects" are avoided.

The invention permits a continuous measurement in a continuous gas flow and is therefore particularly suited for radio-gas chromatography. In such application, hydrogen may be utilized advantageously as the carrier gas. Methane will be added before the gas enters the reaction vessel. The methane is etfective in causing a more rapid flushing of the reaction vessel in which the catalyst is located as well as the counting tube and ensures that there can be no gas discharge in the counting tube (detector).

It is advantageous to use a catalyst of finely divided zinc and nickel on a support. The support at least partly prevents sintering of the catalyst upon melting of the zinc so that the flow resistance is not seriously increased thereby. It has been shown to be preferable if the temperature of the catalyst in direction of flow increases from about 662 F. (350 C.) to about 1148 F. (620" C.) anal then decreases again down to about 662 F. (350 C.

A further advantage results if the substances are additionally passed across a silver catalyst, preferably silver wool. The silver wool is preferably arranged in a relatively cool zone immediately downstream from the zincnickel-catalyst.

The silver catalyst serves the purpose of binding halogen hydrides which may form from the zinc halides and which condense from the high utilized temperatures in the cooler zones. Silver halides are not volatile and therefore cannot pass into the radioactivity detector.

An embodiment of the invention is schematically illustrated in the sole figure of the drawing and described as follows.

A gas chromatographic separating column is referenced 10 through which a hydrogen stream is passed as carrier gas, originating from tube 12. At the entrance of the separating column 10 a sample injector 14 is provided, at

the exit of which there is arranged a conventional thermal j conductivity detector 16, to the (lower) comparison or reference cell of which pure carrier gas H is supplied through line 18. The detector signal is recorded by means of a recorder 20. This is the customary arrangement of a gas chromatograph.

However, the gas emerging from the (upper) measuring 1 measuring the radioactivity which is generally referenced 22. This comprises a reaction vessel 24 in a furnace 26 and a counting tube 28 arranged therebehind. In front of the reaction vessel 24 methane is added through a line 30.

The reaction vessel 24 is preferably in the form of a U-tube, containing a zinc-nickel-catalyst 32. Between the zinc-nickel-contact plugs 34 of silver wool are provided at intervals. Such plugs also close off the ends of the U-tube protruding from the furnace and thus also maintain the zinc-nickel-catalyst in the tube mechanically.

The catalyst is produced for instance by mixing 70 parts of a mixture of zinc and nickel oxide (121.5) with 15 parts of support (firebrick). This mixture is heated together with the silver wool at about 662 F. (350 C.) in the hydrogen stream until no more water is produced. When this occurs, the nickel oxide has been reduced to nickel.

During use, the temperature of the catalyst will be about 350 C. at the two ends of the U-tube, but the temperature at the center of the tube will be about 620 C as previously noted. As generally described earlier, the compounds will be carried by the mixture of hydrogen (the original gas chromatograph carrier gas) and methane (introduced at 30, as already noted) through the U-tube, where the previously described catalytic reactions occur. The counting tube 28 thus measures the radioactivity of these reaction products, thereby eliminating problems of condensation, quenching, pseudo-radioactivity, and memory effects, as noted earlier. Conventional signal processing and recording may be utilized for the output of the radioactivity counting tube 28, as schematically illustrated in the drawing.

After some time the catalyzer will be exhausted, for instance, because the greater part of the zinc has become chemically bound. This becomes noticeable by an increase in the noise level or by the occurrence of pseudoactivities. Then, the contact may be regenerated by passing hydrogen therethrough for several hours.

A device of the type herein described for radio-gas chromatography may be utilized for many kinds of analyses, in particular in biochemistry, in organic chemistry and radiation chemistry for the clarification of reaction mechanisms, for the examination as to radiochemical purity, and the like. A few examples of such applications are described as follows.

(1) For clarifying the formation mechanism of butyric acid and other products in the so-called butyric acid fermentation it is of interest to run the conversion reaction in H-marked water. From the radioactivity of the water, and the formed hydrogen of the butyric acid and the acetic acid, conclusions are possible as to the reaction pattern occurring. As it is of particular interest to compare different substrates, the radio-gas chromatography is an ideal means of analyzing the products quickly and in a comparable manner.

(2) In the synthesis of (radioactivity) marked compounds extreme radiochemical purity is often important. Thus, for instance, the radiochemical purity of C-marked alkyl halides, required for the measurement of isotope effects, were examined with the aid of radio-gas chromatography.

