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Electrochemical Sensors for Determination of Urea

#3875


Design of Electrochemical Enzyme Free Sensors for Determination of Urea and Other Biogenic Amines

Tech Area / Field

  • MED-DID/Diagnostics & Devices/Medicine
  • BIO-OTH/Other/Biotechnology
  • CHE-ANL/Analytical Chemistry/Chemistry

Status
3 Approved without Funding

Registration date
21.05.2008

Leading Institute
Institute of Organic Synthesis, Russia, Sverdlovsk reg., Ekaterinburg

Supporting institutes

  • Ural State Economic University, Russia, Sverdlovsk reg., Ekaterinburg\nScientific Research Institute of Chemistry and Technology of Organo-Element Compounds, Russia, Moscow

Collaborators

  • Dow Corning Corporation, USA, MI, Midland

Project summary

Modern medicine considers concentrations of urea and uric acid in a blood serum and dialysis liquid as criteria of state of health and hemodyalisis quality. As a source of information on their concentrations the sensors based on metalloenzymes (urease or uricase) are used, which possess the necessary sensitivity to urea or uric acid, but they have low stability and high cost. Besides modern analysis methods require special expensive equipment, and only particular medical centers are equipped with them.

High sensitivity and selectivity, efficiency in getting results, possibility of work in a field conditions, relative simplicity and availability of equipment in electrochemical analytic methods make it possible to propose them for monitoring of human health state. Enzyme free sensors will enable to realize on-site variants of the analyses. Combination of chemical stability with good electric conductivity, large specific surface and high adsorptive ability makes the nanoscale materials (NSM) to be promising transducers.

The main idea of the project is molecular design including also virtual design of synthetic organic receptors on a basis of catalytic systems containing transition metals. Implementation of the project will result in the development of such receptors as organic molecules (including chiral ones) having the electrochemical characteristics comparable to those for natural enzymes.

There will be solved one of the most important problem of supramolecular chemistry i.e. the design of synthetic analogues of enzymes able to selective binding of carbonyl containing biogenic amines, such as amino acids, oligopeptides, urea and uric acid. Utilization of the nanocrystalline transducers developed in this project, immobilization of the synthesized receptors on them reveals prospects for the development of sensors of new generation, necessary for rapid diagnostics of different diseases, efficient monitoring of hemodyalisis processes.

Synthetic section of the project consist of elaboration of methods for introduction of nitrogen containing heterocycles and other ligands to (aza)macroheterocycles and their analogues, as well as to metal complexes of these compounds by means of methodologies of nucleophilic aromatic substitution (addition) or multicomponent condensation. There the systems with any coordination centers able to realize a specified function will be synthesized. Heterocyclic fragment (spacer) will be targeted for interaction with carbonyl group, and metal cation in macroheterocyclic cavity will be targeted for binding of amino group. The latter will allow registering electrochemical response, arising on the metal cation.

Goals of the project:

  1. To develop and synthesize artificial enzymes and metalloenzymes having high substrate specificity to biogenic amines.
  2. To design on their basis a new class of electrochemical enzyme free sensors of biogenic amines (with urea as an example) not is conceding with sensitivity and selectivity of enzyme containing biosensors.
  3. To elaborate the software and methodical coverage for operative monitoring of urea concentration in serum and dialysis liquid using voltammetric IVA-5 analyzer supplied with the above sensors.

Expected results and their applications
  1. New highly sensitive molecular receptors (including chiral ones) of amino acids, oligopeptides, urea, uric acid etc. will be obtained. They will become a basis for development of electrochemical sensors of new generation.
  2. New enzymes free electrochemical sensors for biogenic amines will be elaborated, which will have nanoscale metaloxide or carbon materials as transducer, and functionalized synthetic enzymes as receptor, able for binding a target biogenic amine and catalyzing the processes of its electrochemical oxidation.
  3. New low-cost and easily available analyzer will be created for determination of the concentrations of biogenic amines in serum and dialysis liquid. The basis of the instrument will be the voltammetric analyzer IVA-5 created during the progress of ISTC project 342 and electrochemical enzymes free sensor of urea.

Application field of the project: public health.

The confidence of successful project realizations is provided by:

  1. High professional qualification and wide capabilities of Russian scientists in the field of direct synthesis of element organic compounds (GNIICHTEOS); computational modeling of “substrate-receptor” interaction and targeted synthesis of cation receptors and organic molecules (IOS), designing of electrochemical sensors and measurers (SICST USUE).
  2. Close cooperation of Russian scientists with foreign researchers (collaborators), which have long experience and expert knowledge in the field of organic and coordination chemistry.
  3. Results of preliminary research work:
    • for the first time the introduction of heterocyclic subsistents into crown-ethers, podands, calixarenes and porphyrines by reactions of nucleophilic substitution of hydrogen in azines as well as method of multicomponent condensation has been performed;
    • methods for design of supramolecular coordination compounds of the specified structure have been developed;
    • software for mathematic modeling of interaction between natural metalloenzymes and organic ligands has been developed;
    • electrochemical response proportional to urea concentration has been detected for sensors on a basis of obtained synthetic metalloenzymes


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