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Liquid Column Chromatography with Chemical Derivatizations after Separation. [New analytical methods (15)]

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1231 M . 7: Reetz, Chem. Ber. 110, 954 (1977).
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1975, 2279.
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[35] M . 7: Reetz, unpublished results 1977.
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[37] M . 7: Reetz, N . G r e f , to be published.
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Organomet. Chem. 34, 93 (1972).
[39] E. A . Ebsw'orth in A . G. MacDiarmid. The Bond to Carbon. Vol. I,
Part I, Marcel Dekker, New York 1968, p. 46.
1401 N . G r e g Dissertation, Universitat Marburg 1977.
In the thermal rearrangement of u-silyl ketones to vinyl silyl ethers
the intermediacy of reactive pentacoordinated silicon species is likely:
H . Kwart, W E. Barnette, J. Am. Chem. SOC.99, 614 (1977).
A. G . Brook, P . J . Dillon, Can. J. Chem. 47, 4347 (1969).
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Rertz, Adv. Organomet. Chem. 16, 33 (1977).
M . 7: Reetz, M . Kliment, M . Plachky, Chem. Ber. 109, 2716 (1976).
M . 7: Reerz, M . Kliment, M . Plachky, Chem. Ber. 109, 2728 (1976).
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11, 989 (1976).
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H . Schwarz, M . 7: Reetz, Angew. Chem. 88, 726 (1976); Angew. Chem.
Int. Ed. Engl. 15, 705 (1976); H . Schwarz, C. Wesdemiotis, M. 7: Reetz,
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[Sl] M . 7: Rretz, M . Kliment, unpublished results 1979.
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Liquid Column Chromatography with Chemical Derivatizations after
New analytical
By Georg S c h w e d t [ * ]
Modern liquid column chromatography (high-pressure liquid chromatography, HPLC) has
evolved in the last few years into a highly efficient and versatile separation technique. The
selectivity of an analytical process that depends upon a previous separation step can in
many cases be increased considerably by chemical derivatizations after the separation. In
addition, lower detection limits can be achieved in this way than in detection without derivatization. The physicochemical principles of these combined processes involving chromatographic
separation and chemical derivatization prior to detection (coupling of HPLC and a reaction
detector) are presented and discussed. The state of development is outlined, with a survey
of the more important applications so far described in the literature.
1. Introduction
The essential problems of modern analytical chemistry are
to increase the sensitivity and selectivity and to improve the
detection limits of analytical processes used to detect and
determine trace elements and low contents of organic substances in complex mixtures. During the last two decades
progress in this direction has been made possible mainly
with the help of physics and physical methods of measurement,
namely by novel analytical applications of physical effects
and by improvements in the available apparatus.
While the development of analytical chemistry up to about
1960 was mainly characterized by the analytical application
of chemical reactions and the discovery of new reagents for
[*] Prof. Dr. G. Schwedt
Analytische Chemie, Fachbereich 8 der Gesamthochschule
Adolf-Reichwein-Strasse 2, D-5900 Siegen 21 (Germany)
the classical gravimetric, volumetric, colorimetric, and photometric methods, it seems that the most significant part in
further development is nowadays played by physical methods
of measurement, for example spectroscopic methods.
In chromatography too, improvements in the equipment,
above all in the fields of gas and liquid chromatography,
have been responsible for a decisive improvement in separation
performances and hence in selectivity. Technological advances
in the manufacture of column packings with particle diameters
below 10 pm, and improvements in pumping techniques that
enable a constant pulsation-free delivery of the mobile phase
against high pressures, have in the last ten years transformed
classical liquid chromatography into the incomparably more
efficient high-pressure liquid chromatography (HPLC). However, compared to the analytical side of HPLC, the detection
stage has, as yet, not reached the same high level of sophistication as far as sensitivity, detection limits, and selectivity are
concerned. Nevertheless, developments are appearing that
. A I I ~ + w . Chem. Int. Ed. Engl. 18, 180-186 ( 1 9 7 9 )
0 Verlag Chemie, GmbH, 0-6940 Weinheim, 1979
S 01.00/0
once more endow the chemical side, i.e. chemical reactions
and reagents, with greater significance.
