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Molecular Complexes and Oxygen Adducts of Tetrapyrrole Pigments.

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Molecular Complexes and Oxygen Adducts of Tetrapyrrole Pigments
By Jiirgen-Hinrich Fuhrhop[*]
Metalloporphyrins not carrying functional groups and the n-radicals of these species form
comparably stable coplanar n-n-dimers by means of various types of weak interactions. Chlorophyll a and other derivatives containing carbonyl groups add water and aggregate into molecular
complexes by means of hydrogen bonds. Such aggregates are of special interest in connection
with a new hypothesis for the photo-oxidation of water to oxygen during photosynthesis.
Finally, some new discoveries concerning the structure and reactivity of heme-oxygen complexes
are discussed.
“ I think that a great field which we can call chemistry or
can call molecular biology, ifwe want, in which there are possibilities of tremendous progress, is thefield of the explanation of
the highly specific weak interactions between molecules showing
up in biological systems.
I think that the various phenomena of biological specficity
are determined by the rather weak interactions between molecules
... the sitting together of two molecules over a considerable
area so that the forces of attraction are summed up over this
area into an effective bond between the molecules. Here we
are pretty largely ignorant still. We don’t know why it is for
the most part ..., why one drug is physiologically active and
another substance is not physiologically active. We may have
some rather vague general ideas about why this takes place,
but these need t o be made specific. We need to get a penetrating
and reliable theory of the weak interactions between molecules
responsiblefor biological specificity and in general of the dependence of the physiological properties of substances on their
molecular structure.
I consider this a branch of chemistry and I think that this
is afield in which there should be tremendous progress during
the next decade or two”.
Extract from an interview with ProJ Linus Pauling ( M e n
and Molecules, the unique ACS radio series No. 366, “The
Committed Scientist”, around 1970).
1. Introduction
Linus Pauling’s answer to the question on further development of chemistry opens up the chapter of modern natural
product chemistry of greatest interest to the author of this
review. Not only the determination and synthesis of primary
structures appear to him to deserve the closest attention,
but also the discovery of the specific interactions between
biologically active materials. For the organic chemist this
means, first of all, the preparation and analysis of simple
molecule complexes and an attempt to understand the fundamental noncovalent bonding forces. For such work associations of symmetrical molecules are initially preferable, since
their spectra, crystal structure, and reaction patterns are naturally easier to interpret than those of structurally very complex
components. Among the associations the simplest to analyze
are generally the dimers, since their properties can be corre[*] Prof. Dr. J.-H. Fuhrhop
Gesellschaft fur Biotechnologische Forschung mbH
Mascheroder Weg I , D-3300 Braunschweig-Stockheim (Germany)
and lnstitut fur Organische Chemie A der Technischen Universitlt
Schleinitzstrasse, D-3300 Braunschweig (Germany)
lated directly with one monomeric molecule. Dimers of a
natural product, often with solvent molecules as integrating
components, are therefore usually the first object of study.
Once the noncovalent reactivity of a class of compounds
has been more or less clarified, complexes with other types
of natural products can be analyzed, and here the choice
of mixed associations will be greatly influenced by biochemical
findings. The present review describes the properties of some
important molecular complexes of porphyrins, chlorophylls,
and bile pigments, as well as those of their derivatives. At
the same time, when it appears useful, the relationships to
observations and models used by the biochemist and biophysicist will be indicated.
2. Dimers and Higher Aggregates of Porphyrins not
Possessing Functional Side Chains
Porphyrins and their metal complexes behave in solution
similarly to the polycyclic arenes: they form sandwich dimers
with an interplanar separation of 3.5-4A (Fig. 1 a). The
bonding relationships in such dimers have been briefly discussed for the ground state by Chandra and Sudhindra for
the cases of naphthalene and anthraceneI’]. The following
were considered to be the important components of the bonding forces in dimers:
a) Electrostatic interactions between the o-electron charges
on the ring carbons (ca. -0.1) and the positive partial charges
on the hydrogens (ca. +0.1) of the neighboring molecule;
b) Delocalization ofthe K-electrons over both molecules :
c) x-x-Dispersion forces, i. e. forces of attraction between
the n-electrons of one molecule and the atomic nuclei of
the other. Coulson has shown that, in comparison with these,
in molecules containing more than four double bonds the
o-o-dispersion forces are negligibly small[*] (van der WaalsLondon forces).
The bonding interactions are opposed by two types of repulsion forces : those between x-electrons and those between positivized hydrogen atoms or substituents in neighboring molecules. The bonding enthalpies of naphthalene and anthracene
dimers amount to about 3 kcal/mol; for porphyrin dimers
appreciably larger values have been measured (6 to 10 kcal/
mol)L3], presumably due simply to the larger molecular surfaces, which lead to larger van der Waals-London forces.
d) Hydrophobic or, more generally, “solvophobic” effects play
an important part, presumably because of the large surface
of the porphyrins. Effects of this kind in aqueous media have
often been in~estigated[~!
If apolar molecules are suspended
Angew. Chem. I n t . Ed. Engl.
1 Vol. 15
( 1 976) No. 1 I
in an aqueous medium, the hydrogen bonds of the water are
broken without their place being taken by other polar interactions. To reduce to a minimum this energetically unfavorable
boring of holes through the water structure, the hydrophobic
agents are compressed to molecular aggregates, to oil droplets.
It may be assumed that the aggregation of porphyrins is
favored by analogous disturbances in the solvent structure
of polar organic solvents151such as methanol and acetonitrile.
e) n-Rudiculs of the chromophore can bunch together to
diamagnetic dimers, whereby there is formed either a new
o-bond in the molecular plane (e.g.the dimer of the triphenylmethyl radical, AH = - 11.5 kcal/rnol)['. or a n-x-bond perpendicular to the molecular plane (e.g. the dimer of the N-ethyldihydrophenazinyl radical, AH 2 - 2 kcal/mol)'8'.
None of the above five types of bonding forces can be
measured directly. Our knowledge is limited to the total bonding enthalpies and structures of the dimers, from the changes
in which on variation of chromophore, substituents, and the
medium one can draw qualitative conclusions about the nature
of the bonding forces.
