WO2017076883A1

WO2017076883A1 - Use of a substituted zinc phthalocyanine as a sensitive material in a chemical sensor for detecting the presence of drugs in a gaseous medium

Info

Publication number: WO2017076883A1
Application number: PCT/EP2016/076396
Authority: WO
Inventors: Franck Pereira; Christelle Barthet; Stéphanie BESNARD; Lucie EPENOY
Original assignee: Commissariat A L'energie Atomique Et Aux Energies Alternatives
Priority date: 2015-11-03
Filing date: 2016-11-02
Publication date: 2017-05-11
Also published as: FR3043209A1; FR3043209B1; EP3371587A1

Abstract

The invention relates to the use of a substituted zinc phthalocyanine of the following formula as a sensitive material in a chemical sensor for detecting, in a gaseous medium, the presence of at least one compound selected from opiates, cocaine, cannabinoids, amphetamines, lysergic acid diethylamide, cathine, cathinone, synthetic derivatives of cathinone, γ-hydroxybutyric acid, ketamine, isoamyl nitrite, n -amyl nitrite, the isomers thereof, the salts thereof, the esters thereof, the ethers thereof, the precursors thereof and the degradation products thereof. Applications of the invention: control of drug trafficking, detection of illicit consumption of drugs in public spaces or as part of security checks or judicial inquiries.

Description

USE OF A SUBSTITUTED ZINC PHTHALOCYANINE AS A SENSITIVE MATERIAL IN A CHEMICAL SENSOR FOR DETECTING THE PRESENCE OF NARCOTIC DRUGS IN A GASEOUS MEDIUM

DESCRIPTION

TECHNICAL AREA

The present invention relates to the field of narcotics detection.

More specifically, it relates to the use of a substituted zinc phthalocyanine as a sensitive material in a chemical sensor which is intended to detect the presence of narcotics, their precursors and / or their degradation products in a gaseous medium. and, in particular, opiates, cocaine, cannabinoids, amphetamines, lysergic acid diethylamide (or LSD), cathine and cathinone (which are two alkaloids present in khat), synthetic derivatives of cathinone, γ-hydroxybutyric acid (also called "rapist drug"), ketamine, isoamyl nitrite and n-amyl nitrite (which are part of the poppers), as well as their isomers, their salts, their esters and their ethers.

The invention finds particular application in the fight against drug trafficking, also called narcotrafic.

It is also used in the detection of the illegal consumption of narcotics in public places, whether public or private, such as schools (colleges, high schools, universities, etc.), sports facilities, public transport. , railway stations, airports, administrations, businesses, nightclubs, etc., as well as within the framework of security controls (roadside checks for example) or judicial investigations. STATE OF THE PRIOR ART

According to the World Health Organization, drug trafficking is the third largest dollar trade in the world, behind those of oil and food, but just ahead of arms and medicine.

In addition to causing real health problems (overdose deaths, transmission of infectious agents like HIV or HCV) and social problems, drug trafficking generates specific crime and the creation of mafia type networks, with their contingent of gang wars, settling of scores, etc.

The fight against drug trafficking is therefore a major issue. However, it implies that the services in charge of this fight and, in particular, the customs and police services may have means enabling them to detect on site the presence of narcotics, particularly in the surrounding air.

Currently, the most commonly used method for on-site drug vapor detection is the use of sniffer dogs trained and trained for this purpose. However, the use of sniffer dogs has the disadvantage of requiring a long training of dogs and their masters and being unsuited to prolonged operations because of the fact that dogs' attention span is limited. In addition, sniffer dogs are not able to detect narcotics to which they have not been sensitized.

We are therefore looking more and more to replace sniffer dogs with portable devices.

In the field of portable devices, there are devices that detect narcotics by ion mobility spectrometry. These devices have the advantage of allowing a rapid detection (in a few tens of seconds at most) and low costs of the presence of narcotics. On the other hand, ionic mobility spectrometry is a powerful technique for detecting the presence of narcotic drugs on surfaces, but it proves to be much less reliable when it comes to detecting narcotics in the form of vapors. In addition, this technique requires the presence of a radioactive source, which means that the devices can only be used under the responsibility of a person competent in radiation protection and by persons with notions of radiation protection.