2. Reaction Detectors
2.1. Principles and Designs of the Analytical System
UV and fluorescence detectors with flow-through cells are
at present the most usual, and from the point of view of
instrumentation the best-developed detectors used with
HPLC?’]. T o improve the sensitivity and in particular the
detection limits it is often recommended that the substances
to be determined should be modified chemically to give compounds with higher molar extinction coefficients for UV detection, or compounds that can be detected fluorimetrically down
to lower detection limits than can be attained by UV detection.
Such derivatization can be performed either before or after
the chromatographic separation[’].
Derivatization prior to a chromatographic analysis, with
the aim of achieving more selective separations, and in particular lower detection limits than is possible with the original
compounds, has been successfully applied in chromatography
for some time[’. ’1. For this purpose the chemical derivatizations should be as quantitative as possible, and should lead
to one definite product. In contrast, if the substances are
to be derivatized after the separation step, reactions that do
not proceed to completion may suffice, even if they yield
several products, provided only that the signals to be measured
are strong and reproducible. Moreover, in this case there
is no longer any need for the sample preparation required
with derivative formation before the separation, which is often
laborious, time-consuming, and associated with losses of
1 l i q u i d - Chromatograph1
2.2. Diffusion Effects in the Reactors
In all reactors the chromatographically separated substances
exhibit “band broadening” caused by diffusion effects, which
can be described quantitatively.
The band broadening of a signal recorded in the detector
in the form of a Gaussian distribution curve can be described
in terms of the standard deviation 0 or the variance 0’. The
variances of individual parts of the analytical system are additive (cf. Table 1):
+ a:, +
(c: column, v : connections, td,g: total detection system, i. e. the
reactor and flow-through detector).
2.2.1. Open Reaction Tube
In an open capillary tube connected to the outlet of the
HPLC column via a T-piece, the variance as a function of
the reaction time (according to [6,71)is given by:
d: t
96 D,
Thus, for a given diffusion coefficient D, the band broadening
CT is proportional to the tube diameter d, and to the square
root of the reaction time t. Differences in band broadening
between ideal and geometrically deformed tubes have been
investigated by Hal& and Wulkling[61.
2.2.2. Packed Reaction Tube
Packed reaction tubes correspond to packed separation
columns in chromatography, but they do not have any retaining action. The dependence of the variance upon the reaction
time is here:
a1 Open reaction tube
b l Packed reactiontube
ci Mixing coil reaction unit
b l Fluorimeter
c I Polarograph
Fig. 1. System for liquid chromatographic analyses with chemical reactions
after the separation step. The combination of a reactor and flow-through
detector is called a reaction detector.
The analytical systems for liquid chromatography with
chemical reactions after the separation consist of a liquid chromatograph, a reactor, and a flow-through detector (Fig. 1, cf.
also L41).
The chemical reaction and the detection of the separated substances take place in on-line coupling after the chromatographic separation. In conformance with current practice,
in what follows we shall refer to the reactor and the flowthrough detector as the (chemical) reaction detector[’! The
reactor can consist of an open reaction tube (a capillary tube),
a packed reaction tube (a tube of greater diameter than a
capillary, packed with small particles such as glass beads),
or a mixing coil reaction unit such as those used in equipment
for automatic wet chemical analyses (AutoAnalyzersO). In
this reaction unit a peristaltic pump is used for pumping the
solutions through manifold tubes into the mixing coils. The
liquid stream is divided into segments with air bubbles (see
Fig. 2).
Aiigeu. Clierii. 1111. Ed. Engl. 18, 180-186 ( 1 9 7 9 )
(The equation used in [‘I has been rearranged.) The abbreviations are explained in Table 1. In this type of reactor the
band broadening can be reduced by using finer particles,
a higher flow-through rate, and a smaller tube diameter.