(la), R
(lh), R
(lc), R
(Id), R
(le), R
(If), R
(lh), R
(li), R
= H, M = 2
CH,, M = 2 H
CzH5, M = 2 H
H, M = Mg
H , M = Zn
C2H5, M = M g
larly, all the hydrophobic derivatives of the natural porphyrins
and chlorophylls, e. g. protoporphyrin dimethyl ester (2 a )
( h i , R = C H = C H ~ ,M = 2 H
12h), R = CzH5, M C O "
(2c), R = CH-CH2, M = Felt
(3a), RI =
(361, R1 =
M =
( 3 r ) , R1 =
(3d), R1 =
R~ = CH,, M = 2 H
CH3, E2 = Phytyl,
R 2 = CH,, Ivl = Mg
R 2 = C2H5, M = Mg
and methylpheophorbide a (3 a ) , are very readily soluble
in many organic solvents[g1.These surprising and by no means
trivial solubility differences are probably caused by space
filling by the alkyl side chains, which prevent aggregation
beyond the dimer stage (Fig. 1). The crystal structures of
nearly all porphyrins studied so far-here, however, including
porphine[". "]--contain porphyrin dimers as repeat units
(separation of porphyrin planes 3.4 to 4.2 A).
C2H5, M = Z n
CzH5, M = C U
C2H,, M = V O
Porphine ( I a), the unsubstituted parent compound of the
porphyrins, is sparingly soluble in organic solvents and exists
in the form of ill-defined aggregates. This is expressed, for
example, in complicated, strongly solvent-dependent, and often
time-dependent electronic spectra with broad shoulders on
the absorption bands. Octamethylporphyrin (1 b ) is still more
strongly aggregated and almost insoluble in all solvents, presumably because of its greater molecular weight, the higher
electron density in the chromophore, and the greater number
of hydrogen atoms. Octaethylporphyrin (I c), however, and
all higher homologs are more soluble by one to two orders
of magnitude than porphine in chloroform, pyridine, etc. Simi-
Fig. 1 . a) Unsubstituted planar compounds showing large flat areas, which
include e . g . , unsubstituted porphine ( 1 a), and form dimers or higher aggregates in which the molecular planes lie one over the other with a separation
of 3.5 to 4 S A . b) Porphyrins with several fairly large substituents, e.y.
ethyl groups, still form dimers but further aggregation is difficult. Radicals
from porphyrins and chlorophyll, for example, afford diamagnetic dimers
in completely reversible reactions but d o not form insoluble polymers. c)
The tendency t o form dimers and space-filling by the substituents account
for the commonest crystal structure (here shown only two-dimensionally)
of porphyrins and their metal complexes.
100 G
Fig. 2. When the dimer of a porphyrin radical contains copper(i1) ions, e.g. ( 1h ) , a molecule in the triplet state results, since the two
unpaired copper electrons are localized largely in the porphyrin plane and cannot pair.
Anyew. Chrm. I n [ . E d . Engl. j Vol. I5 (1976) N o . 1 1
Electrochemical oxidation of the magnesium (1 d ) or zinc
(1 e ) complex of porphine to the rr-radical cation leads to
formation on the platinum electrode of a black precipitate
which is insoluble in all solvents including concentrated sulfuric acid; it is presumably a graphite-like polymer of porphine" 'I. x-Radical cations of the metal complexes of octaethylporphyrin (1 f) to ( I h ) , however, do not polymerize but
instead form only stable x-x'-dimers in many solvents, e.g.
acetonitrile or methanol/chloroform (10: 1). The bonding
enthalpy has been measured as 14 to 18 kcal/mol, which is
extremely high when compared with those of other radical
dimers (see above). Moreover, a new absorption band is
observed in the near infrared, with an oscillator strength of
about 0.7['31.Although no X-ray structure analysis of these
diamagnetic radical dimers has yet been successful, their structure can be derived from the ESR spectra of the copper(1r)
complexes, e . g . ( 1 h ) . The unpaired electron of the copper([[)
ion, which has the d9 configuration, is localized to the extent
of 98 % in the dX2--yZorbital in the porphyrin plane. The
ESR spectrum of the rr-x'-dimer of the rr-radical cation shows,
as in Fig. 2, hyperfine splitting by both copper ions, and
the copper-copper separation can be estimated as 4.2k from
the coupling constants D of the signal (Fig. 2)[14].The separation of the two copper ions, which corresponds approximately
to the extension of the d-orbitals, is intelligible only if the
two porphyrin planes are parallel to each other.
In the meantime we detected x-n'-dimers of porphyrin radicals from porphyrins" 31, c l i l o r i n ~ ' ' ~and
~ , oxophlorins" 'I,
copper[l41, vanadium[141,and nickel complexes,
and in such different solvents as methanol['31 and toluene['4!
Bond enthalpies of 14 to 18 kcal/mol were found in all cases.
From these results it can be concluded that both delocalization
of n-electrons (bonding force b) and the simultaneous formation of a x d - b o n d perpendicular to the porphyrin plane
by pairing of the lone electrons (bonding force e) are the
determining bonding forces in these dimers. Furthermore,
the bond enthalpies in polar solvents (methanol, water, acetonitrile) appear to be about 2 to 3kcal/mol greater than in
apolar solvents['31(bonding force d).
A splendid exotic will form the last example of porphyrin
dimers not containing functional groups. If a porphyrin is
treated in tetrahydrofuran/dichloromethane with mercury(l1)
acetate, one obtains a complex containing three mercury,
two acetate, and two porphyrin ions (Fig. 3), whose NMR
spectrum shows weak splittings due to the interaction of the
two porphyrin nuclei['6!
On addition of pyridine the dimer breaks apart and the
normal mercury complex is formed. This unusual association
presumably owes its existence to two unusual properties of
the mercury(1r) ion: its relatively large ionic radius of 1.1 A,
which prevents its entry into the interior of the porphyrin,
and its tendency to form covalent bonds, which makes loss
of acetic acid difficult.
So far only the dimers of the simplest porphyrins and
their metal complexes have been described above. All these
are well defined and their bonding can be qualitatively well
explained. However, we have already learnt about seven types
of bonding, and it should be clear that bio-(in)organic chemists
who plan syntheses of new molecular complexes will be faced
with manifold problerns[''~. The next stage of complexity
is reached with porphyrin derivatives that contain carbonyl
3. Dimers and Higher Aggregations of Porphyrin Derivatives Containing Carbonyl Groups
Aldehyde or ketone groups conjugated with pyrrole or porphyrin rings act as strong electron donors['*] and form hydrogen bridges with O H and N H proton donors. The strength
of the bond is the greater the more easily can the O H or
N H bond be broken and the richer is the carbonyl group
in electrons. In other molecules NH-0 and OH-0 bond
lengths of ca. 2.7 to 3.0A and bond angles between 120
and 180" have been found["". Electrostatic interactions have
most commonly been assumed as the bonding principle, i. e.
the positive hydrogen atom is attracted by two heteroatoms
and simultaneously decreases the repulsion between them.