In recent years, the development of sensors able to detect in real time gaseous chemical species is in full swing. The operation of these sensors is based on the use of a film of a sensitive material, that is to say of a material of which at least one physical property P (mass, temperature, electrical conductivity, absorbance, fluorescence , etc.) is modified in contact with the desired gas molecules, which has a system capable of measuring in real time any variation of this physical property and thus highlight the presence of the desired gas molecules.

The advantages of chemical sensors are multiple: instantaneous results, possibility of miniaturization and, therefore, portability, maneuverability and significant autonomy, low manufacturing and operating costs, etc. By cons, it is obvious that their performance is extremely variable depending on the nature of the sensitive material used.

To date, sensitive materials that have been proposed for the detection of narcotic vapors are limited to molecularly imprinted polymers containing lanthanide complexes, and to antigen / antibody complexes using immunoassays (US 2003/0003587, [1], Stubbs et al., IEEE Sensors Journal 2005, 5, 335-339, [2], Frisk et al., Lab on a Chip 2008, 8, 1648-1657, [3]), which is very little.

It is, moreover, known to use metallated or non-metallated phthalocyanines as sensitive materials in devices intended to detect gases and, in particular, halogenated gases, nitrogen oxides, in particular N0 ₂ , and Ozone (Paoletti et al., Sensors 2009, 9, 5277-5297 [4], Brunet et al., Thin Solid Films 2005, 490, 1, 28-35

[5]). On the other hand, to the knowledge of the inventors, the use of phthalocyanines and, in particular, of substituted zinc phthalocyanines as sensitive materials for detecting the presence of narcotic drugs in a gaseous medium has never been proposed to date. However, as part of their work on the development of chemical sensors for the detection of narcotics, the inventors have found that a zinc phthalocyanine substituted by octyloxy (or octoxy) groups reacts with a very high sensitivity to vapors. a number of narcotics and is therefore likely to be a sensitive material of choice for chemical sensors for detecting the presence of these narcotics in a gaseous medium.

And it is on this observation that the present invention is based.

STATEMENT OF THE INVENTION

The subject of the invention is therefore the use of a substituted zinc phthalocyanine of the following formula:

as a sensitive material in a chemical sensor for detecting the presence in gaseous medium of at least one compound selected from opiates, cocaine, cannabinoids, amphetamines, lysergic acid diethylamide, cathine, cathinone, synthetic derivatives of cathinone, γ-hydroxybutyric acid, ketamine, isoamyl nitrite, n-amyl nitrite, their isomers, their salts, their esters, their ethers, their precursors and their degradation products.

The substituted zinc phthalocyanine shown above is commonly referred to as zinc 2,3,9,10,16,17,23,24-octakis (octyloxy) -29 / -β- / phthalocyanine. It is available from Sigma Aldrich under the reference 459720.

It will be called more simply PcZn (Ooct) s in what follows.

In the foregoing and the following, "narcotic" means any psychotropic substance whose production, trade, transport, import, export, possession, use and consumption are unlawful or subject to regulation.

By "psychotropic" is meant any chemical substance, of natural or synthetic origin, which acts on the central nervous system by inducing changes in perception, sensations, mood or consciousness.

"Opioid" means any compound that acts on opiate receptors in humans and that is either naturally present in opium such as: morphine, codeine or thebaine, or is synthetically obtained as heroin, hydromorphone, hydrocodone, oxymorphone, oxycodone, methadone, tilidine, tramadol, buprenorphine, fentanyl or dihydrocodeine.

By "cannabinoid" is meant any compound that acts on the cannabinoid receptors in humans and is naturally present in cannabis such as: 9-tetrahydrocannabinol (or THC) or tetrahydrocannabivarin, or is synthetically obtained as -pentyl-3- (1-naphthoyl) indole (or JWH-018), 2 - [(1R, 3S) -3-hydroxycyclohexyl] -5- (2-methyloctan-2-yl) phenol (or CP 47,497) 2 - [(1R, 3S) -3-hydroxycyclohexyl] -5- (1,1-dimethylhexyl) phenol (or (C6) -CP 47,497), 2 - [(1R, 3S) -3-hydroxycyclohexyl) 1- (2-methylnonan-2-yl) phenol (or (C8) -CP 47,497), 2 - [(1R, 3S) -3-hydroxycyclohexyl] -5- (2-methyldecan-2-yl) phenol (or (C9) -CP 47,497), or (6a, 10a) -9- (hydroxymethyl) -6,6-dimethyl-3- (2-methyl-octan-2-yl) -6a, 7 10,10-tetrahydrobenzo [c] -chromen-1-ol (or HU-210).