2.2.3. Mixing Coil Reaction Unit
In units of this kind the liquid stream is segmented by
air bubbles (Fig. 2) and the band broadening resulting from
diffusion effects in the longitudinal direction is thus reduced
to a minimum[’~9~’01.
The following equation, due to Snyder[’], gives the variance
as a function of the reaction time:
The optimal segmentation frequency n can in each case
be determined as a function of the diameter of the mixing
coil. The influences exerted by the flow rate F,, viscosity
q of the reaction mixture, and surface tension y have been
investigated thoroughly by
(For the abbreviations
in eq. (4), see Table 1.)
According to Hudina['z],the following relation exists for
the value of 40:
4 u = 2 y t 1 t df,(Pd,)
Table 1. Explanation of the abbreviations used and some definitions.
Concentration of a substance at the band maximum [ g . ~ m - ~ ]
Concentration of a substance in the sample solution [g-cm-3]
Mean liquid-film thickness on the walls [cm]
Internal diameter of connectors or tubes
Particle diameter [cm]
Tube diameter [cm]
Molar diffusion coefficient [cm'.sC']
Molar diffusion coefficient in water at 298 K [cm'. s '1
Flow rate down the column, space velocity [cm3.s- '1
Flow rate of the reagent [ a n 3 . s - '1
Height of a theoretical separation plate [mm]
Capacity-, mass distribution ratio
Length of a liquid segment [cm]
Column length [cm]
Mass l g l
Segmentation frequency [s '1
Number of theoretical separation plates
Pressure [bar]
Free cross section of a separation column
Radius of mixing coil
Resolution of two bands
Maximum resolution
Reaction time [s]
Over-all retention time [s]
Linear flow velocity [cm. S C ' ]
Sample volume [cm']
Ratio of liquid length/sum of liquid and gas lengths.[*,]
Surface tension [']
Porosity: fraction of the free cross section available 'to the eluent
Geometric constants for the packed reaction tube
Viscosity [ d y n e . s . ~ m - ~ ]
Band broadening [s] or [cm']
Band broadening in the column [s]
Band broadening in the reactor [s]
Band broadening in the whole detection system [s]
Band broadening in the connectors [s]
Here 0 represents the ratio of the liquid length to the
sum of the liquid and gas lengths (see Table I).
Fig. 2. Schematic representation of the segmentation of the liquid stream
in a mixing spiral reaction unit. r : radius of the glass tube (of the mixing
coil); d f : mean liquid-film thickness on the walls; I , : length of a liquid segment.
Sensitivity of a method: slope of calibration curve
Detection limit of a process: concentration for the measured quantity from
blank value plus three times its standard deviation
[*] By "liquid length" and "gas length" are meant the lengths of the liquid
and the gas segments, respectively.
Deelder and Hendricks" '1 give the following relationship
for the dependence of the variance on the mean thickness
of the liquid film df on the walls and on the length 1, of
a liquid segment (Fig. 2):
Eq. (4)[5]makes it possible to calculate the band broadening
from directly measurable or known magnitudes of the reactor,
while the application of the simpler relationships (5) and (6)
requires knowledge of ,the mean thickness of liquid-film on
the walls.
Further investigations concerning the dynamics of the analysis with continuously segmented flow have been performed
e.g. by Begg[l3], Thiers et a/."41,and Walker et ~ l . [ " ~ ,and
on band broadening in columns by Hnlirsz el ~ 1 . [ ' ~and
1 by
Huber and Hulsman["I.
.2.3 Comparison of the .Reactors and General Relationships
If we compare the variances or the band broadening for
several types of reactors in relation to the reaction time (Table
2), the mixing coil unit proves to be best. In practice, however,
additional broadening occurs as a result of diffusion in the
connections of the mixing coil to the chromatographic column,
in the air separator, and in the connection to the detector
(see, for example, ["I). Experimental values of o for several
reactors are shown in Table 3.