In accord with this, Allen'2o*2 1 1 recently formulated a simple
and convincing model of the hydrogen bridge in which the
bond energy ED of a series of hydrogen-bridged dimers is
given by eq. (a):
where K is a constant, pA-,, is the dipole moment of the
monomer providing the proton, A1 is an expression containing
the difference between the ionization potentials of the two
atoms bound by the proton, and R is the separation between
these atoms.
Fig. 3. Mercury(l1)ions and porphyrins form together double-decker sandxi i,.h
complexes that readily rearrange to normal porphyrin complexes. The structure or this dimer was derived from N M R spectra and elemental analyses.
Octaethyl-5,10,15,20-tetraoxoporphyrinogen(octaethylxanthoporphyrinogen) ( 4 ) forms the simplest known hydrogenbonded aggregate of a porphyrin on which the important
structure-controlling factors of this weak interaction can be
demonstrated[23,241. The molecule contains four acidic N H
protons, which bind two water molecules, one above and
one below the center of the p o r p h y r i n ~ g e n ~The
~ ' ~ . requirements that the hydrogen bonds should be as nearly linear
as possible, and that the van der Waals radii of the atoms
concerned permit the porphyrinogens and the oxygen atoms
A i ~ g n v .Chmi. Inr. Ed. Enyl.
:I KA. 15 ( 1 9 7 6 ) N o . I f
zinc-bound methanol of the second porphinoquinone is
attached to the first molecule in a similar manner, so that
a dimer is formed in which the parallel porphyrin planes
are shifted with respect to each other by half the length of
the molecule (Fig. 5).
L H ,
Zn N
Fig. 5. Two 5,15-dioxoporphodimethene(“porphinoquinone”)molecules are
linked by methanol molecules bonded on the one hand coordinately to
the central zinc ion and on the other by hydrogen bridges to a carbonyl
group of a neighboring molecule. Semiquinone radicals formed on reduction
are probably stabilized by this dimer formation.
Fig. 4. Water i s bonded by linear NH-0 bridges above and below the
center ofthe xanthoporphyrinogen (4), leading to a wavy molecular structure.
The protons of the water molecule form hydrogen bridges with the carbonyl
groups of neighboring porphyrinogen molecules. The crystal lattice resembles
long tubes stacked on one another, within which water molecules are fixed.
The structure exemplifies an economical principle that is repeatedly observed
in the molecular complexes discussed here, namely that all the acidic protons
and all the oxygens are, whenever possible, linked by hydrogen bridges.
of the water to approach each other to no closer than about
2.7 A, result in rotation of the pyrrole rings out of the porphyrin
plane (Fig. 4). The dihydrate also contains the four acidic
protons of the water molecules; these bind four carbonyl
oxygen atoms of neighboring porphyrinogen molecules in
a symmetrical manner, and this leads to cylindrical linking
of the chromophore chains. The whole structure thus resembles
a stack of interconnected tubes in which the positions of
the water molecules are fixed with well-defined separations
of 2.4 and 4.8p\. The effect that the water has on the crystal
formation of (4) can also be easily demonstrated macroscopically: the water of crystallization can be removed only above
150°C under high vacuum, and the crystals then disintegrate
into a powder.
Reduction of xanthoporphyrinogens by sodium tetrahydridoborate leads to the formation of 5,15-porphinoquinones
such as ( 5 a ) , which have recently become a center of interest[15,22,26-281. 0n chromatography of the zinc derivative
(5 b ) on silica gel a stable dimer can be isolated, whose peculiar
chemical reactivity (see Section 6) can be understood only
when the crystal structure is recognized: each central zinc
ion is bound to a molecule of methanol whose proton is
hydrogen-bonded to the neighboring carbonyl oxygen ; the
Anyew. Chmi. I n : . Ed. Eiiyl.
Yo/ 15 ( 1 9 7 6 ) No. I I
Similar but much more complicated relationships are found
in the case of chlorophyll (3b). Here the central magnesium
ion binds one water molecule, which can be attached to the
carbonyl group of the carbocyclic ring E. Moreover, the
magnesium ion itself is probably sufficiently electrophilic to
add to the b-0x0 ester group of ring E of a second chlorophyll
molecule. These basic possibilities of association lead to a
large number of dimeric and polymeric aggregates which have
been clarified by very thorough NMR and IR investigations,
mainly by J . J . Katz et a!. In the present review only the
two most important dimer structures elucidated by Katz and
an X-ray structure analysis by Strouse will be discussed; details
of the methods used in these investigations will be found
in reviews by K a t ~ [ ” - ~and
~ ] in some other paper^[^^-^^].
The principles of spectroscopic analysis of chlorophyll
aggregates are based mainly on the following facts :
1. The IR absorption of the 0x0 group in the carboxylic
ring E lies at 1695cm- I . If chlorophyll aggregates in extremely
dry apolar solvents (e.g. CCld), the intensity of this band
diminishes and an “association band” appears at 1652 cm- I .
The origin of this band can be seen in the formation of
a C=O-Mg
group, as indicated in Fig. 6.
Fig. 6 . In the anhydrous dimer of chlorophyll the central magnesium ion
ofone moleculeis bound coordinately to thecarbonyl groups ofthe carbocyclic
ring E of the other molecule. The structure is based on IR and N M R
2. In a dimer according to Fig. 6 some parts of the two
chromophores lie very close to one another, while others
are further apart. Since strong ring currents are induced in
macrocycles of the porphyrin type in the NMR experiment,
conclusions can be drawn about the structure of the aggregates
from changes in the chemical shifts, e . g . of proton signals
of the substituents, on increasing the concentration: the larger
the shift, the closer are the two macrocycles in the region
concerned. Addition of a disintegrating solvent at relatively
high concentration is often used as a test: the chemical shifts
must then return to values corresponding to the monomer.
Analogous I3C-NMRmeasurements lead to similar results[35!
