Comunicacion oral eseac_2010

DIFFERENTIAL POTENTIOMETRY AND DIFFERENTIAL POTENTIOMETRY AND DIFFERENTIAL DYNAMIC RESPONSE WITH IONDIFFERENTIAL DYNAMIC RESPONSE WITH ION

SELECTIVE ELECTRODES: APPLICATION TO SELECTIVE ELECTRODES: APPLICATION TO CYCLODEXTRINE-BASED DRUG SELECTIVECYCLODEXTRINE-BASED DRUG SELECTIVE

ELECTRODESELECTRODES

María CuarteroMaría Cuartero, Joaquín A. Ortuño and MªSoledad García

MÉTODOS AUTOMÁTICOS DE ANÁLISIS. SENSORES QUÍMICOS

“AUTOMATIC METHODS OF ANALYSIS. CHEMICAL SENSORS”

Department of Analytical Chemistry. Faculty of Chemistry

University of Murcia. Murcia. Spain

PLASTICIZED POLYMERIC MEMBRANES

ION-SELECTIVE ELECTRODESION-SELECTIVE ELECTRODES

ISEsISEsSelectivity

Sensitivity

Simplicity Rapid response

Longterm stability

Wide linear range

Low cost

Applications

PVCPlasticizer

Ionic additiveIonophore

The appropriate selection of the components enables the selectivity of the ISE to be controlled.

Dynamic response Dynamic response studiesstudies

(E vs t)

Response time of the sensor

Working mechanism

Practical applications

Interfering ions

Data matrix (E and t)

Qualitative and quantitative purposes

important

particulary relevant

exploited

electrode 1

reference electrode

electrode 2

SOFTWARETWO-ELECTRODE POTENTIOMETRY

ELECTRODE 1

ELECTRODE 2

REFERENCE ELECTRODE

High impedance buffers

Analogmultiplexer

A/D converter16 bits+

-

Reference voltage2.5 V

Digital control

Controller

USB interface

PC

ELECTRODE 1

ELECTRODE 2

REFERENCE ELECTRODE

High impedance buffers

Analogmultiplexer

A/D converter16 bits+

-

Reference voltage2.5 V

Digital control

Controller

USB interface

PC

The potential difference between two ISEs are alternatively measured by means of two analog circuits, a fast multiplexer and an analog-to digital converter. The potential difference between both ISEs is obtained by digital substraction of the previous recording.

This procedure has the advantage that not only is the potential difference between two ISEs monitored but also the potential of each electode.

Two-electrode potentiometryTwo-electrode potentiometry



Electrode 1

Electrode 2


Electrode 1

Electrode 2

DIFFERENTIAL DYNAMIC RES PONS E (DDR)DIFFERENTIAL DYNAMIC RES PONS E (DDR)

Two-electrodes potentiometryTwo-electrodes potentiometry

Electrode 1

Electrode 2

DIFFERENTIAL DYNAMIC RES PONS E (DDR)DIFFERENTIAL DYNAMIC RES PONS E (DDR)

DIFFERENTIAL DIFFERENTIAL POTENTIOMETRY (DP)POTENTIOMETRY (DP)

The potential d iffe re nce be twe e n both

e le ctrod e s once that the s te ad y-state value has

be e n attaine d

Overall potential response

E (ΔGo, βCD-drug, …)

The direct transfer of the ionic drug from water to the

plasticizer is favourable.

Formation constant of complexes between CD and drug are not very

high.

OR''

O

H

ORH

O

n

R'O

n=6 α-CD

n=7 β-CD

n=8 γ-CD

alkylated cyclodextrin-based drug selective electrodes



The direct transfer of the ionic drug from water to the

plasticizer is favourable.

