CA2022558A1 - Optical oxygen sensor - Google Patents
Optical oxygen sensorInfo
- Publication number
- CA2022558A1 CA2022558A1 CA002022558A CA2022558A CA2022558A1 CA 2022558 A1 CA2022558 A1 CA 2022558A1 CA 002022558 A CA002022558 A CA 002022558A CA 2022558 A CA2022558 A CA 2022558A CA 2022558 A1 CA2022558 A1 CA 2022558A1
- Authority
- CA
- Canada
- Prior art keywords
- pyrene
- perylene
- group
- hydroxyundecyloxymethyl
- oxygen sensor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/03—Ethers having all ether-oxygen atoms bound to acyclic carbon atoms
- C07C43/14—Unsaturated ethers
- C07C43/178—Unsaturated ethers containing hydroxy or O-metal groups
- C07C43/1782—Unsaturated ethers containing hydroxy or O-metal groups containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
- C07C217/08—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to an acyclic carbon atom
- C07C217/10—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/64—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
- C07C309/68—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a carbon skeleton substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/18—Monohydroxylic alcohols containing only six-membered aromatic rings as cyclic part
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N31/00—Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods
- G01N31/22—Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods using chemical indicators
- G01N31/223—Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods using chemical indicators for investigating presence of specific gases or aerosols
- G01N31/225—Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods using chemical indicators for investigating presence of specific gases or aerosols for oxygen, e.g. including dissolved oxygen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/40—Ortho- or ortho- and peri-condensed systems containing four condensed rings
- C07C2603/42—Ortho- or ortho- and peri-condensed systems containing four condensed rings containing only six-membered rings
- C07C2603/50—Pyrenes; Hydrogenated pyrenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/52—Ortho- or ortho- and peri-condensed systems containing five condensed rings
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/0004—Gaseous mixtures, e.g. polluted air
- G01N33/0009—General constructional details of gas analysers, e.g. portable test equipment
- G01N33/0027—General constructional details of gas analysers, e.g. portable test equipment concerning the detector
- G01N33/0036—General constructional details of gas analysers, e.g. portable test equipment concerning the detector specially adapted to detect a particular component
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Optics & Photonics (AREA)
- Emergency Medicine (AREA)
- Dispersion Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Abstract An optical oxygen sensor which is based on a transfer of electromagnetic energy from a donor to an acceptor is described.
Pyrene derivatives of the general formula I
wherein R signifies an alkyl group with up to 30 C atoms which is substituted with a hydroxy or amino group or a group of the formula -NH(1-8C alkyl), a group -CH2-OR in which R has the aforementioned significance, a group -OR in which R has the aforementioned significance or a group -R'-O-R'' in which R' signifies an alkylene group, R'' has the above significance of R and R' and R'' together have not more than 30 C atoms and n signifies a whole number of 1-10, are used as the O2-indicators or as the donors.
1-Hydroxymethylpyrene, 1-(11-hydroxyundecyl)pyrene, 1-(11-hydroxyundecyloxymethyl)pyrene and 1-(2-aminoethyl-oxymethyl)pyrene are preferred pyrene derivatives.
Perylene derivatives of the general formula II
wherein R and n have the aforementioned significance, are used as the acceptors.
3-Hydroxymethylperylene, 11-amino-1-(3-perylene-methoxy)undecane, 3-(2-aminoethyloxymethyl)perylene and 3-(11-hydroxyundecyloxymethyl)perylene are preferred acceptors.
Pyrene derivatives of the general formula I
wherein R signifies an alkyl group with up to 30 C atoms which is substituted with a hydroxy or amino group or a group of the formula -NH(1-8C alkyl), a group -CH2-OR in which R has the aforementioned significance, a group -OR in which R has the aforementioned significance or a group -R'-O-R'' in which R' signifies an alkylene group, R'' has the above significance of R and R' and R'' together have not more than 30 C atoms and n signifies a whole number of 1-10, are used as the O2-indicators or as the donors.
1-Hydroxymethylpyrene, 1-(11-hydroxyundecyl)pyrene, 1-(11-hydroxyundecyloxymethyl)pyrene and 1-(2-aminoethyl-oxymethyl)pyrene are preferred pyrene derivatives.
Perylene derivatives of the general formula II
wherein R and n have the aforementioned significance, are used as the acceptors.
3-Hydroxymethylperylene, 11-amino-1-(3-perylene-methoxy)undecane, 3-(2-aminoethyloxymethyl)perylene and 3-(11-hydroxyundecyloxymethyl)perylene are preferred acceptors.
Description
2~22~8 The present invention i~ concerned with an opSical oxygen 6ensor. Such sensors i'requently consist of a photo-conductive medium to which an oxygen-sensitive layer has been applied. Such sensors can be implanted in a patient and serve especially for monitoring the oxygen content in the case of intensive care patients.
Optical oxygen (2) sensor6 have been described in the patent literature and in the literature, see e.;g.
European Patent Application, Publication No. 91,390, European Patent Application, Publication No. 262,578 and Jo~rnal of Optical Sensors, 1986, Vol. 1, No. 1, pp. 43-67.
. -For example, in the case of these sen60rs light can be coupled into a glass fibre tphotoconductive medium) via an optic and a dichroic reflector. This activates the 02-indicator at the end of the glass fibre in the o2-sensitive layer.~The fluorescent light of the 25 ~ -~indicator is collected in the glass fibre and is led ~; -back by this to the input of the fibre. This fluorescent light is fed to the photomultiplier via the dichroic reflecto~, interference filter and lenses. Information ` relating to fluorescence intensi~y and, respectively, fluorescence!'lifetime is possible from the signàl of thé
photomultiplier with the aid of an electronic evaluation. ;~
The two values~ can be related to the 02-concentration in the vicinity of the 02-sensitive layer.