The term "amphetamine" means any compound derived from phenylethylamine by methylation of the carbon atom located in a of the amino group of phenylethylamine, such as: amphetamine sensu stricto, 4-fluoroamphetamine, 4- methylamphetamine (or 4-MA), methamphetamine, 3,4-methylene-dioxy- / V-methylamphetamine (or MDMA, better known as ecstasy), 3,4-methylenedioxy- / V-ethylamphetamine ( or MDEA), 3,4-methylenedioxy-amphetamine (or MDA), or 2,5-dimethoxy-4-methylamphetamine (or DOM).

The term "synthetic derivative of cathinone" means any compound derived from cathinone by substitution of one or more carbon atoms of the phenyl group of the cathinone and / or by substitution of the nitrogen atom of the amino group of the cathinone. cathinone such as: ephedrone (or methcathinone), methedrone (or 4-methoxymethinone), ethylcathinone, butylone, mephedrone, methylone, amphetamrone, metamfepramone, ethylcathinone (or ethylcathinone), or flhephedrone.

According to the invention, the PcZn (Ooct) s is present in the sensor preferably in the form of a thin film which covers one or both sides of a suitably selected substrate depending on the physical property whose variations are intended to be measured by this sensor.

Alternatively, the PcZn (Ooct) s can also be present in the sensor in the form of a massive object such as, for example, a cylinder having a certain porosity so as to make accessible to the compounds that it is desired to detect the together the molecules of this phthalocyanine.

When the PcZn (Ooct) is in the form of a thin film, this film preferably has a thickness of 1 nanometer to 10 microns and more preferably 10 nanometers to 1 micrometer.

Such a film can be obtained by any of the techniques proposed to date for making a thin film on the surface of a substrate and, in particular, by so-called "wet" deposition techniques because requiring the solution in solution of PcZn (Ooct) s in a volatile organic solvent of the chloroform type, such as spray deposition, spin coating ("spin coating" in English), deposition by drop, deposition-evaporation (or "Drop coating" in English) or soaking-withdrawal (or "dip coating" in English), or by the deposition techniques that do not require dissolution of this phthalocyanine as sublimation. The substrate and the measurement system of the sensor are chosen according to the physical property of the PcZn (Ooct) s whose variations induced by the presence of the compounds to be detected are intended to be measured by the sensor.

In the present case, the variations in mass of the PcZn (Ooct) s, deposited on a piezoelectric substrate (or resonator) of the quartz microbalance or surface acoustic wave (or Surface Acoustic Wave) type, have proved particularly interesting to measure.

Also, the sensor is preferably a gravimetric sensor and, more specifically, a quartz microbalance sensor or a surface acoustic wave sensor. The operating principle of these sensors has been described by Sanchez-Pedrono et al. in Analitica Chimica Acta 1986, 182, 285 [6] for quartz microbalance sensors, and by Hoummady et al. in Smart Materials and Structures 1997, 6, 647-657 [7] for SAW sensors.

Of course, it is also possible to use the PcZn (Ooct) s as a sensitive material in sensors designed to measure variations of a physical property other than the mass such as, for example, optical sensors based on the measurement of variations. of fluorescence, on the measurement of absorbance variations in the UV-visible range or on the measurement of wavelength variations in the infrared range.

Furthermore, it is also possible to gather within the same device or "multisensor", several elementary sensors comprising sensitive materials different from each other, or provided with substrates and measuring systems different from each other, l It is essential that at least one of these sensors include PcZn (Ooct) s as a sensitive material.

The use of PcZn (Ooct) s as a sensitive material in sensors for detecting the aforementioned narcotic drugs, their isomers, their salts, their esters, their ethers, their precursors and their degradation products has proved to be numerous. advantages.