Formation constant of complexes between CD and drug are not very

high.

benzoyl beta-cyclodextrin derivative

AntiarrhytmicAntiarrhytmic

N

N

O

HO

H

H

H2N

O

N

Procainamide

Quinidine

AntimalarialAntimalarial

N

N

HO

O

H

H

Quinine

AntidepressantAntidepressant

N

N

Clomipramine



The direct transfer water-plasticizer is very favourable

Not very high


AnesthesicsAnesthesics

HN

N

O

BupivacaineHN N

O

Lidocaine

H2N

O

N

O

Procaine

NH

O

N

O

TetracaineN

O

O

O

O

Papaverine




Not very high

AntispasmodicAntispasmodic



HN

N

O

BupivacaineHN N

O

Lidocaine

H2N

O

N

O

Procaine

NH

O

N

O

TetracaineN

O

O

O

O

Papaverine



lipophilic aromatic ring system and a nitrogen that can be protonated to provide

a cationic drug




Not very high


E (ΔGo, βCD-drug, βCD-plasticizer…)


Not very high

Neutral, lipophilic CDs manifest recognition by three types of interactions:

conventional hydrophobic bonding

-N-H…O and N-C-H…O hydrogen bonding

van der Waals’ forces.


HN

N

O

BupivacaineHN N

O

Lidocaine

H2N

O

N

O

Procaine

NH

O

N

O

TetracaineN

O

O

O

O

Papaverine



lipophilic aromatic ring system and a nitrogen that can be protonated to provide

a cationic drug

ELECTRODE 1ELECTRODE 1

MembraneMembrane:

100 mg Polyvinyl chloride (PVCPVC) 30%30%

200 mg PlasticizerPlasticizer 60%60%

30 mg Heptakis(2,3,5-tri-O-benzoyl)-β-cyclodextrin (β-CDβ-CD) 9%9%

3 mg tetrakis[3,5-bis-(trifluoromethyl)phenyl]borate (TFMPBTFMPB) 1%1%

ELECTRODE 2ELECTRODE 2

Blank Membrane:Blank Membrane:

100 mg PVCPVC 33%33%

200 mg PlasticizerPlasticizer 66%66%

3 mg TFMPBTFMPB 1%1%


E (ΔGo, βCD-drug, βCD-plasticizer…)


Not very high

Neutral, lipophilic CDs manifest recognition by three types of interactions:

conventional hydrophobic bonding

-N-H…O and N-C-H…O hydrogen bonding

van der Waals’ forces.


MEMBRANES ASSAYEDMembranes DOS NPOE TCP FNDPE PVC TFMB Β-CD

A - - - 66 33 1 -

B - - - 60 30 1 9

C - - 66 - 33 1 -

D - - 60 - 30 1 9

E - 66 - - 33 1 -

F - 60 - - 30 1 9

G 66 - - - 33 1 -

H 60 - - - 30 1 9

dioctyl sebacate (DOS), 2-nitrophenyl octyl ether (NPOE), tricresyl phosphate (TCP), 2-fluoro-2’-nitrodiphenyl ether (FNDPE), polyvinyl chloride (PVC) , potassium tetrakis[3,5-bis-(trifluoromethyl)phenyl]borate (TFMB) and

Heptakis(2,3,5-tri-O-benzoyl)-β-cyclodextrin (β-CD)


A - - - 66 33 1 -

B - - - 60 30 1 9

C - - 66 - 33 1 -

D - - 60 - 30 1 9

E - 66 - - 33 1 -

F - 60 - - 30 1 9

G 66 - - - 33 1 -

H 60 - - - 30 1 9



H2O

Ag-AgCl│KCl (1x10-4 M)│internal solution, 1x10-4 M KCl│PVC membrane│sample solution

Reproducible initial stage The electrodes were conditioned in deionized

water until they reached a constant potential


A - - - 66 33 1 -

B - - - 60 30 1 9

C - - 66 - 33 1 -

D - - 60 - 30 1 9

E - 66 - - 33 1 -

F - 60 - - 30 1 9

G 66 - - - 33 1 -

H 60 - - - 30 1 9



Ag-AgCl│KCl (1x10-4 M)│internal solution, 1x10-4 M KCl│PVC membrane│sample solution

