CN109324102A - A kind of preparation method of diphenhydramine molecular imprinting electrochemical sensor - Google Patents

Abstract

The invention discloses a kind of preparation methods of diphenhydramine molecular imprinting electrochemical sensor, using diphenhydramine as template molecule, pachymic acid is function monomer, azodiisobutyronitrile is initiator, nickel zinc stratiform powder composite material is dopant, it is sensing film modifier with 4- hexamethylene alkoxy -4'- cyanobiphenyl, using oleuropein as crosslinking agent, it is prepared for high sensitivity accordingly, the diphenhydramine molecular imprinting electrochemical sensor of the nickel zinc stratiform powder composite material doping of resistance to falling property, the analysis method is simple and practical, it is complicated to overcome previous analysis method, equipment is expensive, the low disadvantage of sensitivity.

Description

A kind of preparation method of diphenhydramine molecular imprinting electrochemical sensor

Technical field

The present invention relates to molecular imprinting electrochemical sensor, especially a kind of diphenhydramine molecular imprinting electrochemical sensor Preparation method.

Background technique

Diphenhydramine (Diphenhydramine) is a kind of antihistamine.Have the function of antihistaminicum H1 receptor, it is right Nervous centralis has stronger inhibiting effect, and there are also atropine-like effects, is applicable in mucocutaneous anaphylactia, as nettle rash, Hay fever, allergic rhinitis etc., there are also calm, syngignoscisms, it may also be used for the motion sickness such as pre- Anti-seasickness, carsickness, air sickness.But It is long-term or be excessively used such drug will cause to dysuria caused by medicaments insensitive or urodynia, dizziness, the pharyngeal drying of mouth and nose, The side effects such as epigastric discomfort or stomachache, renal failure and liver damage, therefore control medicine is classified as by most of country in the world Object.

The method of measurement diphenhydramine has high performance liquid chromatography, gas chromatography, application of gas chromatorgraphy/mass method etc..However these sides The disadvantages of instrument and equipment of the method due to needing valuableness, there are at high cost, time-consuming, sensitivity is not high.Therefore, a kind of Gao Ling is studied Degree, easy diphenhydramine measuring method has very important significance.

Molecular imprinting technology will be led to functional monomer complementary in structure using object to be measured molecule as template molecule Cross covalently or non-covalently key and form monomer template molecular complex in conjunction with template molecule, add crosslinking agent be allowed to and monomer into Row polymerization reaction forms template molecule polymer, after the reaction was completed by either physically or chemically removing template molecule, is divided Sub- imprinted polymer forms sky complementary and with Multiple recognition site with former microsphere space structure in the polymer Cave.Current method is crosslinked film toughness and rigidity since the function monomer of selection cannot be properly matched with template molecule Also poor, therefore sensitivity is not high and resistance to falling property is bad.

Summary of the invention

The purpose of the present invention is prepare a kind of diphenhydramine molecular imprinting electrochemical sensing of highly sensitive and high crash resistance Device.

In order to reach the purpose of the present invention, simple, production letter that the technical problem to be solved in the present invention is to provide a kind of equipment Easily, the large specific surface area of sensing membrane, electron transmission speed is fast and the diphenhydramine molecular imprinting electrochemical sensor of high-flexibility Preparation method.

In order to solve the above technical problems, the present invention adopts the following technical scheme: using diphenhydramine as template molecule, pachymic acid It is initiator for function monomer, azodiisobutyronitrile, nickel zinc stratiform powder composite material is dopant, 4- hexamethylene alkoxy -4'- Cyanobiphenyl is sensing film modifier, is prepared by crosslinking agent of oleuropein.

A kind of preparation method of above-mentioned diphenhydramine molecular imprinting electrochemical sensor, using diphenhydramine as template molecule, Pachymic acid is function monomer, azodiisobutyronitrile is initiator, using oleuropein as crosslinking agent, nickel zinc stratiform powder composite material It is sensing film modifier for dopant, 4- hexamethylene alkoxy -4'- cyanobiphenyl, is formed in 2 mm glassy carbon electrode surface of diameter Then a kind of hydridization nickel zinc stratiform powder composite material diphenhydramine molecular imprinting polymer membrane uses eluant, eluent molar ratio 4: 1 acetic acid and isobutanol mixed solvent by template molecule elution to get.

A kind of preparation method of above-mentioned diphenhydramine molecular imprinting electrochemical sensor, comprising the following steps:

<1>taking water as a solvent and preparing 20 mL concentration is that the nickel sulfate of 0.25 mol/L, 0.25 mol/L zinc sulfate and concentration are The ascorbic mixed aqueous solution of 0.5 mol/L is that 0.05 mol/L pentaerythrite two is sub- by solvent compound concentration of benzyl alcohol 5 mL of di(2-ethylhexyl)phosphate stearyl, then by 5 mL pentaerythrite diphosphorous acid distearyl ester solutions of preparation with 5 drops/sec of speed Degree be added drop-wise in 20 mL nickel sulfates, zinc sulfate and the vitamin C mixed solution of above-mentioned preparation, during dropwise addition with 2500 turns/ Component velocity is vigorously stirred, then carries out reaction 2 hours at 120 DEG C in the hot water kettle of 50 mL, is collected by centrifugation after cooling resulting Precipitating, using dehydrated alcohol wash 3 times, precipitating is collected by centrifugation, by collection be deposited at 50 DEG C be dried in vacuo to get To nickel zinc stratiform powder composite material；