Indeed, besides this phthalocyanine is very sensitive to all of these substances when present in a a gaseous medium, it reacts to the presence of these substances in an immediate or almost immediate, reproducible and reversible manner.

It can also be easily implemented in the form of thin films, either by so-called wet deposition techniques, or by sublimation, and thus makes it possible to envisage the manufacture of miniaturized sensors, easily transportable and manipulable on all types of sites, at costs compatible with the production of sensors on an industrial scale.

According to the invention, the compound to be detected is, preferably, methyl benzoate, cocaine, heroin, an amphetamine or isoamyl nitrite.

Other features and advantages of the invention will appear better on reading the additional description which follows, which relates to examples of the use of PcZn (Ooct) s as a sensitive material in gravimetric sensors and property demonstration. of these sensors.

Of course, these examples are given only as illustrations of the subject of the invention and do not constitute in any way a limitation of this object.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 represents the evolution of the oscillation frequency (F), expressed in Hz (hertz), as a function of the time (t), expressed in seconds, of a quartz microbalance sensor comprising a thin film of PcZn (Ooct) s, when this sensor is exposed successively to the ambient air and vapors of methyl benzoate which is a degradation product of cocaine in the presence of water vapor.

FIG. 2 represents the variations of the oscillation frequency (AF), expressed in Hz, as a function of the time (t), expressed in seconds, of a quartz microbalance sensor comprising a thin film of PcZn (Ooct) s , when this sensor is successively exposed to the ambient air and isoamyl nitrite vapor which is one of the main component of the poppers.

FIG. 3 represents the evolution of the oscillation frequency (F), expressed in Hz, as a function of the time (t), expressed in seconds, of a microwave sensor. quartz balance comprising a thin film of PcZn (Ooct) s, when this sensor is successively exposed to ambient air and to cocaine vapors.

FIG. 4 represents the evolution of the oscillation frequency (F), expressed in Hz, as a function of the time (t), expressed in seconds, of a quartz micro-balance sensor comprising a thin film of PcZn ( Ooct) s, when this sensor is successively exposed to ambient air and heroin vapors.

FIG. 5 represents the evolution of the oscillation frequency (F), expressed in Hz, as a function of the time (t), expressed in seconds, of a quartz microbalance sensor comprising a thin film of PcZn (Ooct) s, when this sensor is successively exposed to ambient air and amphetamine vapors.

FIG. 6 represents the evolution of the oscillation frequency (F), expressed in Hz, as a function of the time (t), expressed in seconds, of a SAW sensor comprising a thin film of PcZn (Ooct) s, when this sensor is successively exposed to ambient air and to methyl benzoate vapors.

FIG. 7 represents the evolution of the oscillation frequency (F), expressed in Hz, as a function of the time (t), expressed in seconds, of a SAW sensor, comprising a thin film of PcZn (Ooct) s, when this sensor is successively exposed to ambient air and to isoamyl nitrite vapors.

DETAILED DESCRIPTION OF PARTICULAR EMBODIMENTS EXAMPLE 1 Detection of Methyl Benzoate Vapor (Cocaine Degradation Product in the Presence of Water Vapor) by a Quartz Microbalance Sensor

In this example, a quartz microbalance sensor is made by covering the two faces of a cut crystal AT, with a nominal oscillation frequency of 9 M Hz, provided with two circular gold measuring electrodes (model Q.A9RA -50, Ametek Precision I nstruments), a thin film of PcZn (Ooct) s (Sigma-Aldrich, reference 459720).

The deposition of this thin film is carried out by performing on the two faces of quartz 5 sprays of 0.1 second each of a solution of PcZn (Ooct) in chloroform, with a concentration of 15 g / l. The variation of the oscillation frequency of the sensor related to this deposit is 10 kHz.

The sensor is subjected to detection tests which are carried out at 20 ° C and which consist of exposing it successively to:

. ambient air for 10 minutes (600 seconds);

methyl benzoate at a concentration of 350 ppm in ambient air for 5 minutes (300 seconds); and

ambient air for 5 minutes.

FIG. 1 illustrates the evolution of the frequency of oscillation (F) of the sensor, expressed in Hz, as a function of time (t), expressed in seconds, as obtained during these tests.

As shown in this figure, there is a drop in the oscillation frequency of the sensor in the presence of methyl benzoate vapors, which begins to occur as soon as the sensor is brought into contact with these vapors. This frequency drop is reversible since bringing the sensor into contact with the ambient air immediately causes a rise in its oscillation frequency.

It should be noted that, in the field of quartz microbalance sensors, a variation of the oscillation frequency of a sensor is considered significant and therefore exploitable when it is greater than three times the noise of a sensor. bottom of this sensor, about 10 Hz in this case.

However, as shown in FIG. 1, the fall in the oscillation frequency of the sensor induced by the exposure to methyl benzoate vapors is very much greater than this threshold value since it is 500 Hz, which means that the PcZn (Ooct) s present in the sensor is very sensitive to methyl benzoate vapors.

EXAMPLE 2: Detection of isoamyl nitrite vapor (constituting poppers) by a quartz microbalance sensor

In this example, a quartz microbalance sensor identical to that used in Example 1 above is used. This sensor is subjected to detection tests which are carried out at 20 ° C and which consist of exposing it successively to:

ambient air for 10 minutes (600 seconds);

isoamyl nitrite at a concentration of 35,000 ppm in ambient air for 5 minutes (300 seconds); and

ambient air for 5 minutes.

FIG. 2 illustrates the evolution of the frequency of oscillation (F) of the sensor, expressed in Hz, as a function of time (t), expressed in seconds, as obtained during these tests.

As shown in this figure, there is a drop in the oscillation frequency of the sensor in the presence of isoamyl nitrite vapor, which begins to occur as soon as the sensor is brought into contact with these vapors and which is reversible since the The return of the sensor to the ambient air immediately results in a return of its oscillation frequency to its initial value or to a value close to it.

Here again, the drop in the oscillation frequency of the sensor induced by exposure to isoamyl nitrite vapor, which is of the order of 600 Hz, shows a very high sensitivity of the PcZn (Ooct) s vis-à-vis the vapors of this narcotic.

EXAMPLE 3: Detection of cocaine vapors by a quartz microbalance sensor

In this example, a quartz microbalance sensor identical to those used in Examples 1 and 2 above is used.

This sensor is subjected to detection tests which are carried out at 20 ° C and which consist of exposing it successively to:

ambient air for 10 minutes (600 seconds);

cocaine at a concentration of 0.02 ppb in ambient air for 5 minutes (300 seconds); and

ambient air for 5 minutes.

FIG. 3 illustrates the evolution of the frequency of oscillation (F) of the sensor, expressed in Hz, as a function of time (t), expressed in seconds, as obtained during these tests. As shown in this figure, there is a drop in the oscillation frequency of the sensor in the presence of cocaine vapor, which begins to occur as soon as the sensor is brought into contact with these vapors. The decrease of the frequency of oscillation of the sensor is of the order of 60 Hz. EXAMPLE 4: Detection of heroin vapors by a quartz microbalance sensor

In this example, a quartz microbalance sensor identical to those used in Examples 1 to 3 above is used.

. ambient air for 10 minutes (600 seconds);

heroin at a concentration of 0.4 ppt in ambient air for 5 minutes (300 seconds); and

ambient air for 5 minutes.

FIG. 4 illustrates the evolution of the frequency of oscillation (F) of the sensor, expressed in Hz, as a function of time (t), expressed in seconds, as obtained during these tests.

As shown in this figure, there is a drop in the frequency of oscillation of the sensor in the presence of heroin vapors, which begins to occur as soon as the sensor is brought into contact with these vapors. The decrease of the oscillation frequency of the sensor is of the order of 45 Hz.

EXAMPLE 5 Detection of Amphetamine Vapors by a Quartz Microbalance Sensor

In this example, a quartz microbalance sensor identical to those used in Examples 1 to 4 above is used.

ambient air for 10 minutes (600 seconds);

amphetamine sensu stricto at a concentration of 0.4 ppt in ambient air for 5 minutes (ie 300 seconds); and ambient air for 5 minutes.