An open reaction tube is also suitable for very rapid reactions
lasting a few seconds. Indeed, when mixing coil reaction units
are used, greater band broadening than the calculated value
is observed due to the connectors; nevertheless, this type
of reactor is preferred to the two others for long reaction
times, particularly when several reaction steps are involved.
Table 2 Parameters for the calculation of band broadening u, in several reactor types
Dx25 3 5 ~ 1 0 . ~
0 02s
0 004
0 004
I 6
2 x 10-5
0 025
Internal tube didmeter d, [cm]
Diffusion coefficient D , [cm2.s1']
Flow rate Fi [cm'. s - '3
Viscosity q [']
Surface.tension 7 [dyne. cm- '1
Packing particle diameter d, [cm]
Segmentation frequency n [s-'1
Constants hl
Calculated variance as a function of reaction time [s2]
rrf 1.30r
1.97 x 10
I f
Angew,. Chem. Int. E d . Engl. 18, 180-1,\, (1979)
Table 3. Examples of experimentally obtained hand broadenings u, and
ux in several types of reactor.
at the band maximum cmaxto its concentration in the sample
co (after ["I):
Opeu reaction rube (after [21])
Determination of thioridazine in blood. Chromatography: partition with
ternary phases; reaction: oxidation with potassium permanganate; detector:
System: Sample loop + flow-through cell
Sample loop + flow-through cell
Conditions' r = 5 [s],
g,= 3.6
F , = 2 [cm'
(calculated from
+ open reaction
[cm], L=150 [cm]
The product co V, corresponds to the quantity of the sample.
In the reactor the sample solution is further diluted by
the addition of reagents and the band broadening" I:
Puc krd w w t m tube (after [70])
Determination of isoenzymes. Chromatography: in a modified cellulose
exchanger; reaction: transformation with IactateINAD' ; detector: photometer or fluorimeter.
System: column packed with nonporous glass beads.
Conditions: L = 30 [cm], d , = 0.41 [cm]. p = 7 [bar], d,
[cm-'I, t = 7 5 [s]
=5 x
10- [cm], u = 0.4
With the assumption of a Gaussian distribution, we have
(see [''I):
u,=3.1 [s] (calculated from Fig. 3 in [70] with H=0.5 [mm]) [*]
M i x i q [.oil reaction unit (after [ I
Determination of cyclohexanone. Chromatography: partition with ternary
phases; reaction: transformation with 2,4-dinitrophenylhydrazine; detector:
6 d
System: Mixing coil I : L = 2 [m], d,=0.24 [cm]
Mixing coil 11: L = l [m], d,=0.24 [cm]
Conditions: r=180 [s], u=0.15 [cm.s-l],k'=0.3 Rm,,=3(without areactor),
R = 2 . 4 (with a reactor): ~ , ~ >[s]7 decreases the resolution R by less than
u , = 5.7
Tsl (calculated from
amounts to only one-third of the value when the same reaction
d d
is carried out in an open capillary tube 15.25m long and with an internal
diameter of 0.05 cm [70].
Only at high temperatures does the packed reaction tube
seem to offer advantages["], since no tubing or plastic connections such as in the mixing coil reaction unit are required.
In more recent publications, Frei et
"1 have compared
the various possibilities of post-column derivatization.
For the ratio of the resolution of two signals, recorded
in the flow-through detector, and the resolution R,,, attained
by the chromatographic system with ot=olc and o=O, we
have (according to ''I):
= [1
+ a:d/az]
If a decrease of 5 % in the resolution R,,, is allowed for,
then old=0.33 crtc- From this condition we obtain a minimum
retention time of
(Example: old=2 [s], N=10000, tR2=400 [s]) at a given
resolution R for a pair of substances in dependence on the
number of theoretical separation stages N .