The 02-sensitive element of a pO2-sensor can be formed from two fundamentally different types.
'~
Kltl27 . 6 . 90 .
~2~8 The 02-sensitive layer can be applied to the end of the fibre. The excitation light emerges from the end of the fibre and stimulates the fluorescence of the 02-indicato~s. Since the radiated ~luo~escent light is distributed isotropically, a portion thereof is coupled into the fibre and fed to the photomultiplier by the fibre.
The sensitive layer can replace the coating of the fibre ove~ a certain distance. In this embodiment of the sen~itive element, the excitation light is caIried in the core of the glas~ fibre over the entire region of the sensitive layer. The recipcocal action of the 2--indica~ors with the excitation light takes place via the so-called evanescent field (a part of the electro-magnetic field which in the case of total reflection infiltrates into the optically thinner medium). Of this excitation there are only affected indicators which are situated within the range of this evanescent field. The coupling-in of the fluorescent light is effected here via ~: :
~; the~evanescent field. The 02-indicator molecules are incorporated in polymers, which are brought together under the collective term silicones. Polydimethylsiloxane i6 the most simplest representative of this clas6. A large number of groups (e.g. alky`~l, phenyl, trifluoropropyl, vinyl, `~`
hydrogen etc.) can replace methyl as the substituent on ~ `
the silicon. Furthermore, individual repeating units can be replaced by branching eoints. This permits a cross-nking of the individual linear chains. The!consequence~
of this cross-linking are high-molecular silicon gums.
Silicon is chosen as the ca~rier material for the 2- ~--indicators because of its high 02-permeability and, rèspectively, 02-solubility.
The preparation of the silicon matrix is effected e.g.
starting from so-called RTV's (room temperature vulcanizing systems) which harden under the influence of ~ ':
- 2~22~8 atmospheric humidity. They generally contain acyloxy, amine, oxime or alkoxy residues as reactive groups. The RTV~s are dissolved in a solvent which contains the 02-indicator molecule. This solution i8 applied in a thin layer to the light-conducting substrate. The hardening of the polymer take6 place in contact with atmospheric humidity.
In accordance with the invention there serve as 02-indicatocs pycene derivatives or a combination of pyrene derivatives and perylene derivatives as a donor--acceptor pair (see Applied Spectroscopy Vol. 42, No. 6, 1988, p. 1009-1011~. Not only pyrene derivatives, but also the combination of pyrene derivatives and perylene derivatives possess the spectral requirements which ace placed on fluorescence indicators for an 02-detection.
The advantage of the pyrene derivative-perylene derivative combination over pyrene derivative resides mainly in the large difference between excitation wavelength and ~-emission wavelength. ~ .
For the "in vivo~ use of a pO2-sensor or for the introduction of additional layers on to the 02-sensitive layer (e.g. for the onstruction of an enzyme sensor based on a pO2-sensor), the leaching of indica~or molecules ;~
must be prevented. In the scope of the present invention it has now been found that, by suitably substituting these indicator-molqcules~, they can bè covalen,tly bonded to the polymer skeleton simultaneously with the hardening of the silicon matrix. This covalent bonding is based on the -~
reaction between the reactive groups of the RTV prepolymer as well as the reactive groups of the indicator molecule. ;~
Pyrene tierivatives of the general formula ~ ~
:: :
. .',' ~' ";
2~2'~8 ¢~` ( R ) n : wherein R signifies an alkyl group with up to 30 ~: C atoms which i6 sub6tituted with a hydroxy or amino :~
group or a group of the focmula -NH(1-8C alkyl), a qroup -CH2-OR in which R has the aforementioned - significance, a g~oup -OR in which R has the aforementioned significance oc a g~oup -R~-O-R~ in which R' signifies an alkylene gcoup, R~' has the above significance of R and R~ and R~' together have :-: not more than~30 C atoms and n ~ignifies a whole ~ .
number of 1-10, : are used a6 the O -indicators or:as donors.
- 2 ~ .
2 l-HydcoYymethylpyrene, l-tll-hydroxyundecyl)pyrene, hydroxyundecyIoxymethyl)pyrene and 1-(2-aminoethyl-oxymethyl)pyrene~a~e pLeferred pyrene derivatives. ~ -Perylene derivatives of the genecal formula 3 ~ (R)n . :
. ~,.; :
2~22~8 wherein R and n have the aforementioned significance, are used as the acceptors.
3 Hydroxymethylperylene, ll-amino-1-(3-perylene-methoxy)undecane, 3-(2-aminoethyloxymethyl)perYlene and 3-(11-hydroxyundecyloxymethy;L)perylene are preferred acceptors.
The pyrene or perylene derivatives are preferably present in a concentration of 10-4-10 2 mol/litre.
According to a first aspect, the present invention is accordingly concerned with an optical oxygen sensor~
containing a silicon matrix in which a pyrene derivative of general formula I is covalently bonded.
According to a further aspect, the present invention 20 i6 concerned with an optical oxygen sensor based on a transfer of electromagnetic ener~y from a donor to an ;;
acceptor, containing a silicon matrix in which a pyrene derivative of general formula I is covalently bonded as the donor and in which a perylene derivative of general formula II is covalently bonded as the acceptor.
According to a further aspect, the present invention ` is concerned with a silicon matrix fcr an optical oxygen sensor, in which a pyrene derivative of general formula I
is covalene1y~lbonded Finally, the present invention is concerned with a ~ silicon matrix for an optical oxygen sensor ba6ed on a ; transfer of electromagnetic energy from a donor to an acceptor, in which a pyrene derivative of general formula I is covalently bonded and serves as the donor and ~ -. .
in which a perylene derivative of general formula II is covalently l~onded and serves as the acceptor.