(3) In the so-called direct marking of organic compounds with tritium gas extraordinarily complex substance mixtures were produced, which are characterized in that a high percentage of the radioactivity is present in unweighable quantities. For detecting and identifying these substances, radio-gas chromatography may be applied in the form of the present invention. Thus, the formation of methanol- H, ethanol- H, propanol- H, and isopropanol- H from propane-1,2 diol was determined.

The invention provides a method and device which permit the radio-gas chromatographic analysis of practically any desired substances. The inventive apparatus operates continuously and is therefore most favorably adapted to the mode of operation of gas chromatography. The invention requires a relatively short analysis time and relatively small amount of apparatus. Because of the invention many analyses with *C- and H-marked compounds become practicable for the first time.

What I claim is:

1. A method for measuring the radioactivity of a mixture of organic compounds, at least some of which are radioactively marked with at least one of C and H, comprising:

passing a continuous gas stream of said organic compounds in a carrier gas at a temperature of at least about 350 C. across a catalyst comprising zinc and nickel;

and then passing the resulting reaction products to a radioactivity detector, in which the radioactivity of said reaction products, and therefore of the original organic compounds, are measured;

said catalytic zinc and nickel reaction causing substantial conversion in the original organic compound mixture and therefore elimination of: the higher molecular weight compounds which might condense in the radioactive detector; the aromatic compounds which might cause pseudo-radioactivity measurement; and organic compounds containing halogens, oxygen and sulfur, which might cause capture of beta particles and therefore quenching of the radioactivity desired to 'be measured.

2. A method according to claim 1, in which:

a counting tube is used as the radioactivity detector;

and the carrier gas comprises a mixture of hydrogen and methane.

3. A method according to claim 1, in which:

said zinc and nickel catalyst comprise a mixture of finely divided zinc and nickel powder.

4. A method according to claim 1, in which:

the temperature at said zinc and nickel catalyst is maintained at about 350 C. at its two extremes and increases to about 620 C. near its central zone.

5. A method according to claim 1, in which:

the original organic compounds are passed through the separating column of a gas chromatograph prior to their being passed across said zinc and nickel catalyst.

6. A method according to claim 1, in which:

said continuous gas stream is additionally passed across a second catalyst of silver;

whereby any volatile halides are removed prior to passage into the radioactivity detector.

7. A method according to claim 6, in which:

said silver catalyst is in the form of a silver wool, at

least some of which is positioned in a relatively cool zone immediately downstream of said zinc and nickel catalyst.

8. Apparatus for measuring the radioactivity of a mixture of organic compounds, at least some of which are radioactively marked with at least one of C and H, comprising:

a flow-through reaction vessel containing a catalytic mixture of zinc and nickel;

means for supplying a continuous gas stream of said organic compounds in a carrier gas into the inlet of said reaction vessel;

a flow-through radioactivity detector;

and means connecting the outlet of said reaction vessel to said radioactivity detector;

whereby said catalytic zinc and nickel cause conversion and therefore substantial elimination from the original organic compound mixture of: the higher molecular weight compounds which might condense in the radioactivity detector; the aromatic compounds which might cause pseudo-radioactivity measurement; and organic compounds containing halogens, oxygen, and sulfur, which might cause capture of beta particles and therefore quenching of the radioactivity desired to be measured.

3,506,402 7 8 9. Apparatus according to claim 8, in which: References Cited said reaction vessel is enclosed within a temperature UNITED STATES PATENTS controlled oven.

10. Apparatus according to claim 8, in which: [1,122,003 12/1914 Humphrey's 2%113 said radioactivity detector comprises a counting tube. 2,905,536 9/ 1959 Emmett et a1.

11. Apparatus according to claim 8, in which: 5 2967,82? 1/1961 Langenbeck et 252473 said flow-through reaction vessel comprises a generally OTHER REFERENCES elongated tube; said zinc and nickel catalytic mixture comprises finely divided zinc and nickel powder on a support; 10 and each end of said elongated reaction tube contains a plug of silver wool. 12. Apparatus according to claim 11, in which: said elongated reaction tube contains additional silver Wolfgang, R., and Rowland, F. 5., Anal. Chem, 30, 9036 (1958).

Ormerod, E. C., and Scott, R. P. W., I. Chromatography, 2, 65-68 (1959).

MORRIS O. WOLK, Primary Examiner wool plugs in addition to those at each end; 15 REESE, Assistant Examiner whereby alternating zones of zinc and nickel catalyst and of silver wool are formed. 13. Apparatus according to claim 11, in which: 23 232 255; 195 1 3 5; 250 3 said elongated reaction tube is generally U-shaped;

and said U-shaped tube is enclosed within a tempera- 20 ture controlled oven, with the legs of said tube protruding from said oven.

Images