Reproducible initial stageA flux of potassium ions from the inner solution

to the sample solution is established until a steady-state concentration profile inside the

membrane is reached, which is manifested as a CONSTANT ELECTRODE POTENTIALCONSTANT ELECTRODE POTENTIAL

Concentration perturbation (Input)Concentration perturbation (Input)

Standard addition methodStandard addition method

Adding consecutive volumes of concentrated solution of the

different drugs


time

log C


time

log C


time

log C

The duration of each step depended on the electrode response observed and, in general, decreased as the

concentration was increased.

SAMPLE SOLUTION

ION-SELECTIVE MEBRANE INTERNAL SOLUTION

δaq δm

aK

[CD-K]

[CD-J]

aDaK(bulk)

aJ(bulk)

CONCENTRATION PROFILESCONCENTRATION PROFILES

K= potassium

J= ionic drug

CD= cyclodextrin

δ= diffusion layer

during exposure to the corresponding ionic drug, a flux towards the filling solution is established, coupled to a

flux of potassium in the opposite direction

MEMBRANEMEMBRANE INTERNAL S OLUTION INTERNAL S OLUTION S AMPLE S OLUTIONS AMPLE S OLUTION

K+

K+

K+

K+

K+

KCl 10KCl 10-4-4 M M

K+

K+

K+

J+

J+

J+

J+

J+

J+

J+

J+ J+

K+K+

J+

CD

t / s

0 1000 2000 3000 4000

E1-

E2 /

mV

0

50

100

150

200

250

t / s0 1000 2000 3000

E1-E

2 / m

V

0

10

20

30

40

50

60

t / s0 500 1000 1500 2000

E1-E

2 /

mV

-50

0

50

100

150

200

250

t / s0 200 400 600 800 1000 1200 1400 1600 1800

E1-E

2 /

mV

-50

0

50

100

150

200

250

DOS TCP

NPOE FNDPE

1

2

3

4

56

7 8

1

2

3

4

5

6

8

1

2

3

4

5 6 8

1 2

3

4

56

8

7

7

7

DDR of lidocaine (different plasticizers)DDR of lidocaine (different plasticizers)

(1) 0 M, (2) 1x10-6 M, (3) 5x10-6 M, (4) 1x10-5 M, (5) 5x10-5 M, (6) 1x10-4 M, (7) 5x10-4 M, (8) 1x10-3 M

t / s

0 1000 2000 3000 4000

E1-

E2

/ m

V

0

50

100

150

200

250

t / s0 1000 2000 3000

E1-E

2 / m

V

0

10

20

30

40

50

60

t / s0 500 1000 1500 2000

E1-

E2

/ m

V

-50

0

50

100

150

200

250

t / s

0 200 400 600 800 1000 1200 1400 1600 1800

E1-E

2 / m

V

-50

0

50

100

150

200

250

DOS TCP

NPOE FNDPE

1

2

3

4

56

7 8

1

2

3

4

5

6

8

1

2

3

4

5 6 8

1 2

3

4

56

8

7

7

7


t / s

0 1000 2000 3000 4000

E1-

E2

/ m

V

0

50

100

150

200

250

t / s0 1000 2000 3000

E1-E

2 / m

V

0

10

20

30

40

50

60

t / s0 500 1000 1500 2000

E1-

E2

/ m

V

-50

0

50

100

150

200

250

t / s

0 200 400 600 800 1000 1200 1400 1600 1800

E1-E

2 / m

V

-50

0

50

100

150

200

250

DOS TCP

NPOE FNDPE

1

2

3

4

56

7 8

1

2

3

4

5

6

8

1

2

3

4

5 6 8

1 2

3

4

56

8

7

7

7



The lidocaine concentration at which this inversion occured

depend on the plasticizer used. For

DOS, NPOE and FNDPE increased with the dielectric constant

(ε=4, 24 and 50 respectively).