,:
2~22~
,.
The compounds of formulae I or II can be prepared in a manner known per se by alkylating pyrene or perylene with the correspondingly substituted alkyl halide in a Friedel Crafts reaction using a catalyst such as e.g. aluminium chloride in an inert ~olvent such as carbon tetrachloride, methylene chloride or in a deactivated liquid aromatic such as nitrobenzene, chlorobenzene, preferably methylene chloride, at 0-30C, preferably room temperature. The introduction of the alkyl groups i~ effected according to the substitution pattern of the electrophilic substitution which is characteristic for the particular aromatic. Aftec the usual working-up with ice-water and methylene chloride 15 the alkylation products can be separated by chcomatography. -~
The compounds of formula I or II in which R signifies CH2-OR R'-O-R'' or OR can be prepared by converting the corresponding hydroxy compound into the alcoholate by deprotonization with sodium hydride at 0C ~o room temperature in an inert solvent which is favourable for ~ the subsequent alkylationj such as tetrahydrofuran or ;~
; N,N-dialkylformamide, and reaction (after the H2- ;~
-evolution has ceased) with the correspondingly substituted alkyl halide at room temperature to give the correspondingly substituted alkoxy compounds.
The following Examples illustrate the invention~
ExamPle 1 2 g tlO mmol) of pyrene in 10 ml of dry methylene chloride are added dropwi&e to a suspension of 2.5 g -~
(10 mmol) of ll-bromoundecanol and 20 g (160 mmol) of aluminium chloride in 10 ml of methylene chloride, whereupon the mixture is stirred at room temperature for 16 hrs. The mixture i~ hydrolyzed with ice-water, extracted with methylene chloride and concentrated. ~ `
~: ' 3 ~ "~ ~ J
Chromatography i8 carried out with methylene chloride.
1.9 g (50~) of l~ hydroxyundecyl)pyrene are thereby obtained. HPLC (0.5% EtOAc/hexane): tR = 3 4 min.
(Ed = 2.1 min.).
_amPle 2 l.a6 g (8 mmol) of l-hydroxymethylpyrene are dissolved in 20 ml of dry DMF, treated with 300 mg (9 mmol) of ' ' sodium hydride (80~ in mineral oil) and stirred at room ' temperature for 30 min. Then. 2 g (8 mmol) of l-bromo-ll--undecanol are added dropwise and the mixture is stirred 15 at room temperature for 3 hrs. The mixture is treated with '~
ice-water, extracted with toluene and the ocganic pha~e is concentrated and chromatographed on silica gel. There are ; , obtained 3.4 g (99%) of l-(ll-hydroxyundecyloxymethyl)-~ ~ pyrene of meleing point 62-64 which is characterized by ~-~
;~ 20 MS and NMR. TLC (silica gel/toluene): Rf (educt) = 0.1, Rf ';~
(product) = 0.11; and HPLC (RPlB 125-4/MeCN): tR (educt) = ~' 2.3 min., tR (product) = 6.5 min.
ExamPle 3 ;, 282 mg (1 mmol) of 3-hydroxymethylperylene are ,~
dissolved in 5 ml of dry DMF, treated with 35 mg (1.2'mmol) of sodium hydride (80~ in mineral oil) and stirred at room temperature for 30 min. Then, .?~ g , 30~ ~(,l mm;o,l)~,of l-,bromo-ll-~undecanol is adde,d dropwise,jand ,the ,'~
mixture is stirred at room temperature fo~ 3 hrs. The ~, ` mixture is treated with ice-water, extracted with toluene ,,~
and the organic phase is concentrated and chromatographed '~
~ on silica glel. There are obtained 3.4 g (99%) of 3-(11-35 -hydroxyundecyloxymethyi)perylene of melting point ~
126-127 which i~ characterized by MS and NMR. TLC (silica ' ,, gel~toluene): Rf (educt~ = 0.1, Rf (product) = 0.11; and ,, HPLC (RP18 125-4/MeCNj: tR (educt) = 3.1 min., tR
(product) = 9.5 min.
-~- 2 ~ 2 2 ~
Example 4 6.20 g (27 mmol) of l-hydroxymethylpyrene are dissolved in 10 ml of dry DMF, treated with 760 mg (27 mmol) of sodium hydride (80% in mineral oil) and stirred at room temperature for 30 min. Then, 16 g (52 mmol) of l,ll-dibromoundecane are added dropwise and the mixture is stirred at room ~emperature for 16 hrs. The mixture is treated with ice-water, extracted with toluene and the organic phase is filtered through ~ilica gel and concentrated. Chromatography is carried out on silica gel with toluene. There are obtained 8.54 g (63%) of ll-bromo--l-tpyrenylmethyloxy)undecane of melting point 45-47DC
;~ which is characterized by MS and NMR. TLC (silica gel/
toluene): Rf (educt) = 0.1 and 0.9, Rf (product) = 0.8, Rf (product) = 0.5; and HPLC (RP18 125-4/MeCN): tR (educt) =
2.3 min., tR (product) = 4.6 min.
Example 5 ~, :
1 g (about 2 mmol) of ll-bromo-l-(l-pyrenemethyloxy)~
undecane is dissolved in 10 ml of THF and stirred at room tempecature overnight with 3 g of potassium phthalimide.