The dilution effect in liquid chromatography can be
expressed as the ratio of the concentration of a substance
Angew. Chrm. Int. Ed. Engl. 18, 180-186 ( 1 9 7 9 )
3. Examples of Application
Most of the so far described liquid chromatographic analyses
involvinga reaction detector are related to the fields of organic
chemistry or biochemistry. The analysis of amino acids has
already been carried out successfully for about 20 years, using
a chromatographic separation (ion exchange) directly coupled
to a chemical reaction stage before the detection, in automatic
reaction systems (with mixing coil reaction units)[221.Apart
from the classical ninhydrin[". 231, phthalaldehyde[29-3 2 1 ,
f l u o r e s ~ a r n i n e [and
~ ~ p~ y~ r~i ~d ~o ~ a~ l [ ~have
~ l been used for
the photometric or fluorimetric determination of amino acids
(see Table 4).
Peptide separations have also been combined with a reaction
step using phthalaldehyde[34] or f l u ~ r e s c a m i n e [ ~In
~ ] .part,
these methods have been extended to the determination of
arnine~['~27,30,331. In the analysis of biogenic amines such
as catecholamines, special chemical reactions are carried out
in mixing coil reaction units after the chromatographic separation: a) transformation with ethylenediamine[4'4'.421 and b)
oxidation to fluorimetrically detectable trihydro~yindoles[~~
481. Owing to the selective reaction to trihydroxyindoles, with
the aid of reversed-phase HPLC it is even possible to determine
the catecholamines in urine directly without preliminary separation (I4'], see also [851).
Other oxidizing agents such as potassium permanganate'211,
Ce(rv) sulfate[49 541, chromic acid[56.57],and p e r i ~ d a t e [5 7~1~ '
find application in the fluorimetric and absorption-spectrometricdetermination ofvarious organic substances in combination with liquid chromatography (see Table 4). Oxidizing compounds such as hydroperoxides are transformed with sodium
iodide; the iodine released is determined photometrically in
the through-flow[81.Redox indicators such as tetrazolium blue
and neocuproine are suitable for the analysis of reducing
Carboxylic acids can be detected using acid-base indicators
after ion-exchange chromatographic separation[60- 621.
Further reagents are listed in Table 4. For chromatographically
separated and chemically modified substances one can also
use electrochemical detection methods, such as the detection
of citrals with ~emicarbazide[~~!
Special reagents and reaction systems have been described
for enzyme analysis''", "1. In environmental analysis, the enzymatic inhibition of cholinesterase is used as an indication
4. Outlook: Development Trends
Selective chemical reactions with a variable flow-through
detector in combination with high-performance separation
systems offer the possibility of direct and sensitive analyses
of individual substances in complex mixtures such as urine
or blood without sample preparation.
Table 4. Examples of (chemical) reaction detector applications.
Substance or group of substances
amino acids [18, 231, amines [24, 251, polyamines [26, 271, y-aminobutyric
acid [28]
amino acids [29-321, amines [30, 331. catecholamines 1331, peptides [34], 5-hydroxyindoleacetic acid 1351. N-methylcarbamate [36]
amino acids [29, 37, 381, peptides 1391
amino acids [40]
catecholamines [4, 41, 421
Eth ylenediamine
Oxidizing agents
a) Potassium hexacyanoferrate(ll1)
b) Potassium permanganate
c) Cerium(1v) sulfate
d ) Chromic acid
e) Periodate
Sodium iodide
Tetrazolium blue
Acid-base indicators
Sullanilic acidjhi-(1-naphthyl)ethylenediamine
7-Chloro-4-nitrobenzofuran (NBD-chloride)
Acids (hydrochloric, sulfuric, acetic)
4-(2-Pyridylazo) resorcinol ( F I R )
L u m in o I
Ce(IV) sulfate
Detection [a]
catecholamines [43 - 481
thioridazine and metabolites [21]
carbohydrates 152, 531, phenols [54], 5.6-diarenecarboxylic acids [49-51],
hydroxycarboxylic acids [56, 571
hydroxycarboxylic acids [56, 571
hydroperoxides [S]
sugar [58]
reducing sugars [59]
carboxylic acids 160-621
hydroxycarboxylic acids [56, 571, uronic acids [63]
carbohydrates [64]
nitrosamide [65]
proline, hydroxyproline [66]
cyclohexanone [ I 11
glycosides [20], carbohydrates [67], estrogens 1681
citral [69]
enzymes [70]
enzymes [70]
enzymes [70, 711
organophosphorus compounds, carbamates. insecticides 172. 731
monofluorophosphate [74]
metal ions [75, 761
metal ions [77 -791
zinc [RO]
polythionates [81]
F, A
F, A
F, A
F, A
F, A
A. F
[a] A: absorption measurements; F: fluorescence measurements; E : electrochemical detection
Examples of such applications of reaction detectors have
been described, among others, for carbohydrates in urine and
serum152', for free proline and hydroxyproline in serum1661,
In inorganic analysis too, reactions after ion-exchange chroand for free epinephrine and norepinephrine in urine[481(Fig.