3. In hydrated chlorophyll aggregates the band at 1652 cm-'
is replaced by absorption at 1638cm-', which is assigned
to a C=O ...HO(H)-Mg grouping: a water molecule is
inserted between the magnesium ion and the carbocyclic ring
E of the neighboring molecule, and a dimer having the structure
shown in Fig. 7 is obtained. This too is supported by extensive
NMR data.
given in Fig. 8. One water molecule occupies the fifth coordination position of the magnesium. A second water molecule
is joined to the first and to the carbonyl oxygen of the ester
group on ring E by means of two hydrogen bridges. In this
Fig. 8. X-ray molecular structure of ethylchlorophyllide a ( 3 d ) .Two molecules
of water link the magnesium ion intramolecularly to its own carbocyclic
ring E and intermolecularly to two further molecules. The resulting network
structure probably corresponds in general to the structure of the light-gathering chlorophyll aggregate in oiiw. o = >CO; 0 = H 2 0 ; m = Mg.
Fig. 7. If a water molecule is added to the anhydrous chlorophyll dimer
(Fig. 6) a new dimer is formed, containing defined hydrogen bonds. The
structure follows from IR and NMR data.
Under many different conditions the dimers can be converted into higher aggregates, whereupon shifts of the 660nm
chlorophyll absorption to 740 nm are observed in the electronic
spectra. The structures of the aggregates are in many cases
proved by use of deuterated derivatives, other metal complexes,
or metal-free bases, by molecular-weight determinations, elemental analyses, etc. However, we think that complete certainty about such complex structures as those in Figs. 6 and
7 cannot be provided by NMR, ESR, or IR experiments,
no matter how careful they are. Only X-ray structure analysis
provides a trustworthy guide to such formations. If, on the
other hand, the structure of fhe molecular aggregates in the
crystal is in accord with all spectroscopic structural parameters
obtained for a solution, then it appears permissible at the
present time to conclude that the environmental relationships
of at least two molecules are identical in solution and in
the crystal.
Some years ago, in fact, Strouse succeeded in clarifying
the structure of a dihydrate of ethylchlorophyllide a ( 3 d )
by X-ray analysis[36?The important structural features are
way one proton of each water molecule remains free for intermolecular bridging. The proton of the water bound to magnesium binds the ketone oxygen atom of ring E of a neighboring
molecule, in complete agreement with Katz's dimer shown
in Fig. 7. A chlorophyll chain is thus formed (shown horizontal
in Fig. 8). The intramolecular unbound proton of the second
water molecule is linked to the carbonyl oxygen of the ester
group on ring E of another molecule, whereby a second chlorophyll chain arises (that show vertical in Fig. 8). This structure
provides no contradiction of importance to the structures
proposed by Katz, but supplements them in important points
about which the spectroscopic data convey no information.
The reason for this is clear: superposed porphyrin macrocycles
can be recognized at once in the NMR spectra, but porphyrin
molecules lying side by side can barely be distinguished from
Before leaving the field of tetrapyrrole chromophores held
together by hydrogen bonds, we can compare the simple
crystal structure of xanthoporphyrinogen dihydrate [ ( 4 ) ] (Fig.
4)with the complicated structure of chlorophyllide a dihydrate
[ ( 3 d ) .2H20] (Fig. 8). In the former the two water molecules,
one above and one below the plane of the chromophore,
together with the bridge bonds stabilize a structure corresponding to bundles of tubes within which water molecules
are fixed. In the magnesium complex ( 3 d ) the two water
molecules lie on the same side of the chlorophyll derivative
and by analogous interactions form a network on whose
surface the water is coordinated. In both cases the structures
can be derived directly from the properties of the components
[essentially the acidity of the NH protons in ( 4 ) , the favored
fivefold coordination of the magnesium in ( 3 d ) , and the electronegative carbonyl groups in ( 4 ) and ( 3 d ) ] . The fundamental principles are clearly a) neutralization of positive (on the
central metal) and negative (on the carbonyl groups) partial
charges by attachment of water and b) coordinative saturation
of all the protons capable of hydrogen bonding.
Angew. Chem. I n t . Ed. Engl.
1 Vol. 1 5 ( 1 9 7 6 ) No. 1 1
4. An Open-Chain Dimer
Photo-oxidation of metalloporphyrins with molecular
oxygen leads to f~rmylbiliverdins[~’* e. g . the zinc complex
(6), i.e. it leads to fission of the macrocycle at a methine
bridge. In this way conformational changes become possible
that appear to be excluded for the rigid porphyrin ligands.
If (6) is crystallized from neutral solvents, brown plates are
obtained (h,,,,, = 830 nm) whose X-ray structure analysis displays a cyclic-planar ligand (Fig. 9)13’]. The same conformation
in solution was proved by ESR spectroscopy for the copper
complex of that ligand[401.
Fig. 10. If a solution or biliverdinate ( 6 ) i s acidified, the water molecule
is split off. The now fourfold-coordinated zinc ion strives toward a tetrahedral
environment and attains this by reversible formation of the his-helical dimer
drawn schematically (see Ref. 1391).
of the surrounding nitrogen electrons in this way. It is now
striking to find that the reaction is easily reversible: if an
acid solution of the bis-helical dimer is neutralized, the structure shown in Fig. 9 is regenerated.
5. Dissociation of Aggregated Porphyrins
Hemes and chlorophylls aggregate both in aqueous solution
and in an apolar medium. If the porphyrin units isolated
from natural systems are required, the chromophore is fixed
in a polymeric matrix. Stable iron(I1)-oxygen complexes, for
example,can be formed only if reaction with a further molecule
is prevented (see below). For chemical and physical investigations of monomeric metalloporphyrins the synthetic porphyrins ( 7 a ) to (7c) are particularly suitable, built into
micelles rather in the manner shown in Fig. 11. Proof of
the resolution of ( 7 a ) and ( 7 b ) into monomers in the micelles
was provided by ESR spectroscopy for the paramagnetic copper complexes (7d) and ( 7 e ) : if these copper complexes
were dissolved in water an unresolved ESR spectrum was
observed, whereas on addition of the micelle-forming lauryl
sulfate the hyperfine structure of the monomeric copper complexes appeared[41!
Fig. 9. Molecular structure of the zinc complex of synthetic octaethylformylbiliverdin (6). One water molecule is bonded coordinately and presumably
stabilizes the planar arrangement of the four nitrogens of the biliverdin
One structural peculiarity was striking, namely that the
central zinc ion in (6) binds a water molecule. If the solution
of (6) is acidified a reversible color change from brown to
green (A,,, = 730 nm) is observed. Structure analysis of the
green crystals disclosed a bis-helical dimer in which the two
zinc ions were each bonded to one-half of both chromophores
(Fig. 10). For this rearrangement the driving force is once
more easy to identify, and once more a new effect comes
into play: it is assumed that as the pH decreases the water
molecule of the hydrate shown in Fig. 9 is protonated and
immediately thereafter splits from the zinc ion.