The mixture is concentrated and subsequently extracted with water and methylene chloride. After drying the methylene chloride solution is treated with 10 ml of hydrazine hydrate and stirred overnight. The mixture is concentrated, ~suspended!in ethanol, filtered and the , :~`
filtrate is concentrated. 0.8 g tabout 100%) of ll-amino-(l-pyrenylmethoxy)undecane is obtained. For purifica-tion for elementary analysis it is recrystallized from lN
hydrochloric: acid. 0.5 g of the corresponding hydro- ~
chloride is obtained. ~ ;
:, 2~2~
, .
Example 6 0.90 g (2 mmol) of 3~ hydroxyundecyloxymethyl)-perylene is dissolved in 10 ml of dry pyridine, treated with 500 mg (Z.5 mmol) of tosyl chloride and stirred at room temperature for 16 hrs. The mixture is then stirred with 10 ml of ice-water for 1 hr., treated with Hyflo and filtered. The re~idue is washed with water and then triturated with methylene chloride. The organic phase i8 : ~.
dried with sodium sulphate and concentrated. 1.2 g of ll-tosyloxy-1-(3-perylenemethyloxy)undecane are thus obtained. TLC on silica gel with toluene gave a Rf value f O.S.
; ExamPle 7 1.2 g (about 2 mmol) of 11-tosyloxy-1-(3-perylene-methyloxy)undecane are dis601Yed in 10 ml of THF and -~
stirred at room temperature overnight with 3 g of potas6ium phthalimide. The mixture is concentrated and ~ -sub6equently extracted with water and methylene chloride.
After drying the methylene chloride solution is treated `~
with 10 ml of hydrazine hydrate and stirred overnight. The mixture is concentrated, ~uspended in ethanol, filtered and the filtrate is concentrated. 0.9 (about 100%) of ll-amino-l-t3-perylenemethyloxy)undecane with a Rf value of 0.6 is thereby obtained. .
.
ExamRle 8 500 mg of l-hydroxymethylpyrene are dissolved in 10 ml of dry dimethylformamide and 100 mg of sodium hydride (55%
in mineral oil) are added at -20. The mixture is stirred for 30 min. and then 0.5 ml of 2-chloroethylamine is added droewise. The mixture is stir~ed at room temperature over-night, sub6equently treated with ethanol and then with 2a22~
water. The mixture is concentrated and recrystallized from chloroform/hexane. 410 mg of 1-(2-aminoethyloXymethyl)-pyrene are obtained.
Example 9 50 mg of 3-hydroxymethylE~erylene a~e reacted in analogy to Example 8 to give 3-(2-aminoethyloxymethyl)-perylene.
~ :~
Exam~le 10 ~Production of an 02-~ensitive la~er) -1 g of Elastosi 1 E 43 (Wacker Chemie) i6 dissolved in ~;
1 ml of a toluene solution of ~he indicator l-tll-hydroxy-undecyloxymethyl)pyrene (`concentration about 10 3 mol/l). The resulting viscous mass i8 applied to the glass substrate in the desired layer thickness. After - 20 hardening of the~polymer the non-covalently bonded indicator is washed from the polymer by rinsing with methylene chloride. ~ -,~ - ..
~ Exam~l~L~ L~ n of an o2-sensitive laYer~
-~ ~ 25 1 g of Ela~stosil~E 43 (Wacker Chemie) is dissolved in ml of a toluene~solution of l-~ll-hydroxyundecyloxy~
met~hyl)pyrene and 3~ hydroxyundecyloxymethyl)perylene (concentration about 10 mol~l). The resulting v~scous ,.
~ 30 mass i~s applied~to the~glass substrate in the desired ; ~ layer thickness. After hardening of the polymer the non~
covalently bonded indicators are washed from the polymer `~
by rinsing with methylene chloride.
3S ~
: ` ~-;:
: '
Optical oxygen (2) sensor6 have been described in the patent literature and in the literature, see e.;g.
European Patent Application, Publication No. 91,390, European Patent Application, Publication No. 262,578 and Jo~rnal of Optical Sensors, 1986, Vol. 1, No. 1, pp. 43-67.
. -For example, in the case of these sen60rs light can be coupled into a glass fibre tphotoconductive medium) via an optic and a dichroic reflector. This activates the 02-indicator at the end of the glass fibre in the o2-sensitive layer.~The fluorescent light of the 25 ~ -~indicator is collected in the glass fibre and is led ~; -back by this to the input of the fibre. This fluorescent light is fed to the photomultiplier via the dichroic reflecto~, interference filter and lenses. Information ` relating to fluorescence intensi~y and, respectively, fluorescence!'lifetime is possible from the signàl of thé
photomultiplier with the aid of an electronic evaluation. ;~
The two values~ can be related to the 02-concentration in the vicinity of the 02-sensitive layer.
The 02-sensitive element of a pO2-sensor can be formed from two fundamentally different types.
'~
Kltl27 . 6 . 90 .
~2~8 The 02-sensitive layer can be applied to the end of the fibre. The excitation light emerges from the end of the fibre and stimulates the fluorescence of the 02-indicato~s. Since the radiated ~luo~escent light is distributed isotropically, a portion thereof is coupled into the fibre and fed to the photomultiplier by the fibre.
The sensitive layer can replace the coating of the fibre ove~ a certain distance. In this embodiment of the sen~itive element, the excitation light is caIried in the core of the glas~ fibre over the entire region of the sensitive layer. The recipcocal action of the 2--indica~ors with the excitation light takes place via the so-called evanescent field (a part of the electro-magnetic field which in the case of total reflection infiltrates into the optically thinner medium). Of this excitation there are only affected indicators which are situated within the range of this evanescent field. The coupling-in of the fluorescent light is effected here via ~: :
~; the~evanescent field. The 02-indicator molecules are incorporated in polymers, which are brought together under the collective term silicones. Polydimethylsiloxane i6 the most simplest representative of this clas6. A large number of groups (e.g. alky`~l, phenyl, trifluoropropyl, vinyl, `~`
hydrogen etc.) can replace methyl as the substituent on ~ `
the silicon. Furthermore, individual repeating units can be replaced by branching eoints. This permits a cross-nking of the individual linear chains. The!consequence~
of this cross-linking are high-molecular silicon gums.