matographic separations with molybdate, metal reagents, or
3). Further examples are the direct determinations of dopamine
even Ce(1v) sulfate find some a p p l i ~ a t i o n [ ' ~ - ~ ~ !
serotonin in brain homogenates by reversed-phase chroThe examples set out in Table 4 are not differentiated
separation and reaction with phthalaldehyde
in terms of classical or modern HPLC in columns. According
(Fig. 4) (see also [851).
to Enge/hardt[s2],the borderline between HPLC and classical
Such analytical processes, especially when they are used
liquid chromatography is defined by a packing particle diameter greater than 50 pm for the latter. Snyder and K i r k l ~ n d [ ~ ~ ~for the trace analysis of organic substances, are mainly effective
in reducing problems connected with separation from the
characterize modern column chromatography as high-speed
material and the stability of the substances or derivatives
or high-performance liquid chromatography with a high separprepared for the liquid chromatography. Moreover, they
ation power and short separation times ranging from a few
shorten the analysis time compared to a process comprising
minutes up to an hour. Further examples of reactions in
separation, derivatization of the test substance, and chromatosystems with continuous through-flow in combination with
graphic analysis. Another objective of such systems that comclassical column chromatography are given in a monograph
bine HPLC and (chemical) reaction detectors is the separation
by Foreman and S t o c k ~ e / l [ ~ ~ ~ .
for organophosphorus compounds, carbamates, and insectiCides[72,73~.
Angew. Chrm. lnt. E d . Eiiyl. 18, 180- 186 (I9791
and determination of as many materials as possible in a single
operation. Examples of this are provided mainly by the analysis
of amino acids, of carbohydrates, and of metallic ions, which
are derivatized by means of group reagents and thereby determined all together after a chromatographic separation (see
Table 4). The precondition for the applicability of this process
f, [ m i n l
Fig. 3. Direct determination of epinephrine (E) and norepinephrine (NE)
in 200pl of urine by a combination of reversed-phase chromatography
(column: LiChrosorb RP 18, mobile phase: 0.0SM phosphate buffer p H 3,
flow rate: 1.5 ml- m i 6 I, pressure: 60 bar) with a (chemical) reaction detector.
IS denotes internal standard.
Flow diagram: I : Oxidizing solution: 0.3 M formate bufTer pH 4/0.1 M boric
acid/O. I "/, potassium hexacyanoferrate(llI)/2.10 - 3 % copper acetate (tube:
di 0.76 mm); 2: Air (tube: d, 1.42 mm); 3: Reducing solution: 5 % mercaptoethanol in wateri20 % sodium sulfite in water/lO M caustic soda, proportions
by volume I : 1 : 1 (tube: d, 0.76mm); 4: 4M acetic acidl4 %, boric acid (tube.
d, 1.14mm); MT: Main tube di 1.85mm; P: Peristaltic pump, F: Fluorimeter
(excitation wavelength 405 nm, fluorescence-edge filter 450nm, sensitivity
0.03 p4,'full scale); MC: Mixing coil, D M C : Double mixing coil (d, 2.4 mm)
Urine sample: 14.5 ng epinephrinelml and 59 ng norepinephrine/ml (corresponding to 2.9 ng epinephrine and 11.8 ng norepinephrine in the column).
is a selective chromatographic system with a high separating
efficiency. Thanks to developments in modern liquid chromatography, the analysis time in the case of amino acids has
been reduced from over 12h[221to less than 1 h13'!
