Synthesis of PDK, a Novel Porphyrin-Linked Dicarboxylate Ligand

Article abstract of DOI:10.1021/jo000502v

A novel trinucleating ligand system H₄(PDK), for porphyrin-based diamine bis(Kemp's triacid)-imide, was constructed by using two molecules of Kemp's triacid and one molecule of porphyrin as building blocks. The dimeso-substituted octaalkylporphyrin unit, carrying bromomethyl groups at the ortho positions of two trans-positioned meso-phenyl groups, was synthesized from (3,3′-diethyl-4,4′-dimethyl-2,2′-dipyrrolyl)methane and α-bromo-o-tolualdehyde. The structures of both of the two atropisomers (α,α- and α,β-) of bromoporphyrin, H₂(α,α-BP) and H₂(α,β-BP), were determined by X-ray crystallography, with the α,β-isomer as the free base form and the α,α-isomer as the zinc complex. Both the α,α- and α,β-isomers of the bromomethyl porphyrins were converted to their aminomethyl derivatives, H₂(α,α-AP) and H₂(α,β-AP), through the corresponding imidoporphyrin intermediates, H₂(α,α-IP) and H₂(α,β-IP), by the Gabriel synthesis. The α,α- and α,β- aminoporphyrins were coupled with Kemp's triacid anhydride-chloride to form H₄(α,α-PDK) and H₄(α,β-PDK), respectively. Unlike the α,β-isomer, the structure of which was determined by X-ray crystallography for the zinc complex, H₄(α,α-PDK) has a remarkable and complicated solvent-dependent ¹H NMR spectrum that suggests the existence of hydrogen bonding interactions between two convergent, tethered Kemp's triacid units, as predicted in a modeling study. The convergent feature is essential for the target ligand H₄(α,α-PDK) to form trinuclear metal complexes with a bis(carboxylato) dimetallic unit sitting above a metalloporphyrin ring.

Full text of DOI:10.1021/jo000502v

5298
J . Org. Chem. 2000, 65, 5298-5305
Syn th esis of P DK, a Novel P or p h yr in -Lin k ed Dica r boxyla te
Liga n d
Xiao-Xiang Zhang and Stephen J . Lippard*
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
lippard@lippard.mit.edu
Received April 3, 2000
A novel trinucleating ligand system H4(PDK), for porphyrin-based diamine bis(Kemp’s triacid)-
imide, was constructed by using two molecules of Kemp’s triacid and one molecule of porphyrin as
building blocks. The dimeso-substituted octaalkylporphyrin unit, carrying bromomethyl groups at
the ortho positions of two trans-positioned meso-phenyl groups, was synthesized from (3,3′-diethyl-
4,4′-dimethyl-2,2′-dipyrrolyl)methane and R-bromo-o-tolualdehyde. The structures of both of the
two atropisomers (R,R- and R,â-) of bromoporphyrin, H2(R,R-BP) and H2(R,â-BP), were determined
by X-ray crystallography, with the R,â-isomer as the free base form and the R,R-isomer as the zinc
complex. Both the R,R- and R,â-isomers of the bromomethyl porphyrins were converted to their
aminomethyl derivatives, H2(R,R-AP) and H2(R,â-AP), through the corresponding imidoporphyrin
intermediates, H2(R,R-IP) and H2(R,â-IP), by the Gabriel synthesis. The R,R- and R,â- aminopor-
phyrins were coupled with Kemp’s triacid anhydride-chloride to form H4(R,R-PDK) and H4(R,â-
PDK), respectively. Unlike the R,â-isomer, the structure of which was determined by X-ray
crystallography for the zinc complex, H4(R,R-PDK) has a remarkable and complicated solvent-
1
dependent H NMR spectrum that suggests the existence of hydrogen bonding interactions between
two convergent, tethered Kemp’s triacid units, as predicted in a modeling study. The convergent
feature is essential for the target ligand H4(R,R-PDK) to form trinuclear metal complexes with a
bis(carboxylato) dimetallic unit sitting above a metalloporphyrin ring.
In tr od u ction
ing ligands, has been demonstrated in recent years. The
ligand XDK, where H2(XDK) denotes m-xylenediamine
bis(Kemp’s triacid imide), is assembled by condensation
of two Kemp’s triacid anhydride-chloride molecules with
m-xylenediamine as a spacer.13 XDK has proved effective
for preparing dinuclear metal complexes including
non-heme diiron enzyme models.14-22 Several porphyrin
derivatives containing a Kemp’s triacid moiety have
been synthesized as host molecules for the purpose of
molecular recognition.23-26 The porphyrin unit in these
Metal ions play a significant role in biological trans-
formations, as established through the discovery of
numerous metalloenzymes and studies of their structures
and functions.1 Among the many chemical transforma-
tions mediated by metalloenzymes are multielectron
redox reactions such as the activation of O2. These
processes are among the most important and challenging
to understand. Structural and mechanistic information
obtained through a variety of spectroscopic and X-ray
crystallographic studies reveals that two or more metal
ions are required at the active centers of many multi-
electron redox enzymes. Significant examples include
heme-iron enzymes such as cytochrome P-4502,3 and
non-heme diiron enzymes such as soluble methane mono-
oxygenase (sMMO) and ribonucleotide reductase (RNR).4
These proteins have the ability to activate dioxygen
through multielectron reduction to accomplish substrate
oxidation, for example, the hydroxylation of alkanes.
Considerable progress has been made in the synthesis
of metalloporphyrins and dinuclear metal complexes
having structures analogous to those of the active sites
of cytochrome P-4505,6 and non-heme diiron enzymes.4,7,8
The utility of Kemp’s triacid9,10 as a building block, not
only for molecular receptors11,12 but also for metal chelat-
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10.1021/jo000502v CCC: $19.00 © 2000 American Chemical Society
Published on Web 07/21/2000