The potential corresponding to the

inversion was roughly the same for these three plasticizers.

t / s

0 1000 2000 3000 4000

E1-

E2

/ m

V

0

50

100

150

200

250

t / s0 1000 2000 3000

E1-E

2 / m

V

0

10

20

30

40

50

60

t / s0 500 1000 1500 2000

E1-

E2

/ m

V

-50

0

50

100

150

200

250

t / s

0 200 400 600 800 1000 1200 1400 1600 1800

E1-E

2 / m

V

-50

0

50

100

150

200

250

DOS TCP

NPOE FNDPE

1

2

3

4

56

7 8

1

2

3

4

5

6

8

1

2

3

4

5 6 8

1 2

3

4

56

8

7

7

7


t / s

0 1000 2000 3000 4000

E1-

E2

/ m

V

0

50

100

150

200

250

t / s0 1000 2000 3000

E1-E

2 / m

V

0

10

20

30

40

50

60

t / s0 500 1000 1500 2000

E1-

E2

/ m

V

-50

0

50

100

150

200

250

t / s

0 200 400 600 800 1000 1200 1400 1600 1800

E1-E

2 / m

V

-50

0

50

100

150

200

250

DOS TCP

NPOE FNDPE

1

2

3

4

56

7 8

1

2

3

4

5

6

8

1

2

3

4

5 6 8

1 2

3

4

56

8

7

7

7



One drawback of the membranes

constructed with DOS, NPOE and FNDPE, is that the response is

not reproducible because the membrane can not be regenerated

after a concentration perturbation.

DOS, NPOE and FNDPE none reproducible

TCP reproducible

t / s

0 1000 2000 3000 4000

E1-

E2

/ m

V

0

50

100

150

200

250

t / s0 1000 2000 3000

E1-E

2 / m

V

0

10

20

30

40

50

60

t / s0 500 1000 1500 2000

E1-

E2

/ m

V

-50

0

50

100

150

200

250

t / s

0 200 400 600 800 1000 1200 1400 1600 1800

E1-E

2 / m

V

-50

0

50

100

150

200

250

DOS TCP

NPOE FNDPE

1

2

3

4

56

7 8

1

2

3

4

5

6

8

1

2

3

4

5 6 8

1 2

3

4

56

8

7

7

7


t / s

0 1000 2000 3000 4000

E1-

E2

/ m

V

0

50

100

150

200

250

t / s0 1000 2000 3000

E1-E

2 / m

V

0

10

20

30

40

50

60

t / s0 500 1000 1500 2000

E1-

E2

/ m

V

-50

0

50

100

150

200

250

t / s

0 200 400 600 800 1000 1200 1400 1600 1800

E1-E

2 / m

V

-50

0

50

100

150

200

250

DOS TCP

NPOE FNDPE

1

2

3

4

56

7 8

1

2

3

4

5

6

8

1

2

3

4

5 6 8

1 2

3

4

56

8

7

7

7



In contrast, the membrane constructed with TCP displayed a much lower potential

respose but its response was reproducible.

The different behaviour displayed by TCP can

be explained from some results reported

in the literature that point to an interaction

between TCP and protonated amines.

DOS, NPOE and FNDPE none reproducible

TCP reproducible

DP of lidocaine (different plasticizers)DP of lidocaine (different plasticizers)

log [L] / M

-6 -5 -4 -3

mV

-50

0

50

100

150

200

250

DOS TCP NPOE

FNDPE

Plots of DP versus logarithmic concentration of lidocaine

The response of the electrode containing CD is higher than the response of the electrode without CD at low concentration,

while the response is more similar at higher

concentrations.

t / s0 1000 2000 3000

E1-E

2 /

mV

0

10

20

30

40

50

60

t / s

0 1000 2000 3000

E1-

E2 /

mV

0

20

40

60

80

100

t / s

0 500 1000 1500 2000 2500 3000

E1-E

2 /

mV

0

10

20

30

40

50

60

t / s

0 1000 2000 3000 4000

E1-E

2 /

mV

-20

-10

0

10

20

30

40

DDR of different ionic drugs (membranes with TCP)DDR of different ionic drugs (membranes with TCP)