Silicon is chosen as the ca~rier material for the 2- ~--indicators because of its high 02-permeability and, rèspectively, 02-solubility.
The preparation of the silicon matrix is effected e.g.
starting from so-called RTV's (room temperature vulcanizing systems) which harden under the influence of ~ ':
- 2~22~8 atmospheric humidity. They generally contain acyloxy, amine, oxime or alkoxy residues as reactive groups. The RTV~s are dissolved in a solvent which contains the 02-indicator molecule. This solution i8 applied in a thin layer to the light-conducting substrate. The hardening of the polymer take6 place in contact with atmospheric humidity.
In accordance with the invention there serve as 02-indicatocs pycene derivatives or a combination of pyrene derivatives and perylene derivatives as a donor--acceptor pair (see Applied Spectroscopy Vol. 42, No. 6, 1988, p. 1009-1011~. Not only pyrene derivatives, but also the combination of pyrene derivatives and perylene derivatives possess the spectral requirements which ace placed on fluorescence indicators for an 02-detection.
The advantage of the pyrene derivative-perylene derivative combination over pyrene derivative resides mainly in the large difference between excitation wavelength and ~-emission wavelength. ~ .
For the "in vivo~ use of a pO2-sensor or for the introduction of additional layers on to the 02-sensitive layer (e.g. for the onstruction of an enzyme sensor based on a pO2-sensor), the leaching of indica~or molecules ;~
must be prevented. In the scope of the present invention it has now been found that, by suitably substituting these indicator-molqcules~, they can bè covalen,tly bonded to the polymer skeleton simultaneously with the hardening of the silicon matrix. This covalent bonding is based on the -~
reaction between the reactive groups of the RTV prepolymer as well as the reactive groups of the indicator molecule. ;~
Pyrene tierivatives of the general formula ~ ~
:: :
. .',' ~' ";
2~2'~8 ¢~` ( R ) n : wherein R signifies an alkyl group with up to 30 ~: C atoms which i6 sub6tituted with a hydroxy or amino :~
group or a group of the focmula -NH(1-8C alkyl), a qroup -CH2-OR in which R has the aforementioned - significance, a g~oup -OR in which R has the aforementioned significance oc a g~oup -R~-O-R~ in which R' signifies an alkylene gcoup, R~' has the above significance of R and R~ and R~' together have :-: not more than~30 C atoms and n ~ignifies a whole ~ .
number of 1-10, : are used a6 the O -indicators or:as donors.
- 2 ~ .
2 l-HydcoYymethylpyrene, l-tll-hydroxyundecyl)pyrene, hydroxyundecyIoxymethyl)pyrene and 1-(2-aminoethyl-oxymethyl)pyrene~a~e pLeferred pyrene derivatives. ~ -Perylene derivatives of the genecal formula 3 ~ (R)n . :
. ~,.; :
2~22~8 wherein R and n have the aforementioned significance, are used as the acceptors.
3 Hydroxymethylperylene, ll-amino-1-(3-perylene-methoxy)undecane, 3-(2-aminoethyloxymethyl)perYlene and 3-(11-hydroxyundecyloxymethy;L)perylene are preferred acceptors.
The pyrene or perylene derivatives are preferably present in a concentration of 10-4-10 2 mol/litre.
According to a first aspect, the present invention is accordingly concerned with an optical oxygen sensor~
containing a silicon matrix in which a pyrene derivative of general formula I is covalently bonded.
According to a further aspect, the present invention 20 i6 concerned with an optical oxygen sensor based on a transfer of electromagnetic ener~y from a donor to an ;;
acceptor, containing a silicon matrix in which a pyrene derivative of general formula I is covalently bonded as the donor and in which a perylene derivative of general formula II is covalently bonded as the acceptor.
According to a further aspect, the present invention ` is concerned with a silicon matrix fcr an optical oxygen sensor, in which a pyrene derivative of general formula I
is covalene1y~lbonded Finally, the present invention is concerned with a ~ silicon matrix for an optical oxygen sensor ba6ed on a ; transfer of electromagnetic energy from a donor to an acceptor, in which a pyrene derivative of general formula I is covalently bonded and serves as the donor and ~ -. .
in which a perylene derivative of general formula II is covalently l~onded and serves as the acceptor.
,:
2~22~
,.
The compounds of formulae I or II can be prepared in a manner known per se by alkylating pyrene or perylene with the correspondingly substituted alkyl halide in a Friedel Crafts reaction using a catalyst such as e.g. aluminium chloride in an inert ~olvent such as carbon tetrachloride, methylene chloride or in a deactivated liquid aromatic such as nitrobenzene, chlorobenzene, preferably methylene chloride, at 0-30C, preferably room temperature. The introduction of the alkyl groups i~ effected according to the substitution pattern of the electrophilic substitution which is characteristic for the particular aromatic. Aftec the usual working-up with ice-water and methylene chloride 15 the alkylation products can be separated by chcomatography. -~
The compounds of formula I or II in which R signifies CH2-OR R'-O-R'' or OR can be prepared by converting the corresponding hydroxy compound into the alcoholate by deprotonization with sodium hydride at 0C ~o room temperature in an inert solvent which is favourable for ~ the subsequent alkylationj such as tetrahydrofuran or ;~
; N,N-dialkylformamide, and reaction (after the H2- ;~
-evolution has ceased) with the correspondingly substituted alkyl halide at room temperature to give the correspondingly substituted alkoxy compounds.