<2>into 10.0 mL etoh solvents, the mmol template molecule of 1.0 mmol~3.5 diphenhydramine, 2.0 are sequentially added The mmol function monomer of mmol~6.5 pachymic acid, 3.0 mmol crosslinking agent oleuropeins, 0.2 mmol initiator azo two are different The nickel zinc stratiform powder composite material of the g of 0.0050 g~0.0150 prepared by butyronitrile, step<1>and the 4- hexamethylene of 0.030 g Alkoxy -4'- cyanobiphenyl senses film modifier, every to be added a kind of the dissolution of chemical reagent ultrasonic wave 8 minutes；

<3>taking the 8 μ L of mixture of step<2>to be applied to clean smooth diameter is that it is small to place 6 in the glassy carbon electrode surface of 2 mm Electrode after modification is placed in 80 DEG C of vacuum oven thermal polymerization 2.0 hours, then uses eluant, eluent molar ratio by Shi Hou For 4:1 acetic acid and isobutanol mixed solvent by template molecule elution to get.

The study found that be function monomer using diphenhydramine as template molecule, pachymic acid, azodiisobutyronitrile is initiator, Nickel zinc stratiform powder composite material is dopant, 4- hexamethylene alkoxy -4'- cyanobiphenyl is sensing film modifier, with olive hardship Glycosides is the diphenhydramine molecular imprinting electrochemical sensor of crosslinking agent preparation, can be used for measuring the content of diphenhydramine.Using this The electrochemical analysis method of measurement diphenhydramine is established in invention, has very outstanding sensitivity；The concentration of diphenhydramine 1.0 × 10^-8 ~ 2.3×10^-4Good linear relationship (linearly dependent coefficient is R=0.9989), detection are presented within the scope of mol/L Limit (S/NIt=3) is 2.2 × 10^-9Mol/L, therefore, nickel zinc stratiform powder composite material adulterates and 4- hexamethylene alkoxy -4'- The modified diphenhydramine molecular imprinting electrochemical sensor sensitivity with higher of cyanobiphenyl, more than current detection side Method；In addition, drop test finds that the sensor still has preferable repeatability during measuring diphenhydramine, because of a little biographies Sensor has preferable crash resistance；And equipment is simple, production is simple.

Detailed description of the invention

Fig. 1 is a kind of working curve diagram of the preparation method of diphenhydramine molecular imprinting electrochemical sensor in embodiment 1.

Specific embodiment

Embodiment 1

One, the processing of glass-carbon electrode

Glass-carbon electrode is successively polished with 1.0 μm, 0.3 μm and 0.05 μm of alumina powder on polishing cloth, is then placed in body Product ratio is 8 min of ultrasound in the nitric acid of 1:1, places into 8 min of ultrasound in dehydrated alcohol, is finally cleaned by ultrasonic with pure water clean.

Two, the preparation of diphenhydramine molecular imprinting electrochemical sensor

<1>taking water as a solvent and preparing 20 mL concentration is that the nickel sulfate of 0.25 mol/L, 0.25 mol/L zinc sulfate and concentration are The ascorbic mixed aqueous solution of 0.5 mol/L is that 0.05 mol/L pentaerythrite two is sub- by solvent compound concentration of benzyl alcohol 5 mL of di(2-ethylhexyl)phosphate stearyl, then by 5 mL pentaerythrite diphosphorous acid distearyl ester solutions of preparation with 5 drops/sec of speed Degree be added drop-wise in 20 mL nickel sulfates, zinc sulfate and the vitamin C mixed solution of above-mentioned preparation, during dropwise addition with 2500 turns/ Component velocity is vigorously stirred, then carries out reaction 2 hours at 120 DEG C in the hot water kettle of 50 mL, is collected by centrifugation after cooling resulting Precipitating, using dehydrated alcohol wash 3 times, precipitating is collected by centrifugation, by collection be deposited at 50 DEG C be dried in vacuo to get To nickel zinc stratiform powder composite material；

<2>into 10.0 mL etoh solvents, the mmol template molecule of 1.0 mmol~3.5 diphenhydramine, 2.0 are sequentially added The mmol function monomer of mmol~6.5 pachymic acid, 3.0 mmol crosslinking agent oleuropeins, 0.2 mmol initiator azo two are different The nickel zinc stratiform powder composite material of the g of 0.0050 g~0.0150 prepared by butyronitrile, step<1>and the 4- hexamethylene of 0.030 g Alkoxy -4'- cyanobiphenyl senses film modifier, every to be added a kind of the dissolution of chemical reagent ultrasonic wave 8 minutes；

<3>taking the 8 μ L of mixture of step<2>to be applied to clean smooth diameter is that it is small to place 6 in the glassy carbon electrode surface of 2 mm Electrode after modification is placed in 80 DEG C of vacuum oven thermal polymerization 2.0 hours, then uses eluant, eluent molar ratio by Shi Hou For 4:1 acetic acid and isobutanol mixed solvent by template molecule elution, by magnetic agitation eluted template molecule, until eluent In can't detect template molecule, then wash away the solvent of trace electrode surface with ultrapure water, be then stored in trace electrode ultrapure It is stand-by in water.