Whereas the square-planar arrangement of ligands of the
biliverdin chromophore around the zinc ion is stable in the
case of the fivefold coordinated metal, after dehydration the
now fourfold coordinated zinc seeks to attain a tetrahedral
configuration of the four surrounding nitrogens. This is in
no way possible with one bilatriene chromophore. Instead,
two formylbiliverdin molecules intertwine so that each of
the two pyrromethene units of one chromophore can engage
two corners of a tetrahedron. In fact both zinc ions in the
structure shown in Fig. 10 attain a tetrahedral arrangement
Anyrw. Chum. Ini. Ed. Enyi. 1 & I / . I5 (1976) N o . 1J
(7a), M = 2 H, R = (CHz)s-COOH
(76), M = 2 H , R = (CHz)g-CH=CH-S03H
(7cJ, M = 2 H, R = ( C H ~ ) ~ - & C ~ H S ) ~ C H ~
(7d), M = C U , R = (CHz)g-COOH
( 7 e ) , M = C u , R = (CHz)a-CH=CH-SO,H
Hemoglobin contains four heme molecules, each of which
consists of one iron(I1)-porphyrin and is rigidly coordinated
to one imidazole base of the globin. The average separation
of the porphyrin ligands is about 3 0 i (Fig. 12)[42*43!Nevertheless, there is a very close relationship between all four chromophores; if the sixth coordination site of one heme is loaded
with oxygen, then all four subunits of the hemoglobin rearrange
so as to make easier similar loading of the other heme units.
This phenomenon was the starting point of the Jacob and
functions. The protein complex as a whole conducts excitation
energy from the “antenna” chlorophyll molecules, which
absorb sunlight, to the photochemical centers where the light
energy is converted into chemical energy. Stepwise energy
transport by the protein is obviously possible, although no
direct overlapping of the chlorophyll orbitals occurs and
although the space between the chlorophyll molecules consists
of purely hydrophobic regions of little structure. Experimentally, fluorescence and circular dichroism measurements, which
will not be discussed here, prove that all seven bacteriochlorophyll molecules of one subunit are connected with one another
by exciton interaction^[^'! For separations >20& such as
must be overcome for energy transport between the subunits,
the Forster mechanism can be brought into play[45].
Fig. 11. By a suitable choice of detergents and substituted porphyrins, monomolecular porphyrin solutions are obtained in which the chromophore is
localized in the hydrophobic interior of the micelles.
Monod allosteric model of enzyme regulation and is still today
a central theme in structural chemistry.
It is now known from X-ray structure analyses of deoxyhemoglobin and of (partially decomposed) oxyhemoglobin that
in the total course of oxygenation the essentially hydrophobic
contact positions of the subunits change along the full lines
in Fig. 12, although the overall structure of the protein remains
largely unchanged. It must now be assumed that the first
oxygenation leads to extensive disturbances of the interactions
between the subunits, and that this accelerates the oxygenation
of the other
Fig. 12. The fixed relative positions of the heme molecules in oxyhemoglobin
prevent their direct interaction, so that autoxidation of the heme is prevented.
Nevertheless, adsorption of oxygen occurs through the four heme molecules
by a cooperative action which is achieved by drastic changes in conformation
on addition of the oxygen (the allosteric effect). The full lines indicate mainly
hydrophobic interactions between unlike chains, while the broken line indicates the mainly polar interaction between like chains.
The structure of the unusual, water-soluble protein from
Chlorobium limicola with a molecular weight of about 130000
and a total of twenty-one bacteriochlorophyll molecules[451
was recently clarified by X-ray spectroscopy. First it was
shown that there were three identical subunits of molecular
weight 42000, each containing seven bacteriochlorophyll molecules, and their structure was elucidated (Fig. 13). Here too
it was assumed that the seven chromophores, each separated
from the next by 12 supported each other in their biological
Fig. 13. The here strongly scbematized molecular structure of a water-soluble
bacteriochlorophyll protein shows that the chromophore molecules are not
aggregated and that the space between them is strongly hydrophobic. Exciton
and Forster mechanisms are discussed in relation to the transfer of quanta
between the bacteriochlorophyll molecules of this light-conducting complex.
In nature all intermediate stages are found between, on
the one hand, very extended aggregates resembling a crystal
surface, in which the porphyrins are directly coupled to one
another and, on the other, complexes in which high-molecular
proteins contain isolated porphyrin islands. These complicated
structures have often been characterized only by electronic
spectra and lengthy biochemical interpretations. The few complexes discussed in this review form a solid nucleus for further
work; they show that porphyrins usually act cooperatively
and that the structure of biological, high-molecular porphyrin
complexes at once also defined the mode of action: the “crystal
flatness” of extended chlorophyll is suitable for collection
of light, the parallel arrangements of chlorophyll chromophores with a separation of 20A are optimally suitable for
the conduction of light, and the regulation of oxygen-absorption is best effected by flexible proteins with isolated porphyrin
6. The Chemical Reactivity of Porphyrin Aggregates
Since the aggregates described in the preceding sections
have been discovered and elucidated only recently, very little
is known of their chemical. reactivity in comparison with
the monomers. Fundamental differences are to be expected
above all in photo- and redox-chemistry, since in sandwich
Anyrw. Chem. I n t E d . Enyl.
f Vol. 1 5 ( 1 9 7 6 ) No. I 1
dimers the unpaired electrons of triplet states and radicals
can be smeared over the two n-systems and the axial ligands.
Two examples, recently discussed but still somewhat speculative, may illustrate this point.
If the zinc complex ( 5 6 ) is reduced by dithionite in hexamethylphosphorotriamide, then only the dimer with bridging
methanol forms a semiquinone radical that is stable for hours
under nitrogen, whereas the monomer decomposes irreversibly
under these conditions within a few seconds. Furthermore, the
ESR signal of the semiquinonoid radical is extremdy narrow
( < 1 gauss). which indicates distribution of the unpaired electrons over two or more molecules. It seems reasonable to
assume that the hydrogen Bridge protons of the structure
shown in Fig. 5 achieve considerable stabilization of the semiquinone radical anions formed in the reduction.
There are at present two contradictory theories about the
role of chlorophyll dimers in the oxidation of water, and
these enliven the interest in these aggregates.