The following Examples illustrate the invention~
ExamPle 1 2 g tlO mmol) of pyrene in 10 ml of dry methylene chloride are added dropwi&e to a suspension of 2.5 g -~
(10 mmol) of ll-bromoundecanol and 20 g (160 mmol) of aluminium chloride in 10 ml of methylene chloride, whereupon the mixture is stirred at room temperature for 16 hrs. The mixture i~ hydrolyzed with ice-water, extracted with methylene chloride and concentrated. ~ `
~: ' 3 ~ "~ ~ J
Chromatography i8 carried out with methylene chloride.
1.9 g (50~) of l~ hydroxyundecyl)pyrene are thereby obtained. HPLC (0.5% EtOAc/hexane): tR = 3 4 min.
(Ed = 2.1 min.).
_amPle 2 l.a6 g (8 mmol) of l-hydroxymethylpyrene are dissolved in 20 ml of dry DMF, treated with 300 mg (9 mmol) of ' ' sodium hydride (80~ in mineral oil) and stirred at room ' temperature for 30 min. Then. 2 g (8 mmol) of l-bromo-ll--undecanol are added dropwise and the mixture is stirred 15 at room temperature for 3 hrs. The mixture is treated with '~
ice-water, extracted with toluene and the ocganic pha~e is concentrated and chromatographed on silica gel. There are ; , obtained 3.4 g (99%) of l-(ll-hydroxyundecyloxymethyl)-~ ~ pyrene of meleing point 62-64 which is characterized by ~-~
;~ 20 MS and NMR. TLC (silica gel/toluene): Rf (educt) = 0.1, Rf ';~
(product) = 0.11; and HPLC (RPlB 125-4/MeCN): tR (educt) = ~' 2.3 min., tR (product) = 6.5 min.
ExamPle 3 ;, 282 mg (1 mmol) of 3-hydroxymethylperylene are ,~
dissolved in 5 ml of dry DMF, treated with 35 mg (1.2'mmol) of sodium hydride (80~ in mineral oil) and stirred at room temperature for 30 min. Then, .?~ g , 30~ ~(,l mm;o,l)~,of l-,bromo-ll-~undecanol is adde,d dropwise,jand ,the ,'~
mixture is stirred at room temperature fo~ 3 hrs. The ~, ` mixture is treated with ice-water, extracted with toluene ,,~
and the organic phase is concentrated and chromatographed '~
~ on silica glel. There are obtained 3.4 g (99%) of 3-(11-35 -hydroxyundecyloxymethyi)perylene of melting point ~
126-127 which i~ characterized by MS and NMR. TLC (silica ' ,, gel~toluene): Rf (educt~ = 0.1, Rf (product) = 0.11; and ,, HPLC (RP18 125-4/MeCNj: tR (educt) = 3.1 min., tR
(product) = 9.5 min.
-~- 2 ~ 2 2 ~
Example 4 6.20 g (27 mmol) of l-hydroxymethylpyrene are dissolved in 10 ml of dry DMF, treated with 760 mg (27 mmol) of sodium hydride (80% in mineral oil) and stirred at room temperature for 30 min. Then, 16 g (52 mmol) of l,ll-dibromoundecane are added dropwise and the mixture is stirred at room ~emperature for 16 hrs. The mixture is treated with ice-water, extracted with toluene and the organic phase is filtered through ~ilica gel and concentrated. Chromatography is carried out on silica gel with toluene. There are obtained 8.54 g (63%) of ll-bromo--l-tpyrenylmethyloxy)undecane of melting point 45-47DC
;~ which is characterized by MS and NMR. TLC (silica gel/
toluene): Rf (educt) = 0.1 and 0.9, Rf (product) = 0.8, Rf (product) = 0.5; and HPLC (RP18 125-4/MeCN): tR (educt) =
2.3 min., tR (product) = 4.6 min.
Example 5 ~, :
1 g (about 2 mmol) of ll-bromo-l-(l-pyrenemethyloxy)~
undecane is dissolved in 10 ml of THF and stirred at room tempecature overnight with 3 g of potassium phthalimide.
The mixture is concentrated and subsequently extracted with water and methylene chloride. After drying the methylene chloride solution is treated with 10 ml of hydrazine hydrate and stirred overnight. The mixture is concentrated, ~suspended!in ethanol, filtered and the , :~`
filtrate is concentrated. 0.8 g tabout 100%) of ll-amino-(l-pyrenylmethoxy)undecane is obtained. For purifica-tion for elementary analysis it is recrystallized from lN
hydrochloric: acid. 0.5 g of the corresponding hydro- ~
chloride is obtained. ~ ;
:, 2~2~
, .
Example 6 0.90 g (2 mmol) of 3~ hydroxyundecyloxymethyl)-perylene is dissolved in 10 ml of dry pyridine, treated with 500 mg (Z.5 mmol) of tosyl chloride and stirred at room temperature for 16 hrs. The mixture is then stirred with 10 ml of ice-water for 1 hr., treated with Hyflo and filtered. The re~idue is washed with water and then triturated with methylene chloride. The organic phase i8 : ~.
dried with sodium sulphate and concentrated. 1.2 g of ll-tosyloxy-1-(3-perylenemethyloxy)undecane are thus obtained. TLC on silica gel with toluene gave a Rf value f O.S.