LIDOCAINE

CLORMIPRAMINEPAPAVERINE

PROCAINE

81

2

3

4

5 6 7

81

2

3

4

576

81

2

3

4

657

1

2

3

4

6 85 7

t / s0 1000 2000 3000

E1-E

2 /

mV

0

10

20

30

40

50

60

t / s

0 1000 2000 3000E

1-E

2 /

mV

0

20

40

60

80

100

t / s

0 500 1000 1500 2000 2500 3000

E1-

E2 /

mV

0

10

20

30

40

50

60

t / s

0 1000 2000 3000 4000

E1-E

2 /

mV

-20

-10

0

10

20

30

40


LIDOCAINE


PROCAINE

81

2

3

4

5 6 7

81

2

3

4

576

81

2

3

4

657

1

2

3

4

6 85 7

t / s0 1000 2000 3000

E1-E

2 /

mV

0

10

20

30

40

50

60

t / s

0 1000 2000 3000E

1-E

2 /

mV

0

20

40

60

80

100

t / s

0 500 1000 1500 2000 2500 3000

E1-

E2 /

mV

0

10

20

30

40

50

60

t / s

0 1000 2000 3000 4000

E1-E

2 /

mV

-20

-10

0

10

20

30

40

t / s0 1000 2000 3000

E1-E

2 /

mV

0

10

20

30

40

50

60

t / s

0 1000 2000 3000E

1-E

2 /

mV

0

20

40

60

80

100

t / s

0 500 1000 1500 2000 2500 3000

E1-

E2 /

mV

0

10

20

30

40

50

60

t / s

0 1000 2000 3000 4000

E1-E

2 /

mV

-20

-10

0

10

20

30

40


LIDOCAINE


PROCAINE

81

2

3

4

5 6 7

81

2

3

4

576

81

2

3

4

657

1

2

3

4

6 85 7


The more lipophilic the ionic drug (clomipramine>papaverine>lidocaine>procaine), the lower the inversion

concentration and the higher the inversion potential

t / s0 1000 2000 3000

E1-E

2 /

mV

0

10

20

30

40

50

60

t / s

0 1000 2000 3000E

1-E

2 /

mV

0

20

40

60

80

100

t / s

0 500 1000 1500 2000 2500 3000

E1-

E2 /

mV

0

10

20

30

40

50

60

t / s

0 1000 2000 3000 4000

E1-E

2 /

mV

-20

-10

0

10

20

30

40


LIDOCAINE


PROCAINE

81

2

3

4

5 6 7

81

2

3

4

576

81

2

3

4

657

1

2

3

4

6 85 7

t / s0 1000 2000 3000

E1-E

2 /

mV

0

10

20

30

40

50

60

t / s

0 1000 2000 3000E

1-E

2 /

mV

0

20

40

60

80

100

t / s

0 500 1000 1500 2000 2500 3000

E1-

E2 /

mV

0

10

20

30

40

50

60

t / s

0 1000 2000 3000 4000

E1-E

2 /

mV

-20

-10

0

10

20

30

40

t / s0 1000 2000 3000

E1-E

2 /

mV

0

10

20

30

40

50

60

t / s

0 1000 2000 3000E

1-E

2 /

mV

0

20

40

60

80

100

t / s

0 500 1000 1500 2000 2500 3000

E1-

E2 /

mV

0

10

20

30

40

50

60

t / s

0 1000 2000 3000 4000

E1-E

2 /

mV

-20

-10

0

10

20

30

40


LIDOCAINE


PROCAINE

81

2

3

4

5 6 7

81

2

3

4

576

81

2

3

4

657

1

2

3

4

6 85 7


The different DDR obtained for all the drugs assayed could well be used for qualitative purposes