According to KatzL3'I, a water-bridged chlorophyll dimer
(Chl HOH Chi) at the photosynthesis reaction center is linked
to the antennae-chlorophyll aggregate (Ch12), (see above) and
to an electron-acceptor and an electron-donor:
[ C h l HOH Chl]
Xo = e l e c t r o n donor
" s p e c i a l pair"
The assumption of a special chlorophyll dimer ("special
pair") at the reaction center is supported here again by the
observation of a particularly narrow ESR signal (line width
ca. 1 gauss) for the oxidized photoreaction center, and this
permits distribution of the unpaired electrons over at least
two chromophore molecules to be assumed. Irradiation of
this complex is held to lead, by way of the excited state,
to a new charge distribution in the dimer in accordance with:
Thereafter the chlorophyll radical cation oxidizes first Xe
and indirectly water, while the chlorophyll radical anion maintains the reductive part of the photosynthesis by way of Y.
Experimentally, both K ~ t z [ ~ and
' ] Dutton et a1.[461have
demonstrated the occurrence of the triplet state in photosynthesis, and this could indicate the above cation-anion radical
Whereas Katz bases his considerations on the unsymmetrical dimer of Fig. 7, F ~ n g 34J
[ ~and
assume a symmetrical sandwich dimer containing two water molecules, and
make the interesting speculation that its triplet state might
have an unusually long life. If this were so, the energy of
a singlet state from the antennae-chlorophyll could be added
to the energy of the relatively low-lying dimer-triplet state.
Thus, the oxidation of water could be effected in two steps
[eq. (b) and (c)], each involving one energy-rich charge-transfer
triplet state Chl?(H20)2ChI? without the necessity to invoke
further redox systems (e.g. the often postulated manganese
ion of higher oxidation numbers).
Angcw. Chrm. 1111 Ed. Enyl. f Vol. I5 ( 1 9 7 6 ) N o . I /
Cufrently attempts are being made throughout the world
to synthesize porphyrin aggregates in solids in order to cleave
water by sunlight in analogy to the natural process. A first,
hitherto unconfirmed, success has been announced by Wang,
who covered aluminum foil with ca. seventy monomolecular
layers of zinc porphyrin, dipped this deeply colored photoanode into an iron(II1) salt solution, and on irradiation
with red light obtained potentials ca. 1 volt greater than
that of a platinum electrode; two electrodes arranged one
behind the other led to evolution of oxygen from
If this experiment and its interpretation withstand critical
testing, then intensive investigations of this system with a
view to industrial utilization would appear attractive. Experiments with lipid membranes are already a center of interest.
If an aqueous solution of an oxidizing agent (e.g. Fe3+) is
separated by a bimolecular lipid membrane from a solution
of a reducing agent (e.g. Fe2+),the two solutions are stable
next to each other for a long time: no electron transport
takes place through the membrane. If, however, the membranes
contain oxidizable porphyrins, e. g. chlorophyll, then a slow
charge equalization between the two solutions can be observed,
and light accelerates this by many orders of magnitude. At
the same time photopotentials of about 100mV appear
between the membrane surfaces[481, these corresponding
approximately to the pH-gradients that arise in photosynthesis
on the membrane of vesicles of the photosynthetic system
(thylacoids). Very little is yet known about the importance
of porphyrin aggregation in this system.
Finally, an evolutionary-historical point may be noted. The
photosyntheses that we observe today are based on the reversible formation of energy-enriched and thus chemically extremely reactive molecular states (triplet states, radicals). In
monomolecular solutions, e. g. in chloroform, chlorophyll is
decomposed very rapidly on irradiation and oxidation. In
aggregates, however, the unpaired electron of the chromophore molecule is distributed over at least two partners,
greatly reducing the reactivity of the individual centers in
the molecule and thus protecting the system from destruction.
It is perfectly conceivable that in prebiotic time-and particularly then-organic molecules had a chance of surviving
and becoming components of biological systems if, first, they
could assume a useful role (here conversion of sunlight into
chemical energy), and, secondly, if they did not themselves
fall victim to their own functional reactivity. Other examples
could be seen in the protection of nucleic and amino acids,
which are sensitive to hydrolysis and redox systems, by integration into the complex structures of polymers (%aggregates).
7. Molecular Complexes of Porphyrins with Other
Natural Products
Although interest is nowadays concentrated on chlorophyll
dimers in connection with the reaction center for photosynthesis, aggregates with other natural n-systems have also been
studied. In particular, ff a v i n ~ [and
~ ~ Jq u i n o n e ~ [form
~ ~ ] with
chlorophyll charge-transfer complexes that may perhaps be
involved in the redox chains of photosynthesis. So far, however,
the structure is not known for any of these complexes, and
we shall therefore not treat them further here. However,
detailed CIDNP investigations have been reported for quinone
Complexes between paramagnetic metalloporphyrins and
steroids[’l] are of a different type. Hill et al. have investigated
these complexes by NMR methods similar to those used by
Katz for chlorophyll aggregates. A 5 x lo-* molar solution
of corticosterone (8) showed, for example, that on titration
with the cobalt(r1)-porphyrin ( 2 b ) strong paramagnetic shifts
of the protons on C1 > C2 > C3 > C4 > C11 occurred,
while the other signals were hardly shifted at all. As a result
of these findings and of systematic measurements of relative
line widths, a 1 : 1 molecular complex was postulated with
the following structural details. The steroid lies parallel to
the porphyrin and presents its unhindered a-side to the latter;
the mean separation between the two molecules is 5 to 8 A ,
with C9 of the steroid lying approximately over the center
of the porphyrin. The predominant bonding force between
the porphyrin as a prototype of an aromatic natural product
and the steroid with its rigid cycloalkene system is presumed
to be electrostatic-as the bonding forces described in Section
2. In the physiologically important iron@) complexes coordinated water could drastically alter the structure by the formation of hydrogen bonds and be the “specifying” factor. Such
complexes are of extreme interest in connection with the specific oxidation of steroids by heme catalysts and molecular
oxygen (see Section 9).
In this connection a remarkable observation on [2,2-bis(benzyloxycarbonyl)vinyl]porphyrins ( 9 a) and ( 9 b ) should be
noted. The phenyl group of the benzyl ester grouping lying
cis to the porphyrin occurs in solution exactly above the
center of the macrocycle; this can easily be demonstrated
by NMR spectroscopy of ( 9 b ) and can be ascribed to interactions of the type discussed in Section 2 (types a to c). X-Ray
structure analysis shows that the phenyl group in ( 9 a ) lies
perpendicular to the plane of the porphyrin (Fig. 14); this
was hardly to be expected in view of the current ideas on
interactions between n-systems[”]. Now it has been found,
in somewhat remote analogy to our case, by physical investigations of benzene, that this compound also is aggregated, and
indeed always in such a way that two benzene rings are
perpendicular to one another. This conformation is retained
even in the gas
The possible binding force has
been only tentatively indicated (quadrupole interactions?).
8. Oxygen Complexes of Iron(rr)-Porphyrins
This area has been studied unusually intensively during
the last five years and shows the miserable “signal-to-noise
ratio” typical of popular subjects. In other words, most of
the experimental papers on oxygen complexes are repetitive
in nature. In what follows we shall try to indicate the most
important lines of development.
Porphyrin plane
Fig. 15. The electron structure of the oxygen-bonding center in oxyhemoglobin
according t o Pauling.
C O-OC 7H7
(9a), M = C u , R = CHO
= Ni, R = H
(9b). M
Fig, 14. Molecular structure of the dibenzyl ester of porphyrin ( 9 a ) . The
phenyl group cis to the porphyrin sits perpendicularly almost directly above
the center of the porphyrin.
Many years ago Linus Pauling suggested the electron structure reproduced in Fig. 15 for the oxygen adduct of the heme
in hemoglobin (oxyhemoglobin, Hb02)[541.This structure
takes account of the diamagnetism of the H b 0 2 , explains
the increased acidity of the imidazole in HbOz (pK=6.8)
in comparison with free Hb (pK = 7.8), maintains the electron
neutrality of the central iron atom in heme, and permits
the following verifiable, specific predictions : the angle between
the Fe-0 and the 0-0 bond should be about 120”. The
Fe-0 bond should be as long as, or shorter than, the sum
of the covalent radii (=1.9&, and the oxygen atom should
show IR bands and 0-0 bond lengths corresponding approximately to a single bond. Furthermore, the oxygen molecule
should be polarized but not negatively charged in the sense
of a hyperoxide anion (Fe”’-OS)). Recently the first oxygen
complex of “picket-fence’’ iron porphyrin was obtained in
crystalline forn-such
a complex is sterically protected on
one side by the fence, and a provisional X-ray structure analysis, to be accepted with caution ( R =0.15), has been publ i ~ h e d [(Fig.
~ ~ I 16). This structure agrees beautifully with Pauling’s
the oxygen is indeed attached end-on
at an angle (aex,,
= 1367, and the Fe-0 and 0-0 separations
amount to 1.75 and 1.24i, respectively. However, the IR
stretching vibration of the 0-0 bond in the above oxygen
Angrw. Chuni. Int. Ed. Engl.
,’ Vol. 15 ( 1 9 7 6 ) N o . 1 I
complex is reputedly at 1385 cm-', which has not been
found for any other end-on oxygen complex; indeed, all the
complexes so far characterized as of this type show a band
near 11OOcm- 'I6'], which is close to that in potassium hyperoxide KO, (vO,=1145 cm-'). The absence of this band in
the picket-fence oxygen complex leaves open some doubt
about the molecular structure proposed[76!
The problem of the electronic structure of the active center
in H b 0 2 is, however, by no means resolved. The relative
stability of the iron(rr)-oxygen complex shown in Fig. 16
already provides important clues. Other iron(rr)-porphyrins,
Fig. 16. Provisional and still disputed [ 7 6 ] molecular structure of the iron(n)oxygen complex of the a,a,rr,a-atropic isomer of meso-tetrakis(o-pivalamido).
porphyrin. 'This compound is the first crystalline iron-porphyrin oxygen
complex. The structure corresponds to Paulincq's prediction.
e. g. protoheme ( ~ c ) [ ~ ~and
t e t r a p h e n ~ l h e m e [ ~form
~ ] , analogous complexes with oxygen in the presence of imidazole
derivatives below -40°C; at higher temperatures irreversible
oxidation to iron(lrr)-porphyrins sets in. This difference probably rests on the fact that the oxygen molecule in the complex
of Fig. 16 is sterically so shielded that the addition of a
second iron( rl)-porphyrin and subsequent , autoxidation
according to eq. (d) cannot occur[591(B =base, e. g. imidazole):
H b 0 2 + A r O - -+ HbO; +ArO'
HbOYt2HzO + HbOH+HzOz+OH-
The resistance of oxyhemoglobin to autoxidation thus apparently rests not on a special type of bonding of the oxygen
but rather on shielding of the bonding center against reducing
agents (including a second iron(l1)-porphyrin) and nucleophiles.
In Hilt's hands[631an important experiment has confirmed,
in particular, P a u h g ' s and Caughey's picture of oxyhemoglobin. Hill treated an iron(lr1)-porphyrin at low temperatures
(to prevent dimerization) with electrochemically produced
hyperoxide anions and obtained an oxygen complex whose
spectrum corresponded to a large extent with that of oxymyoglobin. It should also be pointed out that there is a paramagnetic analog of the diamagnetic HbO,: If the iron-porphyrin is
replaced by a cobalt-porphyrin, then that too adds oxygen;
in this case the oxygen molecule clearly exists as a hyperoxide
anion and can be identified by ESR s p e c t r o ~ c o p y651.
Summarizing, it can be stated that kinetic stabilization of
an iron-oxygen complex in the porphyrin series should succeed
when dimerization of two heme molecules can be prevented
in a hydrophobic, proton-free environment; this concept is
realized in the biological heme enzymes in which the porphyrin
is bound covalently or coordinatively in a hydrophobic matrix
(see for example Fig. 15). More recent experiments have shown
that free iron(il)-porphyrins or their oxygen complex can be
kept unchanged for as long as desired in synthetic hydrophobic
polymers[66,671; there, however, it is presumably the inflexibility of the synthetic polymers that makes the addition of
oxygen slower by many orders of magnitude than it is in
The occurrence and strength of the end-on bond of the
oxygen to heme depend largely on the rr-donor-acceptor properties of the axial ligands in tvans-positions. Oxygen complexes are stabilized considerably better by imidazole than
by e. g. piperidine or pyridine[681.If axial ligands are completely
absent, then 1 : 1 oxygen complexes with heme are formed
only in the crystalline state and their ESR spectra demonstrate
the occurrence of a high-spin iron(m)-porphyrin radical anion
[(g = 6) and (g = 2) signals]. The IR spectrum shows a stretching
vibration band at 1600cm-' that is very similar to the band
of the free oxygen molecule (vo,= 1555 cm-I), and the visible
electronic spectrum also indicates the occurrence of a rr-radical.
,Fe. N-6-
Nevertheless, the complex shown in Fig. 16 is also oxidized
rapidly in protonic solvents and more slowly in aprotic ones,
giving iron(lr1)-porphyrins, for which the proton-catalyzed
reaction (e) seems suitable:
+ H' + H 2 0 + Fe"'0H + H 2 0 2
In the above case the proton could be derived from the amide
groups with which the porphyrin is substituted.
Finally, Caughey showed that the oxygen in oxyhemoglobin
can be split off by anions (e.g. C1-, NS)[601or by reducing
agents (e.y. hydroquinone, salicylic acid)[6'I, affording hyperoxide anion, while the iron is oxidized to the trivalent state
[see, e.y. eq. (f) and (g)].
Angew. Cheni. Inr. Ed. Enql. f Vol. IS ( 1 9 7 6 ) N o . 11
o=o:. .
Fig. 17. Iron(ii)-porphyrinswithout axial ligands form, with oxygen, molecular
complexes in which the central iron ion probably transfers electrons to the
oxygen, and this oxygen then undergoes back-bonding to the porphyrin
ligands. Indications of this strncture are obtained mainly from IR and ESR
If the oxygen is pumped off, the iron@)-porphyrin is regenerated. Thus, the structure is revealed as probably a dimeric
heme in which two oxygen molecules are bonded by weak
donor-acceptor interactions to the positive charge centers of
the two iron(rr1) ions and to the negatively charged porphyrin
9. Reactivity of the Heme-bound Oxygen in vivo and
in vitro
Ascorbic acid, phenoxide ions, and other easily oxidized
substrates are rapidly oxidized even by the oxygen of oxyhemoglobin (Hb02)[61].Tryptophan-oxidase is a heme enzyme
that, similarly to hemoglobin, is built of four subunits and
catalyzes the addition of an oxygen atom to tryptophan (10).
The “hyperoxide anion” of HbOz is here presumably bonded
also to a copper ion, which could explain the special reactivity
The most reactive and thus the most interesting heme enzyme is cytochrome P 450, which introduces
oxygen atoms into unactivated CHZ groups, formally as in
Cytochrome P 450 acts as the end of a short electron-transport chain that does not form ATP, and with oxygen it probably forms an extremely electron-rich iron(I1)-hyperoxide
complex containing a cysteine-sulfur atom as the sixth ligand
( S - F e ” 4 ~
The oxygen is here so basic that
it deprotonates fl~orene[~’].
Other mechanisms are, however,
provisionally not excluded[72!
The attempts to imitate the catalytic activity of the heme
enzymes in vitro by means of metalloporphyrins have been
lamentably unsuccessful. Only radical chain peroxidations
occur, as for example in the reaction of cyclohexene ( 1 2 )
illustrated, this being catalyzed by some metallopor-
p h y r i n ~741.
[ ~Such
~ ~ reactions are, however, catalyzed by innumerable metal complexes; a peroxide formed primarily is
decomposed and probably no “oxygen activation” is involved,
so that the expensive heme analog has been wasted.
Catalysis by bismetal systems in which the oxygen molecule
is twice bonded and polarized is at the moment the most
hopeful route. For example, a pair often used in biology
is heme and copper ions bonded to a protein.
10. Prospects
The central problems for the future in this field are the
synthesis of suitable molecular complexes of chlorophyll and
porphyrins for conversion of light into redox energy (- membrane potential) and for specific catalytic oxidation of organic
substrates by molecular oxygen. Both these problem areas
are of extreme interest both scientifically and, in principle,
for industry. Among specific starting points the following
possibilities appear: syntheses and photochemical investigations of hydrated magnesium-porphyrin dimers (see Sections
3 and 6), construction of photoelectrodes from monomolecular
porphyrin layers or aggregates with micellar double
(see Section 6), and synthesis of porphyrins with intramolecularly defined ligand fields as well as covalently fixed electrondonors (see Section 9). These problems are currently under
worldwide study and important progress may be expected
in the near future.
In conclusion, let us return to Pauling’s remarks cited at
the beginning of this review. Investigations to determine structure and syntheses of specific molecular complexes do not,
of course, provide any “penetrating and reliable theory of
weak interactions”, but, in accord with one of the valued
traditions of organic chemistry, they enable general rules to
be derived and from these rules, prognoses. Specifically,
complex systems of varied utility may thereby be obtained.
“What the chemist does in a situation like this is to analyze
many molecules of a similar kind and get some empirical
rules. It is not very satisfactory from the point of view of
a physicist who is trying to understand from first principles.
But the problem of the chemist is different. He must try
to guess ahead of time what is going to happen with molecules
that haven’t been made yet, or which aren’t understood completeIy ... (Don’t forget that the reason a physicist can really
calculate from first principles is that he chooses only simple
problems)[75a1... and lo and behold !, the chemists are almost
The Gesellschaft fur Biotechnologische Forschung, under the
direction of Frau Dr. M.-R. Kula, has provided the best possible
support for the review and for our own experiments described
therein. 7he work has been financially supported by the Bundesminister fur Forschung und Technologie ( B M F T ) by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. Prof. Dr. H . Pommer of’ BASF placed 300 g of‘ precious
octaethylporphyrin at our disposal. Messrs. Hoechst (Frankfurt)
and Riedel-de Haen (Hanover) presented us with a thousand
liters of glacial acetic acid for the preparation of hemin, wherein
we were assisted by Messrs. Buchler (Braunschweig). Specialist
advice and willingness for friendly discussion from Prof: Dr.
H . H . Inhoffen, Dr. E . Lustig, Prof: Dr. H . Brockmann, Jr.,
Dr. J . Subramanian, Pro$ Dr. D. Mauzerall, and Prin.-Doz.
Dr. W S. Sheldrick were irreplaceable prerequisites for the
success of our own work. 7he experimental bases of the work
discussed in this review were provided by Dr. S . Besecke, Dr.
C. Mengersen, Dr. P. Wasser, Dr. L. Witte, and Dip1.-Chem.
R . Schlozer. X-Ray structure analyses were carried out by
Dr. W S . Sheldrick, G . Struckmeier, and U . Thewalt. To all
these Institutions and chemists I should like to express my
sincere thanks.
Received: 12th May, 1976 [A 134 IE]
German version: Angew. Chem. 88, 704 (1976)
Translated by Express Translation Service, London
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more likely.
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adduct, molecular, pigment, tetrapyrroles, complexes, oxygen
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