; ExamPle 7 1.2 g (about 2 mmol) of 11-tosyloxy-1-(3-perylene-methyloxy)undecane are dis601Yed in 10 ml of THF and -~
stirred at room temperature overnight with 3 g of potas6ium phthalimide. The mixture is concentrated and ~ -sub6equently extracted with water and methylene chloride.
After drying the methylene chloride solution is treated `~
with 10 ml of hydrazine hydrate and stirred overnight. The mixture is concentrated, ~uspended in ethanol, filtered and the filtrate is concentrated. 0.9 (about 100%) of ll-amino-l-t3-perylenemethyloxy)undecane with a Rf value of 0.6 is thereby obtained. .
.
ExamRle 8 500 mg of l-hydroxymethylpyrene are dissolved in 10 ml of dry dimethylformamide and 100 mg of sodium hydride (55%
in mineral oil) are added at -20. The mixture is stirred for 30 min. and then 0.5 ml of 2-chloroethylamine is added droewise. The mixture is stir~ed at room temperature over-night, sub6equently treated with ethanol and then with 2a22~
water. The mixture is concentrated and recrystallized from chloroform/hexane. 410 mg of 1-(2-aminoethyloXymethyl)-pyrene are obtained.
Example 9 50 mg of 3-hydroxymethylE~erylene a~e reacted in analogy to Example 8 to give 3-(2-aminoethyloxymethyl)-perylene.
~ :~
Exam~le 10 ~Production of an 02-~ensitive la~er) -1 g of Elastosi 1 E 43 (Wacker Chemie) i6 dissolved in ~;
1 ml of a toluene solution of ~he indicator l-tll-hydroxy-undecyloxymethyl)pyrene (`concentration about 10 3 mol/l). The resulting viscous mass i8 applied to the glass substrate in the desired layer thickness. After - 20 hardening of the~polymer the non-covalently bonded indicator is washed from the polymer by rinsing with methylene chloride. ~ -,~ - ..
~ Exam~l~L~ L~ n of an o2-sensitive laYer~
-~ ~ 25 1 g of Ela~stosil~E 43 (Wacker Chemie) is dissolved in ml of a toluene~solution of l-~ll-hydroxyundecyloxy~
met~hyl)pyrene and 3~ hydroxyundecyloxymethyl)perylene (concentration about 10 mol~l). The resulting v~scous ,.
~ 30 mass i~s applied~to the~glass substrate in the desired ; ~ layer thickness. After hardening of the polymer the non~
covalently bonded indicators are washed from the polymer `~
by rinsing with methylene chloride.
3S ~
: ` ~-;:
: '
Claims (11)
1. An optical oxygen sensor containing a silicon matrix in which is covalently bonded a pyrene derivative of the general formula I
wherein R signifies an alkyl group with up to 30 C atoms which is substituted with a hydroxy or amino group or a group of the formula -NH(1-8C alkyl), a group -CH2-OR in which R has the aforementioned significance, a group -OR in which R has the aforementioned significance or a group -R'-O-R'' in which R' signifies an alkylene group, R'' has the above significance of R and R' and R'' together have not more than 30 C atoms and n signifies a whole number of 1-10, whereby the compound of formula I serves as the oxygen indicator.
wherein R signifies an alkyl group with up to 30 C atoms which is substituted with a hydroxy or amino group or a group of the formula -NH(1-8C alkyl), a group -CH2-OR in which R has the aforementioned significance, a group -OR in which R has the aforementioned significance or a group -R'-O-R'' in which R' signifies an alkylene group, R'' has the above significance of R and R' and R'' together have not more than 30 C atoms and n signifies a whole number of 1-10, whereby the compound of formula I serves as the oxygen indicator.
2. An optical oxygen sensor based on a transfer of electromagnetic energy from a donor to an acceptor, containing a silicon matrix in which a pyrene derivative of general formula I in which R and n have the afore-mentioned significance is covalently bonded and which acts as the donor and furthermore in which a perylene derivative of the general formula II
wherein R and n have the said significance, is covalently bonded and which serves as the acceptor.
wherein R and n have the said significance, is covalently bonded and which serves as the acceptor.
3. A silicon matrix for an optical oxygen sensor, in which a pyrene derivative of general formula I is covalently bonded and which serves as the O2-indicator.
4. A silicon matrix for an optical oxygen sensor based on a transfer of electromagnetic energy from a donor to an acceptor, in which a pyrene derivative of general formula I is covalently bonded and which serves as the donor and in which a perylene derivative of general formula II is covalently bonded and which serves as the acceptor.
5. An optical oxygen sensor according to claim 1 or 2, wherein the pyrene or perylene derivative is present in a concentration of 10-4 to 10-2 mol/litre.
6. A silicon matrix according to claim 3 or 4, wherein the pyrene or perylene derivative is present in a concentration of 10-4 to 10-2 mol/litre.
7. An optical oxygen sensor according to claim 1, wherein 1-hydroxymethylpyrene, 1-(11-hydroxyundecyl)-pyrene, 1-(11-hydroxyundecyloxymethyl)pyrene or 1-(2--aminoethyloxymethyl)pyrene is used as the oxygen indicator.
8. An optical oxygen sensor according to claim 2, wherein 1-hydroxymethylpyrene, 1-(11-hydroxyundecyl)-pyrene, 1-(11-hydroxyundecyloxymethyl)pyrene or 1-(2--aminoethyloxymethyl)pyrene is used as the donor and 3-hydroxymethylperylene, 11-amino-1-(3-perylenemethoxy)-undecane, 3-(2-aminoethyloxymethyl)perylene or 3-(11--hydroxyundecyloxymethyl)perylene is used as the acceptor.