DP (membranes with TCP)DP (membranes with TCP)

log [C] / M

-10 -8 -6 -4 -2

mV

0

20

40

60

80Na+

K+

Mg2+

Ca2+

NH4

+

TEA ProcainamideProcaineLidocaineTetracaineBupivacaineQuinidina

QuininaPapaverineClormipramine

Plots of DP versus logarithmic concentration of the different compounds assayed

Perturbation of concentrationPerturbation of concentrationConcentration perturbation (Input)Concentration perturbation (Input)

time

log C

The electrode is re-conditioned in deionised

water after each concentration perturbation


time

log C

The electrode is re-conditioned in deionised

water after each concentration perturbation

t / s (1div=50 s)

E1-

E2

/ mV

(1d

iv=

20m

V)

E1-

E2

/ mV

(1

div

=5

mV

)

t / s (1div=20 s)

E1-

E2

/ m

V (

1d

iv=

20m

V)

DDR of lidocaine (membranes with TCP)DDR of lidocaine (membranes with TCP)

1x10-6 M 5x10-6 M 1x10-5 M

5x10-5 M 1x10-4 M 5x10-4 M

log C

time

mV

time

CONCENTRATION PERTURBATION

(INPUT=MONOTONIC)DDR

(OUTPUT=NON-MONOTONIC)


This type of signals has been reported for the dynamic response of several types of ISEs in the presence of interfiring ions.

t / s

0 200 400 600 800 1000 1200 1400 1600

mV

0

50

100

150

200

250

300

5x10-4 M

1x10-4 M

5x10-5 M

1x10-5 M

5x10-6 M

1x10-6 M

electrode 1

electrode 2 (Blank membrane)

t / s

0 200 400 600 800 1000 1200 1400 1600

mV

0

50

100

150

200

250

300

5x10-4 M

1x10-4 M

5x10-5 M

1x10-5 M

5x10-6 M

1x10-6 M

electrode 1


electrode 1



t / s (1div=50 s)

E1-E

2 / mV

(1d

iv=20

mV

)

E1-E

2 / mV

(1d

iv=5

mV

)

t / s (1div=20 s)

E1-E

2 / mV

(1d

iv=20

mV

)

1x10-6 M 5x10-6 M 1x10-5 M

5x10-5 M 1x10-4 M 5x10-4 M

t / s (1div=50 s)

E1-E

2 / mV

(1d

iv=20

mV

)

E1-E

2 / mV

(1d

iv=5

mV

)

t / s (1div=20 s)

E1-E

2 / mV

(1d

iv=20

mV

)

1x10-6 M 5x10-6 M 1x10-5 M

5x10-5 M 1x10-4 M 5x10-4 M

DDR(NON-MONOTONIC)

DR(MONOTONIC)

log [L] / M

-6 -5 -4 -3

mV

-50

0

50

100

150

200

250

E(mV)=724.84+151.44log[L(M)+1.06x10-5]

Calibration graphs for DP and DDR of lidocaine (membranes Calibration graphs for DP and DDR of lidocaine (membranes with TCP)with TCP)

A

B

│A│-│B│

CONVENTIONAL DP

DDR

rather odd signals

two ionic drug trasport inside the membrane

free ionic drug complexed ionic drug

the difussion of CD to the sample interface is insufficient to complex all the ionic drug arising from the

sample solution

lower concentrations higher concentrations

CONCLUSIONSCONCLUSIONS

I. The new differential dynamic response technique, applied to ion-selective electrodes, and exploited here for the first time, is a source of signals not usually seen that can be useful for quantitative an qualitative analysis.

IV.When the DDR is applied to ISEs based on a β-cyclodextrin, the ionic drugs assayed seem to be transported across the membrane following two different processes.

THANK YOU FOR YOUR ATTENTIONTHANK YOU FOR YOUR ATTENTION

Business

Comunicacion oral eseac_2010