Three, the drafting of working curve, the measurement of detection limit

The experiment of molecular engram electrode response characteristic is carried out using differential pulse voltammetry, measures the range of linearity and detection limit.It will Diphenhydramine molecular engram electricity that nickel zinc stratiform powder composite material adulterates and that 4- hexamethylene alkoxy -4'- cyanobiphenyl is modified Pole cultivates 6 minutes in the diphenhydramine of various concentration respectively, and (bottom liquid is 5.0 mmol/L K₃[Fe(CN)₆]-0.5 The phosphate buffer solution solution of pH=7.5 mol/L), then carry out differential pulse voltammetry measurement.Diphenhydramine is dense Degree is 1.0 × 10^-8 ~ 2.3×10^-4Good linear relationship is presented within the scope of mol/L；Linear equation isIp(μA) = - 0.0949 с (μm ol/L)+23.05, linearly dependent coefficient be R=0.9989, detection limit (S/NIt=3) is 2.2 × 10^-9 mol/L。

Four, diphenhydramine molecular imprinting electrochemical sensor crash resistance is tested

Diphenhydramine that the nickel zinc stratiform powder composite material of preparation adulterates and that 4- hexamethylene alkoxy -4'- cyanobiphenyl is modified Molecular engram sensor first carries out falling 5 times on 1.5 meters of high experimental benches, fall every time be all made of differential pulse voltammetry into The experiment of row molecular engram electrode response characteristic, the repetitive rate of the concentration of 5 measurement diphenhydramines is between 95%-98%.

Therefore, benzene sea which adulterates and that 4- hexamethylene alkoxy -4'- cyanobiphenyl is modified Lamine molecular engram electrode has high sensitivity and crash resistance with higher.

Claims (1)

1. a kind of preparation method of diphenhydramine molecular imprinting electrochemical sensor, it is characterised in that with 0.10 mmol/mL~ The diphenhydramine of 0.35 mmol/mL be template molecule, the mmol/mL of 0.20 mmol/mL~0.65 pachymic acid be function list Body, 0.02 mmol/mL azodiisobutyronitrile be initiator, using the oleuropein of 0.30 mmol/mL as crosslinking agent, 0.0005 The nickel zinc stratiform powder composite material of the g/mL of g/mL~0.0015 is the 4- hexamethylene alkoxy-of dopant, 0.0030 g/mL 4'- cyanobiphenyl is sensing film modifier, forms a kind of hydridization nickel zinc stratiform powder composite material in glassy carbon electrode surface and mixes Then miscellaneous diphenhydramine molecular imprinting polymer membrane uses eluant, eluent acetic acid and isobutanol mixed solvent eluted template molecule To obtain the final product；

Specifically carried out by following operation:

<1>taking water as a solvent and preparing 20 mL concentration is that the nickel sulfate of 0.25 mol/L, 0.25 mol/L zinc sulfate and concentration are The ascorbic mixed aqueous solution of 0.5 mol/L is that 0.05 mol/L pentaerythrite two is sub- by solvent compound concentration of benzyl alcohol 5 mL of di(2-ethylhexyl)phosphate stearyl, then by 5 mL pentaerythrite diphosphorous acid distearyl ester solutions of preparation with 5 drops/sec of speed Degree be added drop-wise in 20 mL nickel sulfates, zinc sulfate and the vitamin C mixed solution of above-mentioned preparation, during dropwise addition with 2500 turns/ Component velocity is vigorously stirred, then carries out reaction 2 hours at 120 DEG C in the hot water kettle of 50 mL, is collected by centrifugation after cooling resulting Precipitating, using dehydrated alcohol wash 3 times, precipitating is collected by centrifugation, by collection be deposited at 50 DEG C be dried in vacuo to get To nickel zinc stratiform powder composite material；

<2>into 10.0 mL etoh solvents, the mmol template molecule of 1.0 mmol~3.5 diphenhydramine, 2.0 are sequentially added The mmol function monomer of mmol~6.5 pachymic acid, 3.0 mmol crosslinking agent oleuropeins, 0.2 mmol initiator azo two are different The nickel zinc stratiform powder composite material of the g of 0.0050 g~0.0150 prepared by butyronitrile, step<1>and the 4- hexamethylene of 0.030 g Alkoxy -4'- cyanobiphenyl senses film modifier, every to be added a kind of the dissolution of chemical reagent ultrasonic wave 8 minutes；

<3>taking the 8 μ L of mixture of step<2>to be applied to clean smooth diameter is that it is small to place 6 in the glassy carbon electrode surface of 2 mm Electrode after modification is placed in 80 DEG C of vacuum oven thermal polymerization 2.0 hours, then uses eluant, eluent molar ratio by Shi Hou For 4:1 acetic acid and isobutanol mixed solvent by template molecule elution to get.