9. A silicon matrix according to claim 3, wherein 1-hydroxymethylpyrene, 1-(11-hydroxyundecyl)pyrene, 1-(11--hydroxyundecyloxymethyl)pyrene or 1-(2-aminoethyloxy-methyl)pyrene is used as the oxygen indicator.
10. A silicon matrix according to claim 4, wherein 1-hydroxymethylpyrene, 1-(11-hydroxyundecyl)pyrene, 1-(11--hydroxyundecyloxymethyl)pyrene or 1-(2-aminoethyloxy-methyl)pyrene is used as the donor and 3-hydroxymethyl-perylene, 11-amino-1-(3-perylenemethoxy)undecane, 3-(2--aminoethyloxymethyl)perylene or 3-(11-hydroxyundecyloxy-methyl)perylene is used as the acceptor.
11. Pyrene and perylene derivatives, namely 1-(11--hydroxyundecyl)pyrene, 1-(11-hydroxyundecyloxymethyl)-pyrene, 1-(2-aminoethyloxymethyl)pyrene, 11-amino-1-(3--perylenemethoxy)undecane, 3-(2-aminoethyloxymethyl)-perylene as well as 3-(11-hydroxyundecyloxymethyl)perylene.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH329489 | 1989-09-11 | ||
| CH3294/89 | 1989-09-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2022558A1 true CA2022558A1 (en) | 1991-03-12 |
Family
ID=4252869
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002022558A Abandoned CA2022558A1 (en) | 1989-09-11 | 1990-08-02 | Optical oxygen sensor |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP0417535A3 (en) |
| JP (1) | JPH03118450A (en) |
| CA (1) | CA2022558A1 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19519496A1 (en) * | 1995-05-27 | 1996-11-28 | Lau Matthias Dipl Ing | Oxygen-sensitive single-layer system and method for arranging the system |
| CN101845145B (en) * | 2009-03-26 | 2012-01-11 | 中国科学院化学研究所 | Pyrene substituted polydimethylsiloxane derivative and preparation method and application thereof |
| IN2012DE01687A (en) * | 2012-06-01 | 2015-10-02 | Council Scient Ind Res | |
| DE102017114537A1 (en) | 2017-06-29 | 2019-01-03 | Endress+Hauser Conducta Gmbh+Co. Kg | Sensor membrane, sensor cap and optical sensor |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4476870A (en) * | 1982-03-30 | 1984-10-16 | The United States Of America As Represented By The Department Of Health And Human Services | Fiber optic PO.sbsb.2 probe |
| EP0381026A3 (en) * | 1989-02-03 | 1991-05-02 | F. Hoffmann-La Roche Ag | Optical oxygen sensor |
| EP0447949A1 (en) * | 1990-03-22 | 1991-09-25 | F. Hoffmann-La Roche Ag | Optical oxygen sensor |
-
1990
- 1990-08-02 CA CA002022558A patent/CA2022558A1/en not_active Abandoned
- 1990-08-25 EP EP19900116329 patent/EP0417535A3/en not_active Withdrawn
- 1990-09-10 JP JP2239812A patent/JPH03118450A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JPH03118450A (en) | 1991-05-21 |
| EP0417535A2 (en) | 1991-03-20 |
| EP0417535A3 (en) | 1992-03-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4746751A (en) | Silicone reactive/fluorescent silane dye compositions | |
| US7045361B2 (en) | Analyte sensing via acridine-based boronate biosensors | |
| US5248782A (en) | Long wavelength heteroaryl-substituted dipyrrometheneboron difluoride dyes | |
| Kolmakov et al. | Masked red-emitting carbopyronine dyes with photosensitive 2-diazo-1-indanone caging group | |
| US8344158B2 (en) | Fluorescent polymethine cyanine dyes | |
| EP2036953A2 (en) | Long wavelength thiol-reactive fluorophores | |
| JP6874825B2 (en) | Compounds and color conversion films containing them | |
| US6124135A (en) | Method of determining an alkali ion | |
| CA2022558A1 (en) | Optical oxygen sensor | |
| US8063200B2 (en) | Labeled compound and detection method using the same | |
| JP2002523783A (en) | Energy transfer dye | |
| CA2009024A1 (en) | Optical oxygen sensor | |
| WO1999038919A1 (en) | Fluorescent dye | |
| EP2157088A1 (en) | Indicyanine dyes and the derivatives thereof for analysing biological micromolecules | |
| Trupp et al. | Novel pH indicator dyes for array preparation via NHS ester activation or solid-phase organic synthesis | |
| JP6805464B2 (en) | Compounds and color conversion films containing them | |
| EP2450355B1 (en) | Mercaptofunctional high uB EO chromophores and high tg, low optical loss, covalently bonded, high uB EO chromophore containing polymers and methods of synthesizing EO materials | |
| KR20110033763A (en) | Benz indocyanine compounds for labeling substances, intermediates for the preparation thereof and methods for the preparation thereof | |
| JPH04221745A (en) | Optical oxygen sensor | |
| JP6896970B2 (en) | Nitrogen-containing compounds, color conversion films containing them, and backlight units and display devices containing them. | |
| Dejouy et al. | Synthetic routes to novel fluorogenic pyronins and silicon analogs with far-red spectral properties and enhanced aqueous stability | |
| CN115651641B (en) | Water vapor fluorescence sensor and preparation method thereof | |
| JPH05223737A (en) | Sensor and method of detection | |
| AU662169B2 (en) | Exciplex-based sensors and methods for sensing | |
| Sun et al. | Supporting Information Biomarkers for Phenol Carcinogen Exposure Act as pH-Sensing Fluorescent Probes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |