U.S. patent application number 09/947312 was filed with the patent office on 2002-03-21 for method and apparatus for determination of carbon-halogen compounds and applications thereof.
This patent application is currently assigned to San Diego State University, California corporation. Invention is credited to Borgerding, C. Albert, Gorelik, Vladimir Semenovich, Sharts, Clay Marcus.
Application Number | 20020033944 09/947312 |
Document ID | / |
Family ID | 26783532 |
Filed Date | 2002-03-21 |
United States Patent
Application |
20020033944 |
Kind Code |
A1 |
Sharts, Clay Marcus ; et
al. |
March 21, 2002 |
Method and apparatus for determination of carbon-halogen compounds
and applications thereof
Abstract
A method and apparatus for determination of fluoroorganic
compounds in liquid, gaseous, or crystalline or amorphous solids is
based on the detection of carbon-halogen bonds by laser Raman
spectroscopy. The method and apparatus provide a general method for
detecting and determination of halooorganic compounds. The method
and apparatus are applicable in the pharmaceutical industry, in
fluorinated drug research and manufacturing; in the medical and
clinical studies of the effects of fluoroorganic compounds; in the
environmental and agricultural studies and screening, in the
analysis of water, soils and air contaminated with fluoroorganic
compounds.
Inventors: |
Sharts, Clay Marcus; (San
Diego, CA) ; Gorelik, Vladimir Semenovich; (Moscow,
RU) ; Borgerding, C. Albert; (San Diego, CA) |
Correspondence
Address: |
SHEKHAR VYAS
Fish & Richardson P.C.
Suite 500
4350 La Jolla Village Drive
San Diego
CA
92122
US
|
Assignee: |
San Diego State University,
California corporation
|
Family ID: |
26783532 |
Appl. No.: |
09/947312 |
Filed: |
September 5, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09947312 |
Sep 5, 2001 |
|
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09343148 |
Jun 29, 1999 |
|
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6307625 |
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60091090 |
Jun 29, 1998 |
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60138643 |
Jun 10, 1999 |
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Current U.S.
Class: |
356/301 |
Current CPC
Class: |
G01N 2021/651 20130101;
G01N 21/65 20130101; G01N 21/658 20130101; G01J 3/44 20130101 |
Class at
Publication: |
356/301 |
International
Class: |
G01J 003/44; G01N
021/65 |
Claims
What is claimed is:
1. A method, comprising: providing a sample having a compound
including at least one carbon-halogen bond; and applying a
non-continuous light source to detect the carbon halogen bond.
2. The method of claim 1, wherein the applying the non-continuous
light source further comprises exposing the sample to a pulsed
metal-vapor laser.
3. The method of claim 1, wherein the at least one carbon-halogen
bond comprises at least one carbon-fluorine bond.
4. The method of claim 1, wherein the compound comprises one of
Prozac, Prozac substitutes, and Prozac metabolites.
5. The method of claim 1, wherein the compound comprises one of
5-Fluorouracil, 5-Fluorouracil drug substitutes, and 5-Fluorouracil
metabolites.
6. The method of claim 1, wherein the compound comprises one of
perfluorocarbons and substituted perfluorocarbons.
7. The method of claim 1, wherein the compound comprises
fluoropolymer bonds.
8. The method of claim 3 wherein applying a non-continuous light
source further comprises applying a metal vapor laser to detect the
at least one carbon-fluoride bond.
9. The method of claim 1, wherein the applying the non-continuous
light source comprises detecting characteristic Raman scattered
light that is indicative the carbon-halogen bond.
10. The method of claim 1, wherein the non-continuous light source
is one of a gold-vapor laser, copper-vapor laser, solid-state
laser, and a light bulb.
11. The method of claim 9, wherein the Raman scattered light
comprises at least one wave number between approximately 500
cm.sup.-1 to approximately 800 cm.sup.-1.
12. The method of claim 9, wherein the applying the non-continuous
light source comprises detecting Raman scattered light using a
pulse recording system.
13. The method of claim 1, wherein the providing the sample further
comprises providing the sample having the compound at approximately
10 to approximately 10.sup.6 grams/Liter.
14. The method of claim 1, wherein the at least one carbon-halogen
bond comprises at least one carbon-fluorine bond and the applying
the non-continuous light source comprises detecting a fully
symmetric vibrational normal mode of the at least one
carbon-fluorine bond.
15. The method of claim 1, wherein the at least one carbon-halogen
bond comprises at least one carbon-fluorine bond and the at least
one carbon-fluorine bond comprises one of at least one
trifluoromethyl group, at least one monofluoromethyl group, at
least one difluromethylene group, and at least one fluorinated
amino acid.
16. The method of claim 1, wherein the non-continuous light source
further comprises a wavelength that induces Raman scattered light
emissions from the at least one carbon-halogen bond.
17. The method of claim 16, wherein the wavelength is one of
approximately 510.6 nm, approximately 578.2 nm, and approximately
627.8 nm.
18. The method of claim 1, wherein the applying the non-continuous
light source further comprises time-gating the non-continuous light
source.
19. A method, comprising: providing at least one fluororganic
compound; applying a light source to the at least one fluororganic
compound determining at least one Raman frequency of an acoustic
mode of the at least one fluororganic compound; determining at
least one Raman frequency of an optical mode of the at least
fluororganic one compound; and determining a presence of the at
least one fluororganic compound as a function of one of the at
least one Raman frequency of the acoustic mode and the at least one
Raman frequency of the optical mode.
20. The method of claim 19, wherein the determining the presence
further comprises determining one of a concentration and a
molecular length of the at least one fluororganic compound.
21. The method of claim 19, wherein the excitation light source is
a metal-vapor laser.
22. The method of claim 19, wherein the at the at least one
fluoroorganic compound is one of quasi-linear and
quasi-one-dimensional.
23. The method of claim 19, wherein the at least one fluoroorganic
compound comprises a substitution group.
24. The method of claim 19, wherein the frequency of the acoustic
mode decreases with an increase of carbons in the at least one
fluoroorganic compound.
25. The method of claim 19, wherein the frequency of the optical
mode increases with a decrease of carbons in the at least one
fluoroorganic compound.
26. The method of claim 19, wherein the light source comprises a
non-continuous light source.
27. The method of claim 19, wherein the light source comprises one
of a gold-vapor laser, copper-vapor laser, solid-state laser, and a
light bulb.
28. A method, comprising: causing a sample to emit Raman scattered
light; detecting Raman scattered light indicative of a compound
having at least one carbon-halogen bond; and identifying the
compound in the sample.
29. The method of claim 28, wherein the at least one carbon-halogen
bond comprises at least one carbon-fluorine bond.
30. The method of claim 28, wherein the causing the sample further
comprises exposing the sample to a non-continuous light source.
31. The method of claim 28, wherein the light source comprises one
of a metal-vapor laser, gold-vapor laser, copper-vapor laser,
solid-state laser, and a light bulb.
32. The method of claim 30, wherein the causing the sample further
comprises time-gating the non-continuous light source.
33. A method, comprising: detecting at least one carbon-fluorine
bond in one of a drug, a biologically active compound, and a
biologically active substance; introducing the one of the drug, the
biologically active compound, and the biologically active substance
to a biological media; and determining at least one Raman frequency
emitted from one of the drug, the biologically active compound, and
the biologically active substance through the biological media.
34. The method of claim 33, wherein the determining the at least
one Raman frequency further comprises exposing a sample of the
biological media to an excitation light source to determine the at
least one Raman frequency.
35. The method of claim 34, wherein the determining the at least
one Raman frequency further comprises irradiating the sample with a
non-continuous light source.
36. The method of claim 34, wherein the light source is one of a
metal-vapor laser, gold-vapor laser, copper-vapor laser,
solid-state laser, and a light bulb.
37. The method of claim 33, wherein the drug comprises one of
Prozac, Prozac drug substitutes, and Prozac metabolites.
38. The method of claim 33, wherein the drug comprises one of
5-Fluorouracil, Fluorouracil drug substitutes, and Fluorouracil
metabolites.
39. The method of claim 33, wherein the drug comprises one of
perfluorocarbons and substituted perfluorocarbons.
40. A method, comprising: detecting at least one carbon-fluorine
bond in a blood substitute; introducing the blood substitute to a
biological media; and determining at least one Raman frequency
emitted from the blood substitute through the biological media.
41. The method of claim 40, wherein the determining the at least
one Raman frequency further comprises exposing a sample of the
biological media to an excitation light source to determine the at
least one Raman frequency.
42. The method of claim 41, wherein the exposing the sample further
comprises irradiating the sample with a non-continuous light
source.
43. The method of claim 41, wherein the light source is one of a
metal-vapor laser, gold-vapor laser, copper-vapor laser,
solid-state laser, and a light bulb.
44. A method, comprising: introducing at least one carbon-fluorine
bond to one of a compound and a substance; detecting the least one
carbon-fluorine bond; and using the at least one carbon-fluorine
bond as a tracer.
45. The method of claim 44, wherein the detecting of the at least
one carbon-fluorine bond comprises: exposing one of the substance
and the compound to an excitation light source having a wavelength
that induces Raman scattered light emission from the
carbon-fluorine bond; and detecting Raman scattered light emitted
from one of the substance and the compound.
46. The method of claim 44, wherein the exposing the sample further
comprises irradiating the sample with a non-continuous light
source.
47. The method of claim 45, wherein the light source is one of a
metal-vapor laser, gold-vapor laser, copper-vapor laser,
solid-state laser, and a light bulb.
48. A method, comprising: detecting at least one carbon-fluorine
bond in a sample; using the at least one carbon-fluorine bond in
the sample as a label; determining at least one concentration level
for one of water, soil, and air samples using the label.
49. The method of claim 48, wherein the detecting the at least one
carbon-fluorine bond comprises: exposing the sample to an
excitation light source having a wavelength that induces Raman
scatter light emission from the at least one carbon-fluorine bond;
and detecting Raman scattered light emitted from the sample,
wherein detection of characteristic Raman scattered light is
indicative of the at least one carbon-fluorine bond in the
sample.
50. The method of claim 49, wherein the exposing the sample further
comprises irradiating the sample with a non-continuous light
source.
51. The method of claim 49, wherein the light source is one of a
metal-vapor laser, gold-vapor laser, copper-vapor laser,
solid-state laser, and a light bulb.
52. A method, comprising: introducing at least one carbon-fluorine
bond to a drug; detecting the least one carbon-fluorine bond in the
drug; and using the at least one carbon-fluorine bond as a
label.
53. The method of claim 52, wherein the determining the at least
one Raman frequency further comprises exposing a sample to an
excitation light source to determine the at least one Raman
frequency.
54. The method of claim 53, wherein exposing the sample further
comprises irradiating the sample with a non-continuous light
source.
55. The method of claim 53, wherein the light source is one of a
metal-vapor laser, gold-vapor laser, copper-vapor laser,
solid-state laser, and a light bulb.
56. A method, comprising: exposing a sample to a pulsed metal-vapor
laser having a wavelength that induces Raman scattered light
emission from at least one carbon-fluorine bond; time-gating the
pulsed metal-vapor laser; and detecting Raman scattered light
emitted from a compound in the sample, wherein detection of
characteristic Raman scattered light is indicative of at least one
carbon-fluorine bond of the compound.
57. The method of claim 56, wherein the metal-vapor laser is one of
a copper-vapor laser and a gold-vapor laser.
58. The method of claim 56, wherein the detecting of Raman
scattered light comprises detecting the Raman scattered light using
a photomultiplier.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of United States
Provisional Patent Application No. 60/091,090, filed Jun. 29, 1998;
United States Provisional Patent Application No. 60/138,643, filed
Jun. 10, 1999, and United States Patent Application No. 09/343,148,
filed Jun. 29, 1999.
TECHNICAL FIELD
[0002] This invention relates generally to measuring and testing by
dispersed light spectroscopy with Raman type light scattering, and
more particularly to Raman spectroscopy for the determination of
carbon-halogen and fluoroorganic compounds.
BACKGROUND
[0003] Qualitative and quantitative analysis of fluoroorganic
compounds is an important practical task. Fluoroorganic compounds
are widely used in the pharmaceutical industry. About one-third of
all newly patented drugs contain carbon-fluorine (C-F) bonds.
Examples of fluorine-containing drugs are the anticancer drug
Fluoracil (C.sub.4H.sub.3FN.sub.2O.sub.2, 5-fluorouracil),
antidepressant drug Prozac.RTM. (C.sub.17H.sub.18F.sub.3- NO,
fluoroxetine) and painkiller Dalmane (C.sub.21H.sub.23C1FN.sub.3O,
flurazepam). Perflubron (C.sub.8F.sub.17Br, bromoperfluorooctane)
is an oxygen-carrier in a formulation now undergoing clinical
trials as a blood substitute. Many agricultural chemicals and
pesticides also contain carbon-fluorine bonds.
[0004] Chemical analysis for drugs can be done by isolating the
drug and then measuring concentrations of compounds. This approach
can be expensive. Alternatively, known chemical compounds can be
labeled with radioactive elements to form tracers. The radioactive
compounds and their metabolites can be followed in the body or
tissues by observing emitted radioactivity. However, making and
disposing of radiolabeled compounds is also expensive. These
expenses can be found in many drug development programs.
[0005] Accordingly, the inventors have determined that it would be
useful to accurately and inexpensively identify fluoroorganic
compounds. The present invention provides a method and apparatus
for achieving this object.
SUMMARY OF THE INVENTION
[0006] The invention is directed to an apparatus and method for
detecting the presence of compounds having carbon-halogen bonds
using Raman spectroscopy. The method detects any carbon-halogen
bond, and is particularly useful in detecting carbon-fluorine
bonds.
[0007] In one aspect, the method uses pulsed laser Raman
spectroscopy to detect carbon-halogen bonds, using an effect of
inelastic scattering of light. A sample is irradiated from a
noncontinuous periodic pulse light source, such as a metal-vapor
laser. Raman scattered light emitted from the sample is then
detected to determine if a characteristic Raman scattered light
spectrum for a compound having a carbon-halogen is present in the
sample.
[0008] In another aspect, the apparatus for Raman spectroscopy
includes a noncontinuous periodic pulse metal vapor laser and a
monochromator for visible and ultraviolet light. The apparatus also
includes a detector for detecting the emitted Raman scattered light
and a pulse recording system to eliminate primary fluorescence
associated with the sample.
[0009] In yet another aspect, the invention is directed to a method
for detecting a fluoroorganic compound that includes exposing a
sample to an excitation light source and measuring a frequency of
an acoustic mode of the compound. The method also includes
measuring a frequency of an optical mode of the compound and
detecting a shift in the optical and acoustic mode frequencies. The
molecular length of the compound is approximated as a function of
the shift in frequencies to determine the presence of the
fluoroorganic compound.
[0010] The details of one or more embodiments of the invention are
set forth in the accompanying drawings and the description below.
Other features, objects, and advantages of the invention will be
apparent from the description and drawings, and from the
claims.
DESCRIPTION OF DRAWINGS
[0011] FIG. 1 is a schematic drawing of a Raman spectrometer in
accordance with a preferred embodiment.
[0012] FIG. 2 is a Raman spectrum of C.sub.8H.sub.17Br
(bromoperfluorooctane) and C.sub.8H.sub.18 using the spectrometer
of FIG. 1.
[0013] FIG. 3 is a Raman spectrum of C.sub.9F.sub.19COOH
(C.sub.10HF.sub.19O.sub.2; bromoperfluordecanoic acid).
C.sub.9H.sub.20 (nonane, a hydrocarbon) using the spectrometer of
FIG. 1.
[0014] FIG. 4 is a Raman spectrum of
C.sub.6H.sub.3(CF.sub.3).sub.3[1,3,5--
tris(trisfluoromethyl)benzene] and C.sub.6H.sub.6 (benzene) using
the spectrometer of FIG. 1.
[0015] FIG. 5 is a Raman spectrum of a commercial preparation of
fluoxetine hydrochloride using the spectrometer of FIG. 1.
[0016] FIG. 6 is a schematic drawing of a resonance Raman
spectrometer in accordance with a preferred embodiment.
[0017] FIG. 7 is a resonance Raman spectrum of irradiate
perfluorodecalin showing a difluoromethylene absorption. The top
spectrum is an unprocessed resonance Raman spectrum of
perfluorodecalin (C.sub.10F.sub.18). The bottom spectrum is a
partially processed resonance Raman spectrum of
perfluorodecalin.
[0018] FIG. 8 is a resonance Raman spectrum of
1-bromoperfluorooctane using the spectrometer of FIG. 6.
[0019] FIG. 9 shows structures of some commercially useful
fluoroorganic compounds.
[0020] FIG. 10 shows structures of various compounds having Raman
spectra.
[0021] FIG. 11 illustrates Raman spectra of C.sub.nF.sub.2n+1Br for
n=6, 7, 8, 9, 10, 14 in the region 0-1500 cm.sup.-1.
[0022] FIG. 12 illustrates the dependency of Raman spectra on the
unit length of a molecule in the lower frequency region LAM.
[0023] FIG. 13 illustrates the dependency of Raman spectra on the
unit length of a molecule in the higher frequency region LOM.
[0024] FIG. 14 illustrates experimental Raman frequencies.
[0025] FIG. 15 illustrates the Raman spectra of a two-component
mixture of C.sub.nF.sub.2n+1Br obtained at three concentrations of
components at a Raman signal for a CF.sub.2 bond.
[0026] FIG. 16 illustrates the Raman spectra of a two-component
mixture of C.sub.nF.sub.2n+1Br obtained at three different
concentrations of the components at a characteristic Raman signal
in the lower frequency region LAM band.
[0027] Like reference numbers and designations in the various
drawings indicate like elements.
DETAILED DESCRIPTION
[0028] In general, the invention is directed to a method and an
apparatus for determining the presence, in a sample, of compounds
having carbon-halogen bonds and, in particular, carbon-fluorine
bonds. The method uses pulsed laser Raman spectroscopy to detect
carbon-halogen bonds, using an effect of inelastic scattering of
light. The apparatus includes a metal-vapor laser source and a
pulse recording system, to permit the recording of Raman signals
for carbon-halogen bonds.
[0029] The invention is based on a principle different from most
organic chemistry analyses, i.e., analysis by bond rather than
analysis by compound. The method of the invention does not identify
a compound; rather the presence of a carbon-halogen bond is
determined, using the carbon-halogen bond as a chemical tracer. In
particular, the method detects all types of carbon-fluorine
bonds.
[0030] The method is useful for analysis of fluoroorganic compounds
at 10.sup.-3-10.sup.-6 g/L (ppm-ppb level) for pharmaceutical,
biological, medical and biomedical applications, and for
environmental analysis of water, soils and air contaminated with
such compounds. Full development of resonance Raman technology may
lead to detection at better than parts per billion levels. The
invention usefully reduces the operational costs for analysis of
fluoroorganic compounds (being less expensive than current methods
based on extraction and compound isolation, with identification by
chromatography or mass spectrometry), and makes such analysis more
rapid.
[0031] The apparatus of the invention has several advantages for
the observation of the Raman spectra of fluoroorganic compound. A
periodic pulse vapor-metal laser source, such as copper-vapor or
gold-vapor lasers, is used for sample excitation. Metal-vapor
lasers are characterized by an ability to produce short and
powerful pulses in the visible and ultraviolet region. These lasers
are able to produce pulses of light with high peak and average
operating power with air cooling.
[0032] Analysis for a carbon-fluorine bond rather than for a
fluoroorganic compound specifically is possible because organic
fluorine compounds with a carbon-fluorine bond are rarely not found
in nature. Except for a few rare exceptional compounds found in a
few plants or microorganisms (e.g., sodium fluoroacetate and
fluorooleic acid, both found in certain plants in Africa),
carbon-fluorine bonds generally do not exist in natural products
(Key et al., Environmental Science and Technology 31:2445-2454,
1997). Consequently, finding a carbon-fluorine bond in any system
means an artificial compound exists in the sample. Additionally,
all known biologically produced fluorinated organic molecules
contain only one fluorine atom. If a fluorinated compound is found
in or found on biologically derived animal or vegetable material,
the compound is almost certainly artificial, not natural. If a
fluorinated compound is injected or ingested by a vegetable or
animal biological material, any fluoroorganic compound found must
be the material injected or ingested or be a metabolite of the
material injected or ingested. The carbon-fluorine bond is strong
and generally cannot be modified biologically. This means that the
carbon-fluorine bond can be used as a tracer group because the bond
does not alter state when exposed to biological processes.
[0033] Unless otherwise defined, all technical and scientific terms
used herein have substantially the same meaning as commonly
understood by one of ordinary skill in the art to which this
invention belongs. Although many methods and materials similar or
equivalent to those described herein can be used in the practice or
testing of the present invention, suitable methods and materials
are described below.
[0034] All publications, patent applications, patents, and other
references mentioned herein are incorporated by reference in their
entirety. In case of conflict, the present application, including
definitions, will control. In addition, the materials, methods, and
examples described herein are illustrative only and not intended to
be limiting.
[0035] Other features and advantages of the invention will be
apparent from the following detailed description, the drawings, and
from the claims.
[0036] Raman Spectroscopy
[0037] An authoritative book (Wolverson, in An Introduction to
Laser Spectroscopy, Andrews & Demidov, Eds., Plenum Press, New
York, 1995, pp. 91-114) concisely defines Raman spectroscopy as
follows: "Raman spectroscopy is the inelastic scattering of light
by a material; the word `inelastic` implies that energy is
transferred between the light quanta and the material, so that the
scattered light may have a longer or shorter wavelength than the
incident light. The study of light scattered from a particular
material is therefore termed Raman spectroscopy and is of interest
because, as will be seen, information can be gained about the
structure, the composition, and the vibrational or electronic
states of the scattered material. Raman spectroscopy is a large
field, with many variations on the basic technique and with many
new applications being found each year." An older, alternative
description of the Raman effect and Raman spectroscopy may be found
in other sources, e.g., Spectroscopy Source Book, Science Reference
Series, McGraw-Hill, New York, 1988, pp. 145-151.
[0038] The intensity of normal Raman peaks of the frequency of
incident light is described by Skoog & Leary (Principles of
Instrumental Analysis, 4.sup.th edition, Saunders Publishing,
Philadelphia, 1992, p. 301) as follows: "The intensity of power of
a normal Raman peak depends in a complex way upon the polarizabiliy
of the active group, as well as other factors. In the absence of
absorption, the power of the Raman emission increases the fourth
power of the frequency of the source; however, advantage can seldom
be taken of this relationship because of the likelihood that
ultraviolet radiation will cause photodecomposition. Raman
intensities are usually directly proportional to the concentration
of the active species. In this regard, Raman spectroscopy more
closely resembles fluorescence than absorption, where the
concentration-intensity relationship is logarithmic."
[0039] The teaching of the quoted authors bears importantly on the
use of pulsed metal-vapor lasers. Conventional Raman spectroscopy
using a continuous wave Nd:YAG laser does not have sufficient
energy in the incident light to cause fluorescence. Because the
intensity of the Raman signal is proportional to the fourth power
of the frequency of incident light, and therefore inversely
proportional to the fourth power of the wavelength of incident
light, the signal strength of the inelastically scattered light is
about 16 times greater at the wavelength of 510.6 nm (copper-vapor
laser) than at the conventionally used wavelength of 1064 nm
(Nd:YAG laser). Other lasers operating with higher energy
continuous wave light (such as argon at 488.8 and 514.5 nm, krypton
at 647.1 nm, and helium-neon at 632.8 nm) cause photodecomposition
of samples, as described by Skoog & Leary, above. When any
compound in a sample mixture gives primary fluorescence, then
observation of Raman spectra of the sample is severely limited. In
contrast, by using a pulsed laser at about 10,000 Hertz and a very
short pulse width of about 12 nanoseconds, samples do not undergo
the photodecomposition discussed by Skoog & Leary, above. Using
a pulsed copper-vapor laser permits elimination of inherent
fluorescence by using a timing-gate for the detector. The invention
thus uses higher energy incident light to give a much stronger
signal.
[0040] Apparatus
[0041] The Pulsed Laser Raman Spectroscopy of the invention is
achieved using non-continuous periodic pulse vapor metal laser
sources and by using a stroboscopic pulse recording system.
Suitable lasers include copper-vapor or gold-vapor lasers.
Alternatively, any pulsing light source such as a solid state light
source or a light bulb can be used. The apparatus can be a
modification of copper-vapor and gold-vapor lasers that have been
used to provide energy for two-photon excitation of a compound.
(Gorelik et al., Journal of Molecular Structure 266:121-126, 1992;
Gorelik & Kozulin, Quantum Electronics (Russia) 21:499-501,
1994; Gorelik & Zhabotinskii, Quantum Electronics (Russia)
24:273-275, 1994). In Gorelik's two-photon excitation studies,
exciting light was green (510.5 nm) or yellow (578.2 nm) from the
copper-vapor laser or red (627.8 nm) from the gold-vapor laser. The
goal of these studies was the production of primary fluorescence in
the ultraviolet and blue ranges of the spectra. The above studies
did not contemplate Raman spectroscopy of the carbon-fluorine bond.
For Raman spectroscopy, efforts are made to eliminate primary
fluorescence and to collect only the inelastically scattered Raman
light. For resonance Raman spectroscopy, a frequency doubling
crystal is required.
[0042] Metal-vapor lasers are air cooled or water cooled and
consume only about 1-2 kW of electrical power. These lasers may
have a coefficient of efficiency of about 1%. The air-cooled
copper-vapor laser operates at an average power of about 1-10
watts. This means that metal vapor lasers operate more efficiently
and cost less to operate than many other laboratory lasers. Thus,
the laser can be combined with other commercial components to
produce an inexpensive Raman instrument for obtaining Raman spectra
of fluoroorganic compounds. A Raman instrument can be designed for
spectral range of about 550-900 cm.sup.-1. The instrument can also
be designed for a range of about 500-1500 cm.sup.-1. In this case,
the instrument may be capable of presenting detection in the normal
1000-1400 cm.sup.-1 vibrational range of the carbon-fluorine
bond.
[0043] FIG. 1 illustrates a Raman instrument 100 that includes a
metal-vapor laser. Suitable lasers include a copper-vapor or a
gold-vapor laser. The Raman instrument 100 also includes a mirror
102 with dielectric and highly reflective coating to efficiently
reflect a generated laser radiation, and a photodiode 103 for
collecting a laser radiation. The instrument 100 also includes an
electronic unit 104 (e.g., a stroboscopic generator) and a
condensing lens 105 that focuses a laser beam on the sample 106 to
be analyzed (the sample 106 not being a component of the
apparatus). Condensing lenses 107 and 108 are used to focus beams
on the spectrometer slit after passing through the sample 106 and
an absorbance filter 109 is used to pass a Raman emission signal
(secondary radiation). The Raman instrument 100 also includes a
single or double monochromator spectrometer 110, a detector of
secondary radiation 111 (e.g., a photomultiplier), a pulse
recording system 112 controlled by the stroboscopic system 104,
and, optionally, a computer 113 for data collection and processing
and for management of the spectrometer 110. The spectrophotometer
110 may be a single, double, or triple monochomator for the visible
and ultraviolet region of the spectra, equipped with a
photomultiplier 111 and sensitive photon-counting detector system
112. The high energy laser 101 pulses irradiate the fluoroorganic
sample 106 and also activate a device 104, to form a strobe-impulse
used to synchronize the pulse recording system 112. Samples
preferably are placed into cylindrical quartz cuvettes having
parallel windows (not shown). Raman spectra is observed at
90.degree. with respect to the incident pulse by using a single or
double monochromator 110 with a single channel detection. When
irradiated, the sample 106 emits pulsed Raman radiation and also
scatters part of the incident Raman pulse. The absorbance filter
109 removes scattered radiation and passes the pulsed Raman
radiation to the spectrometer 110. Signals are photomultiplied and
sent to a synchronized pulse recording system 112. To obtain
ultraviolet radiation (255.3 nm; 271.2 nm and 289.1 nm), a doubling
crystal, such as BaB.sub.2O.sub.4, or a tripling crystal, can be
used.
[0044] A suitable laser 101 that can be used with the apparatus is
designed and manufactured at Lebedev Institute of Physics (Russian
Academy of Sciences, Moscow, Russia). One such laser is a 3-watt or
10-watt Russian-designed air-cooled copper-vapor laser manufactured
by the Lebedev Physics Institute. A stroboscopic generator 104 that
can be used with the instrument 100 is also designed and
manufactured at Lebedev Institute of Physics (Russian Academy of
Sciences, Moscow, Russia). The spectrophotometer 110 can be any
standard monochomator or a commercial product such as a Jobin-Yvon
U1000 double monochromator Raman spectrometer. Preferably, this
spectrophotometer is modified to permit observation of the spectra
of fluoroorganic compounds as shown in FIGS. 2-8, below. The
optical filter can be a GUI-6 absorption optical filter. The
monochromator can be an MSD-2 monochromator. The photomultiplier
111 can be an FEU-106 photomultiplier.
[0045] Excitation light emitted by the metal-vapor laser 101 are
attenuated by an optical absorption filter 109 placed in front of a
sample 106. The filter 106 is used to limit the excitation light
going to the sample. In the spectral range 200-400 nm, the filter
109 can be an ultraviolet filter, such as a GUI-6. In the range
360-480 nm, the filter can be a blue wavelength filter, such as a
BG-12. GUI-6 and BG-12 filters are commercially available from
AGFA. The luminescence spectra are preferably normalized to allow
for the transmission coefficient of the relevant filter 109.
[0046] A pulsed metal-vapor laser 101 has significant advantages
over continuous wave argon or helium-neon lasers. The pulsed signal
generates significantly less photodecomposition and permits the
simple elimination of primary fluorescence, as described by Skoog
& Leary, above. Further, laser 101 is significantly cheaper
than Raman spectrometers that use longer wavelength excitation
lasers, particularly to the Nd:YAG laser at 1064 nm, to eliminate
fluorescence. This is because the longer wavelength lasers require
expensive CCD signal detectors that significantly increase
cost.
[0047] The metal-vapor laser 101 can provide about 16 times the
signal of commercial Nd:YAG laser Raman spectrometers. Because the
Raman vibrational scattering emissions are detected during a narrow
time internal ("gate") approximately equal to the laser pulse
duration (10.sup.-8 sec), fluorescence is eliminated. Pulsed
techniques also give enhanced sensitivity.
[0048] Thus, the intense characteristic Raman band of the symmetric
vibrational normal mode of carbon-fluorine bond or groups in the
Raman spectra of organic compounds, excited by the pulse laser
source, can be established. For example, to achieve optimal
excitation of a C-F band, the exposure of the sample to the
excitation source must be 10.sup.-8 seconds or more. Preferably,
the Raman spectrum is measured within the above exposure period.
Therefore, the Raman spectra is not affected by fluorescence.
[0049] The present inventors have discovered that, using the Raman
instrument 100, an emitting signal of a carbon-fluorine bond normal
mode (vibrational) or carbon-fluorine group normal mode
(rotational), which occurs within a narrow frequency range, is very
strong with recognizable narrow band widths. The term "normal mode"
refers to the symmetric vibrational process of excited atoms. The
radiation characteristic of carbon-fluorine bonds may be detected
in the 500-800 cm.sup.-1 region. Other radiation in the 950-1400
cm.sup.-1 region commonly associated with fluoroorganic compounds
can also be observed.
[0050] The published frequency range for carbon-fluorine bond
infrared absorption is 1000 cm.sup.-1 to 1400 cm.sup.-1 These other
bands are useful and can be used to confirm carbon-fluorine groups
detected by the method of the invention. However, these infrared
absorptions are subject to interference by other functional groups
in the fluoroorganic compound, as discussed above.
[0051] A type of carbon-fluorine bond can also be identified in the
preferred method. It is contemplated that the method of the
invention does not measure the vibration of fluorine against carbon
(such C-F vibrations occur in the infrared at 1000-1400 cm.sup.-1).
Rather, the method detects deviations from the totally symmetric
Raman active mode of the groups (such as the carbon-fluorine group
in the aromatic compound hexafluorobenzene or the trifluoromethyl
group in trifluoromethylated compounds, such as
1,3,5-tris(trisfluoromethyl)benzene). The method detects changes in
the polarization of carbon-fluorine groups as part of the total
molecular vibrational normal modes.
[0052] The laser 101 is adaptable to frequency doubling to give a
strong signal in the ultraviolet (UV) at about 255.4 nm. UV signals
at 272 nm and 289 nm are also available. Irradiation of samples in
the ultraviolet allows the observation of resonance Raman spectra
which have signals approximately 10.sup.4 to 10.sup.5 stronger
(10,000-100,000 times stronger) than normal Raman signals.
Resonance Raman signals means detection of compounds containing
carbon-fluorine bonds at the parts per billion (ppb) level.
Frequency doubling of the wavelengths is observed for both the
copper-vapor laser and the gold-vapor laser.
[0053] FIG. 6 is a schematic drawing of a Raman spectrometer 200 as
adapted for resonance Raman spectroscopy. The Raman spectrometer
200 is similar to the Raman instrument 100 in FIG. 1. However, the
spectrometer 200 includes a non-linear frequency doubling crystal
4. The frequency doubling crystal can be constructed of barium
borate. The spectrometer 200 may also include additional filters
14.
[0054] The doubled frequencies, expressed as wavelengths, for a
copper-vapor laser may be about 255 nm and 289 nm. A combination
band at 272 nm may also be useful. For a gold-vapor laser, the
doubled frequency wavelength is about 314 nm. Almost all of the
compounds of TABLE 1 below have aromatic rings and are almost
certain to give significant enhancement of the resonance Raman
emission signal due to the high self-absorbance of the aromatic
ring structures. Aromatic rings absorb energy at frequencies
similar to those emitted (self-absorption). Using a frequency
doubling crystal, the frequency may be shifted from 510.6 nm to
255.3 nm where it is absorbed.
[0055] The spectrometer 200 permits a significant suppression of
dark current and environmental noise, and also increases
sensitivity. The background of continuous fluorescence can be
suppressed by using a strobe-impulse. The strobe-impulse is
synchronized with a laser source pulse and "opens" a detection
system for only about 10.sup.-8 sec. This period corresponds to the
duration of the preferred laser pulse. As a result, the
spectrometer 200 permits a low level detection of fluoroorganic
compounds.
[0056] Compounds
[0057] A Raman band that is characteristic of carbon-fluorine bonds
can be found in the range 540 cm.sup.-1 to 785 cm.sup.-1, based on
experimental observations. For estimation purposes, a range of
500-800 cm.sup.-1 is reasonable.
[0058] Many fluoroorganic compounds are manufactured commercially.
Most of the compounds find use as drugs in medicine or veterinary
medicine, anesthetics, herbicides, insecticides, pesticides or as
industrial intermediates. FIG. 9 shows the structures of some
commercially useful compounds. These compounds include
carbon-fluorine bonds of trifluoromethyl groups, aromatic
carbon-fluorine bonds, and perfluoroalkyl groups.
[0059] Aromatic carbon-fluorine bonds are observed in the range of
540-610 cm.sup.-1. Examples are hexafluorobenzene, 569 cm.sup.-1;
and pentafluoropyridine, 589 cm.sup.-1.
[0060] Trifluoromethyl groups are observed in the range of 710-785
cm.sup.-1. Examples are: 1-bromoperfluorooctane, 726 cm.sup.-1;
perfluorodecanoic acid, 730 cm.sup.-1; triperfluoropropylamine, 750
cm.sup.-1; 1,3,5-tris-(trifluoromethylbenzene), 730 cm.sup.-1;
fluoxetine (Prozac.RTM.) commercial powdered pill at 770 cm.sup.-1.
TABLE 1 (see, Key et al., Environmental Science and Technology
31:2445-2454, 1997) lists commercial fluoroorganic compounds
containing trifluoromethyl groups. Most of these compounds have an
aromatic ring, so resonance Raman can be observed. For example,
Prozac.RTM. gives a sharp identifiable signal at 770 cm.sup.-1, as
shown in FIG. 5.
1TABLE 1 APPLICATIONS OF TRIFLUOROMETHYL-SUBSTITUTE- D ORGANIC
COMPOUNDS Herbicides Herbicides Insecticides Fungicide Medicinal
(Use) acifluorifen flurtamone acrinathrin fluazinam
bendroflumethiazide benfluralin fluxofenim bifenthrin flusulfamide
(antihypertensive) diflufenican fomesafen chlorfluazuron flutolanil
dexfenfluramine dinitramine furyloxyfen cyhalothrin furconazole
(obesity) dithiopyr haloxyfop flucofuron triflumizole fenfluramine
ethaifluralin lactofen flufenoxuron Anaesthetics (anorectic)
flazasulfuron mefluidide X-fluvalinate fluroxene fluoxetine
fluazifop nipyraclofen hydramethylnon halothane (antidepressant)
fluchioralin norflurazon tefluthrin methoxyflurane fluphenazine
flumetralin oxyfluorfen triflumuron isoflurane (antipsychotic)
fluometuron perfluidone Rodenticide sevoflurane halofantrine and
fluoroglycofen prodiamine bromethalin desfiurane mefloquine.HCl
flurazole profluralin flocoumafen Lamoricide (antimalarials)
flurochloridane thiazafluron flupropadine trifluoromethyl-
nilutamide (cancer) flurprimidol trifluralin nitrophenol tolrestat
(diabetes)
[0061] When no trifluoromethyl group is present, difluromethylene
groups are observed in a range centered at 690 cm.sup.-1. An
example is perfluorodecalin, a component of blood substitutes
developed in Japan and Russia.
[0062] In particular embodiments, Raman spectroscopy can be
performed on 1-bromoperfluorooctane (C.sub.8F.sub.17Br; BPFO),
polycrystalline perfluorodecanoic acid (C.sub.9F.sub.19COOH; PFDA),
1,3,5-tris-(trifluoromethyl)-benzene
(C.sub.6H.sub.3(CF.sub.3).sub.3; TTFMB); or fluoxetine
(Prozac.RTM.). The first compound (C.sub.8F.sub.17Br) is a
candidate to carry oxygen in a blood substitute. The second
compound (C.sub.8F.sub.17COOH) is an analog of perfluorooctanoic
acid (PFOA), but less volatile. PFOA has been found in tissues of
workers exposed to PFOA in the workplace. The third compound
(C.sub.6H.sub.3(CF.sub.3).sub.3) contains carbon-fluorine bonds
that are in trifluoromethyl groups. C.sub.6H.sub.3(CF.sub.3).sub.3
is an analog of many useful compounds now sold commercially as
drugs, herbicides, and pesticides, some of which are presented in
TABLE 1. Fluoxetine (Prozac.RTM.; C.sub.17H.sub.18F.sub.3NO) is a
widely prescribed drug which contains a trifluoromethyl group.
[0063] In further embodiments, resonance Raman spectroscopy can be
performed on perfluorodecalin (C.sub.8F.sub.18, PFD) and
1-bromoperfluorooctane (C.sub.8F.sub.17Br, BPFO). The schematic of
the instrument used to observe the resonance Raman spectra is given
in FIG. 6. Most of the compounds of TABLE 1 should give enhanced
resonance Raman spectra.
[0064] A Raman spectrum (0-1500 cm.sup.-1) of liquid
C.sub.8F.sub.17Br (BPFO) is shown in FIG. 2. A very strong peak at
730 cm.sup.-1 is present in this spectrum. The compound
C.sub.8F.sub.17Br is a fluoro-derivative of octane
(C.sub.8H.sub.18) in which the 18 hydrogens are replaced with 17
fluorine atoms and one atom of bromine. FIG. 2 also shows a Raman
spectrum of C.sub.8H.sub.18 in the upper right comer. This spectrum
does not have a peak near 730 cm.sup.-1. As in
C.sub.6H.sub.3(CF.sub.3).sub.3 spectrum, the appearance of the 730
cm.sup.-1 peak in C.sub.8F.sub.17Br is due to a carbon-fluorine
bond signature. This peak corresponds to a fully symmetric
vibrational normal mode of a molecule containing the
carbon-fluorine bond, specifically the trifluoromethyl group or
perfluoroalkyl group.
[0065] A Raman spectrum for polycrystalline C.sub.9F.sub.19COOH
(PFDA) is given in FIG. 3. As for earlier discussed fluoroorganic
compounds, a characteristic peak at 726 cm.sup.-1 has been observed
for C.sub.8F.sub.17COOH. This peak was assigned as a fully
symmetric vibrational normal mode of a molecule containing the C-F
bond, specifically the trifluoromethyl group or perfluoroalkyl
group. The Raman spectrum of nonane (C.sub.9H.sub.20) is shown in
the upper right comer in FIG. 3. The nonane spectrum does not have
any characteristic spectral lines close to 730 cm.sup.-1.
[0066] A Raman spectrum for C.sub.6H.sub.3(CF.sub.3).sub.3 (TTFMB)
and benzene (C.sub.6H.sub.6, upper right) are shown in FIG. 4. When
these two Raman spectra are compared, each has a well-resolved peak
at 992 cm.sup.-1, which corresponds to the fully symmetric
vibrational mode of the benzene ring. At wave numbers greater than
992 cm.sup.-1 the Raman spectrum of C.sub.6H.sub.3(CF.sub.3).sub.3
shows a doublet at 1085.sup.-1, 125 cm.sup.-1 and spectral lines at
1376 cm.sup.-1, 1513 cm.sup.-1, and 1637 cm.sup.-1 instead of the
single lines at 1178 cm.sup.-1 and 1586 cm.sup.-1 found for carbon
in benzene. The difference between C.sub.6H.sub.3(CF.sub.3).sub.3
and unsubstituted benzene becomes apparent below 992 cm.sup.-1.
Benzene shows only two weak peaks which correspond to the
deformation modes of the C-C bond. By contrast,
C.sub.6H.sub.3(CF.sub.3).sub.3 shows a strong peak at 730 cm.sup.-1
comparable in intensity to the peaks in
C.sub.6H.sub.3(CF.sub.3).sub.3 and C.sub.6H.sub.6 at 992 cm.sup.-1.
The 730 cm.sup.-1 peak is assigned as a fully symmetric vibrational
normal mode of the trifluoromethyl group of the molecule.
[0067] The Raman spectrum in FIG. 5 is of the contents of a
fluoroxetine (C.sub.17H.sub.18F.sub.3NO) hydrochloride
(Prozac.RTM.) capsule in the solid powdered form. The composition
of the capsule is unknown other than the presence of fluoroxetine
hydrochloride. The very narrow sharp peak at 770 cm.sup.-1 is
assigned to a symmetrical vibration involving the trifluoromethyl
group. The symmetric aromatic vibration is found at 1001
cm.sup.-1.
[0068] The Raman spectra of each of the four fluoroorganic
compounds (C.sub.8F.sub.17Br, C.sub.8F.sub.17COOH,
C.sub.6H.sub.3(CF.sub.3).sub.3, and C.sub.17H.sub.18F.sub.3NO) show
a characteristic fully symmetric vibrational strong peak at
frequencies in the range of 720-770 cm.sup.-1 which are assigned to
molecular vibrations of the trifluoromethyl group or perfluoroalkyl
groups. Comparison of the Raman spectra of the fluoroorganic
compounds with their hydrocarbon analogs, suggest that the observed
spectral emissions in the range of 690-770 cm.sup.-1 are associated
with the carbon-fluorine bonds of the compounds studied.
[0069] Resonance Raman spectra of perfluorodecalin
(C.sub.8F.sub.18) and 1-bromofluorooctane (C.sub.8F.sub.17Br) are
shown in FIG. 7 and FIG. 8. These spectra are shown at two
different scales, but are not otherwise electronically processed to
enhance the signals. The narrow sharp emission at 692 cm.sup.-1 is
believed to be the totally symmetric normal mode of the
difluoromethylene groups (CF.sub.2). 1-bromoperfluorooctane has a
weak ultraviolet absorption maximum about 275 nm (.epsilon.=50) and
gives a resonance Raman spectrum with a 730 cm.sup.-1 emission
signal, which is the same emission shown in the regular Raman
spectrum (FIG. 2).
[0070] Quasi-one-dimensional molecules
[0071] As described above, the preferred method detects compounds
having carbon-fluorine bonds. It has also been found that carbons
in the "quasi-linear" or "quasi-one-dimensional" fluororganic
molecule chain having a formula C.sub.nH.sub.2n+2 e.g.,
C.sub.nF.sub.2n+1 can also be identified. These molecules are often
used in drug formulations, which transport oxygen or carbon dioxide
in blood substitutes. These molecules are also used in other
pharmaceutical and medicinal applications. Examples of these
molecules include C.sub.11H.sub.11F.sub.3N.sub.2O.sub.2 (flutamide)
and C.sub.10F.sub.19O.sub.2K (potassium perfluorodecanoate).
[0072] Many linear or quasi-linear fluororganic compounds with
different substitution groups can be identified. For example, a
substitution group occurs when hydrogens of a molecule are replaced
with fluorine to create a fluorocarbon compound. Suitable compounds
include anesthetics and those listed in Table 2 below.
[0073] The C.sub.nH.sub.2n+2 molecules may be modeled as a
resonator. The length of the molecule is inversely proportional to
the number of carbons ("n") in the hydrocarbon chain, if n is
relatively large. The present inventors have discovered that the
fluororganic compounds experience a longitudinal acoustic mode
(LAM) and a longitudinal optical mode (LOM) frequency shift. These
shifts are dependent on the number of carbons in the molecule
chain.
[0074] A Raman spectra was obtained using an argon laser at about
488.0 nm or a copper-vapor laser at about 510.5 nm. The laser power
was about 100 mW. A computerized DFC-24 recording spectrometer with
1 cm.sup.-1 slit width was employed which was capable of monitoring
the position of the gratings. The samples were clear liquid or
white crystalline powders. Quartz cuvettes with parallel windows
and close fitting tops were used for liquid samples. Raman
observations were made at 90-degrees from the incident
radiation.
[0075] FIG. 11 shows Raman spectra in the region 0-1400 cm.sup.-1
for C.sub.nF.sub.2n+1Br. A sharp peak in the region 719-730
cm.sup.-1 was observed for all Raman spectra. This peak corresponds
to the fully symmetrical normal vibration of CF.sub.2 bond. FIG. 12
illustrates that with an increase in n, the maximum peak increased
linearly. This means that the peak intensity depends on the length
of the molecule.
[0076] FIG. 12 illustrates an intensive peak in the region 0-500
cm.sup.-1 and overlapping bands in the region 200-300 cm.sup.-1 .
For n=6, 7, and 8, the observed lower frequency band (LAM) included
several components. For n=9, 10 and 14 the band did not have
splitting. A peak signal that was single was observed from C.sub.14
to C.sub.9. However, from C.sub.8 to C.sub.6, the peak began to
split.
[0077] FIGS. 12 and 13 show that lower frequency LAM 80-150
cm.sup.-1 and higher frequency regions LOM 700-750 cm.sup.-1 of
Raman spectra of C.sub.nF.sub.2n+1Br compounds depend on the number
of carbons in the molecule chain. The frequency of the LAM
decreases as n increases (FIG. 12). However, the frequency of LOM
increases when n increases (FIG. 3).
[0078] FIGS. 15 and 16 show Raman spectra of mixtures of
fluoroorganic compounds in the spectral area characteristic for a
CF.sub.2 bond and the Raman spectra of such mixtures in the lower
frequency region LAM. At a concentration higher than about 2%, the
Raman peaks were identified for the certain type of the
fluoroorganic compound.
[0079] Table 2 below lists Raman spectral data for
C.sub.12F.sub.2n+1Br in the LAM and LOM frequency ranges.
2TABLE 2 Wave number, cm.sup.-1 Relative Intensity Bandwidth,
cm.sup.-1 Compound 77.7 3634 7.4 C.sub.14F.sub.29Br 100.9 1236 5.4
C.sub.10F.sub.21Br 111.4 1533 7.0 C.sub.9F.sub.19Br 117.5 1409 6.0
C.sub.8F.sub.17Br 134.6 4694 7.1 C.sub.7F.sub.15Br 142.1 4804 6.3
C.sub.6F.sub.13Br 730.3 2962 5.5 C.sub.14F.sub.29Br 727.3 2964 4.4
C.sub.10F.sub.21Br 725.4 3398 4.7 C.sub.9F.sub.19Br 723.9 5310 4.7
C.sub.8F.sub.17Br 721.1 5048 4.1 C.sub.7F.sub.15Br 719.8 5567 4.2
C.sub.6F.sub.13Br
[0080] Comparison of the different Raman spectra of mixtures of
fluororganic compounds indicates that the observed shifts depends
on the length of the molecules. The acoustic and optical modes of
vibration can be described using the dispersion law as follows:
.omega..sub.acoustic=2(S/a).times.sin.sup.2(ka/2) (1)
.omega..sub.optical=.omega..sub.0.sup.2-4(S.sup.2/a.sup.2).times.sin.sup.2-
(ka/2) (2)
[0081] where .omega..sub.acoustic is the frequency of the acoustic
mode; .omega..sub.optical is the frequency of the optical mode; k
is a vector which has a value of 2.pi./.lambda., where .lambda. is
the wavelength; a is the distance between atoms of a molecule
chain; S is the acoustical propagation speed.
[0082] The vector k and the frequencies .omega..sub.acoustic and
.omega..sub.optical can have various discrete values if the length
of the molecule chain is finite and has determined limits. Using
the shift of the acoustical and optical frequencies and plotting CF
molecular length of CF versus the frequency shift, the molecular
length ("L") of quasi-linear molecules in mixtures of fluorocarbon
molecules can be estimated. Accordingly, the minimum value for the
frequencies can be calculated as follows:
[0083] For f=.omega..sub.acoustic/2.pi. at the acoustic mode
LAM:
f.sub.acoustic=2(S/2.pi.a).times.sin(ka/2).congruent.(S/.pi.a).times.(.pi.-
a/2L)=(S/2L) (3)
[0084] where L>>a and k.sub.min=.pi./L.
[0085] For f=.omega..sub.optical/2.pi. at the optical mode LOM:
f.sub.optical.sup.2=f.sub.0.sup.2-4(S.sup.2/4.pi..sup.2a.sup.2).times.sin.-
sup.2(.pi.a/2L).congruent.f.sub.0.sup.2-S.sup.2/4L.sup.2 (4)
[0086] where L is the length of the molecule.
[0087] Assuming that .nu..sub.0=.omega..sub.0/2.pi.c,
.nu.=.omega./2.pi.c, and k.sub.mm=.pi./L, where .nu. and .nu..sub.0
are wave numbers, and c is the speed of light, the wavenumber
dependencies the length (L) of the molecule for the acoustical
(.nu..sub.acoustic) and optical (.nu..sub.optical) branches can be
calculated as:
.nu..sub.acoustic=(S/.pi.ac).times.sin (.pi.a/2L) (5)
.nu..sub.optical.sup.2=.nu..sub.0.sup.2-(S.sup.2/.pi..sup.2a.sup.2c.sup.2)-
.times.sin.sup.2 (.pi.a/2L) (6)
[0088] FIG. 14 illustrates experimental Raman frequencies indicated
by circles for C.sub.nF.sub.2n+1Br at n=6, 7, 8, 9, 10, and 14. The
experimental frequencies represent the values of the spectra
indicated in FIGS. 11 -13. FIG. 14 also illustrates calculated
frequencies, as indicated by solid lines, that match the above
spectra values. These calculations assume that L=na/2, where n is
the number of carbons, e.g., 6, 7, 8, 9, 10, and 14. Comparison of
the experimental and calculated frequencies indicates that actual
Raman frequencies for varying values of n can be accurately
calculated using the preferred method.
[0089] The dependency of the length of the molecule on the Raman
signal has been established in "quasi-one-dimensional" molecules of
fluororganic compounds. With an increase in the molecular length,
the high frequency (optical) mode LOM of CF.sub.2 linearly
increases, and the lower frequency (acoustical) mode LOM decreased.
Accordingly, the length of the molecular species in a mixture using
the changing optical and acoustical frequency modes can be
approximated.
[0090] Sample
[0091] The method of the invention can be used to analyze a variety
of samples. The method can identify fluoroorganic compounds in
liquid, gaseous, crystalline or amorphous solid states or in
solutions or suspensions of the fluoroorganic compounds in gases,
liquids, solids or multiphase media. The method is more sensitive
than other methods for detecting the carbon-fluorine bond of
fluoroorganic compounds, permitting detection of fluoroorganic
compounds at 10.sup.-3-10.sup.-6 g/L concentrations level. The
background of observation is naturally blank, which permits lower
detection limits. The sample can be aqueous solutions of water
soluble fluoroorganic compounds including those organic fluorine
compounds having low solubility in water or contain traces of
water. The method can be used on small solid samples or in solution
including aqueous solution. Mixtures can be used when one of the
compounds is a fluoroorganic compound, because the unique
carbon-fluorine Raman emission, centered around 730 cm.sup.-1 , is
characteristic for fluoroorganic compounds.
[0092] Thus, the invention permits the analysis of fluoroorganic
compounds where the compound is a drug, herbicide on vegetation, or
pesticide on vegetation or animals. The method can be used to
follow fluoroorganic compounds used as drugs in animals to
determine their presence and the presence of metabolites before
excretion. Applications include pharmaceutical research and
development, drug clinical trials, drug manufacturing, medical and
biomedical applications. Also, organic fluorine compounds or
derivatives which contaminate the environment can be detected at
the nanogram level. Applications include environmental analysis of
water, soil and air contaminated with fluoroorganic compounds,
continuous monitoring of manufacturing fluorocarbon products and
intermediates, and other similar applications. The method is thus
useful in quality control for industrial firms working with
fluoroorganic compounds. Dielectrics containing carbon-fluorine
bonds are a further area of interest. The ultimate environmental
fate of many fluorocarbon refrigerants is trifluoroacetic acid,
which has been found in wetlands in environmental studies. The
method is a superior analytical technique to permit analyzing large
numbers of soil samples for trifluoroacetic acid or for agriculture
fluorinated pesticides. Moreover, the method can greatly reduce the
research cost for developing new fluoroorganic pharmaceutical
preparations, herbicides, and pesticides.
[0093] Quantitation of fluoroorganic compounds in a sample can be
achieved by the method of the invention. When an analyst knows the
organic fluorine compound present and measures the number of
carbon-fluorine bonds, the molar amount of the fluoroorganic
compound can be determined.
[0094] The invention has applications with respect to detecting
other carbon-halogen bonds, including carbon-chlorine,
carbon-bromine, carbon-iodine, and carbon-astatine.
[0095] A number of embodiments of the present invention have been
described. Nevertheless, it will be understood that various
modifications may be made without departing from the spirit and
scope of the invention. The copper-vapor laser-based Raman
spectrograph described above may find broader applications.
Accordingly, other embodiments are within the scope of the
following claims.
* * * * *