FIG. 5 illustrates the evolution of the frequency of oscillation (F) of the sensor, expressed in Hz, as a function of time (t), expressed in seconds, as obtained during these tests.

As shown in this figure, there is a drop in the frequency of oscillation of the sensor in the presence of amphetamine vapors, which begins to occur as soon as the sensor is brought into contact with these vapors. The decrease of the oscillation frequency of the sensor is of the order of 110 Hz.

EXAMPLE 6 Detection of methyl benzoate vapors by a SAW sensor

In this example, a SAW sensor, with a nominal oscillation frequency of 433 MHz, is made by covering the two faces of the piezoelectric substrate of this sensor with a PcZn (Ooct) s thin film (Sigma-Aldrich, reference 459720). .

The deposition of this thin film is carried out by spraying 0.02 to 0.2 seconds of a solution of PcZn (Ooct) in chloroform, with a concentration of between 0.5 and 1 g / l.

ambient air for 10 minutes (600 seconds);

ambient air for 5 minutes.

FIG. 6 illustrates the evolution of the frequency of oscillation (F) of the sensor, expressed in Hz, as a function of time (t), expressed in seconds, as obtained during these tests.

As shown in this figure, there is an increase in the oscillation frequency of the sensor in the presence of methyl benzoate vapors, which begins to occur as soon as the sensor is brought into contact with these vapors. This increase in oscillation frequency is reversible since the fact of putting the sensor in contact with the ambient air immediately results in a return of the oscillation frequency to a value close to its initial value.

The increase in the oscillation frequency of the sensor induced by its exposure to methyl benzoate vapors is of the order of 12 000 Hz, which means that the PcZn (Ooct) s present in this sensor is very sensitive to vapors. of this compound.

EXAMPLE 7 Detection of Isoamyl Nitrite Vapors by a SAW Sensor

In this example, a SAW sensor identical to that used in Example 6 above is used.

ambient air for 10 minutes (600 seconds);

ambient air for 5 minutes.

FIG. 7 illustrates the evolution of the frequency of oscillation (F) of the sensor, expressed in Hz, as a function of time (t), expressed in seconds, as obtained during these tests.

This figure shows that the contacting of the sensor with isoamyl nitrite values leads to an increase in its oscillation frequency which is of the order of 30 000 Hz and which shows a very high sensitivity of PcZn (Ooct) is present in this sensor to isoamyl nitrite vapors.

This increase in oscillation frequency is reversible since the return of the sensor to the ambient air immediately results in a return of its oscillation frequency to a value close to its initial value. REFERENCES CITED

[1] US 2003/0003587

[2] Stubbs et al., IEEE Sensors Journal 2005, 5, 335-339

[3] Frisk et al., Lab on a Chip 2008, 8, 1648-1657

[4] Paoletti et al., Sensors 2009, 9, 5277-5297 [5] Brunet et al., Thin Solid Films 2005, 490, 1, 28-35

[6] Sanchez-Pedrono et al., Analitica Chimica Acta 1986, 182, 285

[7] Hoummady et al., Smart Materials and Structures 1997, 6, 647-657

Claims

1. Use of a substituted zinc phthalocyanine of the following formula:

as a sensitive material in a chemical sensor for detecting the presence in a gaseous medium of at least one compound selected from opiates, cocaine, cannabinoids, amphetamines, lysergic acid diethylamide, cathine, cathinone, synthetic derivatives of cathinone, γ-hydroxybutyric acid, ketamine, isoamyl nitrite, n-amyl nitrite, their isomers, their salts, their esters, their ethers, their precursors and their degradation products.

The use of claim 1, wherein the substituted zinc phthalocyanine is used in the form of a thin film covering one or both of a substrate of the sensor.

The use of claim 2, wherein the thin film is 1 nanometer to 10 microns thick.

4. Use according to any one of claims 1 to 3, wherein the sensor is a gravimetric sensor.

Use according to claim 4, wherein the sensor is a quartz microbalance sensor or a surface acoustic wave sensor.

The use according to any one of claims 1 to 5, wherein the compound is methyl benzoate, cocaine, heroin, amphetamine or isoamyl nitrite.