Moreover, with the systems described, the accuracy of analytical results can be checked, as can be seen from the following example:
For the analysis of biogenic amines in biological material,
interference-free analytical processes combining separation
and enrichment processes (ion exchange, liquid-liquid partition) with selective chemical reactions have been developed.
Considering the example of serotonin, HPLC and chemical
reaction with fluorimetric measurement after the separation
have shown that with urine samples the separation processes
with n-butanol usually used for brain specimens give
erroneous (high) values. In the chromatogram alongside the
Anyen Climni. Int. Ed Engl. 18. 180-186 ( 1 9 7 9 )
f , [ m i n l --+-
Fig. 4. Direct determination of dopamine (DA) and Serotonin (Ser) in 50 pl
of brain homogenate (1.5g of rat brain homogenized in l 0 m l of 0.1 N hydrochloric acid) by a combination of reversed-phase chromatography (column:
Li-Chrosorb RP 18, mobile phase: 20 % methanol in an aqueous solution
of 0.4M acetic acidiboric acid pH 3.2, flow rate I . 2 m l . m m ~ ' . pressure:
80 bar) with a (chemical) reaction detector.
Flow diagram: 1 : Reagent: phthalaldehyde, 0.02 wt-0!,/0.05 V O I - % ~ mercaptoethanol in O.2M borate buffer pH 9 (tube: d, 0.76mm); 2 : Air (tube: d,
0.76mm); MT: Main tube (d, 1.14nim); P: Peristaltic pump; F: Fluorimeter
(excitation wavelength 365 nm, fluorescence edge filter 450 nm, sensitivity:
0.3 gA/full scale): MC: mixing coil.
serotonin signal a further signal was recorded, which is measured as serotonin when no separation has been performed,
in spite of the selective reaction (with phthalaldehyde in
hydrochloric acid at 80°C)[861.
Received: May 23, 197X [A 261 IE]
German version: Angew. Chem. 91, I92 ( I 979)
Translated by AD-EX (Translations) Ltd., London.
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Structural Chemistry of Fluorides and Oxide Fluorides of Nonmetals
By Konrad
The structural features of the nonmetal fluorides and oxide fluorides can now be explained
and useful predictions can be made. The same applies in part to the chemistry of this class
of compounds. Statements concerning structures can easily be made on the basis of the electron
pair repulsion model (VSEPR theory). Some rules for the number of ligands provide structural
predictions for larger units than isolated molecules or ions. This is important for the fluorides
and oxide fluorides of the heavier elements. This class of compounds has its limits in the
lighter noble gases which, even with fluorine, form only weak bonds or no bonds at all.
1. Introduction
The number of research papers on the fluorides and oxide
fluorides of the nonmetals runs into thousands. A complete
[*] Priv.-Doz. Dr. K. Seppelt
Anorganisch-Chemisches Institut der Universitat
Im Neuenheimer Feld 270, D-6900 Heidelherg 1 (Germany)
survey of the literature cannot be given in this article-for
this the reader may be referred, for example, to specialist
review periodicals[' - 31. Here we shall be considering common
features in the structural chemistry of this class of compounds.
Simple rules are now known which help us to predict the
structures of compounds. If we confine the discussion to the
nonmetals, and permit only oxygen and fluorine as ligands,
we are in a position to make almost complete structural
Angew. Chrm. In[. Ed. Eiigl. 18. 186-202 ( 1 9 7 9 )
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