Synthesis of PDK
J . Org. Chem., Vol. 65, No. 17, 2000 5299
compounds served only as a spacer and/or a molecular
receptor site, however, and there is no prior example of
a multinuclear metal complex using a porphyrin-linked
Kemp’s triacid as the ligand.
In our continuing program to achieve a functional
model for sMMO,19,22,27,28 we were interested in designing
and constructing a system that can accommodate the
essential features of both the hydroxylase (MMOH) and
the reductase (MMOR) component proteins of sMMO.4,29
Substitution of the m-xylylenediamine spacer of XDK
with a porphyrin unit afforded a model that contains the
bis(carboxylato) diiron core of MMOH supported and
protected by a redox-active metalloporphyrin moiety for
assisting in the reductive activation of dioxygen, like the
function of MMOR. Although constructs linking a met-
alloporphyrin to a second metal-binding unit were
available30-36 as synthetic models related to cytochrome
c oxidase, there was no prior example of a triiron complex
having both heme and dinuclear non-heme iron features
in a molecule. Such an assembly facilitates comparison
of the active site chemistry in these two major metal-
loenzyme classes and also offers the potential to observe
new reactivities.
Resu lts a n d Discu ssion
Liga n d Design . The target ligand 5,15-bis(R-N-
(Kemp’s triacid imido)-o-tolyl)-2,8,12,18-tetraethyl-3,7,-
13,17-tetramethylporphyrin (H4(R,R-PDK)) was con-
structed from three pairs of building blocks, Kemp’s
triacid, R-bromo-o-tolualdehyde and dipyrrolylmethane
as indicated in the retrosynthetic analysis (Scheme 1).
The choice of (3,3′-diethyl-4,4′-dimethyl-2,2′-dipyrrolyl)-
methane for the porphyrin synthesis was based on
several considerations which are key elements in the
ligand design. Compared with tetraarylporphyrins, octa-
alkylporphyrins are more soluble in organic solvents,
allowing separation of atropisomers to be achieved on a
relatively large scale by column chromatography. The
isolated atropisomers are stable toward interconversion
in subsequent reaction steps owing to steric interactions
between the meso substituted phenyl rings and the
methyl groups on the pyrroles. Moreover, these ethyl and
methyl groups serve as convenient spectroscopic markers
To achieve this goal, we introduced37 the ligand PDK,
where H4(R,R-PDK) is R,R-5,15-bis(R-N-(Kemp’s triacid
imido)-o-tolyl)-2,8,12,18-tetraethyl-3,7,13,17-tetrameth-
ylporphyrin, derived from one porphyrin unit and two
convergent, tethered Kemp’s triacid units. The reaction
of H4(R,R-PDK) with FeBr2 in the presence of 2,6-lutidine
produced a novel triiron(II) complex [Fe3(R,R-PDK)(Lut)-
(Br)2(HBr)] in which a neutral HBr molecule resides in
the cavity housing three ferrous ions in an unprecedented
binding mode.37 A similar triiron(II) complex [Fe3(R,R-
PDK)(Lut)(I)2(HI)] with essentially the same geometry
was obtained when FeI2 was used as the iron source.
Here we report the design and synthetic details for pre-
paring this novel porphyrin-linked dicarboxylate ligand.
The chemistry used in several of the individual steps
is potentially applicable to the synthesis of related
molecules.
1
for product characterization by H NMR spectroscopy.
The synthetic route to H4(R,R-PDK) is outlined in
Scheme 2. The synthesis takes advantage of Rebek’s
well-tested coupling reaction between Kemp’s triacid
anhydride-chloride and a diamine, a procedure used in
the synthesis of H2(XDK).13 The porphyrin-based diamine
H2(AP) was obtained from the dibromo derivative H2(BP)
by Gabriel synthesis (Scheme 2). The dibromoporphyrin
H2(BP) was constructed from R-bromo-o-tolualdehyde
and (3,3′-diethyl-4,4′-dimethyl-2,2′-dipyrrolyl)methane as
illustrated.
Syn th esis of Bu ild in g Block s. There is only a single
report in the literature38 on the synthesis of the very
simple substituted aromatic aldehyde, R-bromo-o-tolual-
dehyde, a four-step route starting from o-tolualdehyde
with a total yield of only 5.6%. The number of steps and
poor yield of this synthesis are in striking contrast to the
one-step, high yield syntheses of both R-bromo-p-tolual-
dehyde39 and R-bromo-m-tolualdehyde40 from their nitrile
(26) Shipps, G., J r.; Rebek, J ., J r. Tetrahedron Lett. 1994, 35,
6823.
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(29) Gassner, G. T.; Lippard, S. J . Biochemistry 1999, 38, 12768.
(30) J u, T. D.; Ghiladi, R. A.; Lee, D.-H.; Strijdonck, G. P. F. v.;
Woods, A. S.; Cotter, R. J .; Victor G. Young, J .; Karlin, K. D. Inorg.
Chem. 1999, 38, 2244-2245.
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L. Chem. Commun. 1999, 2, 137-138.
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Commun. 1996, 629.
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Commun. 1995, 499.
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275, 949.
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(36) Karlin, K. D.; Nanthakumar, A.; Fox, S.; Murthy, N. N.; Ravi,
N.; Huynh, B. H.; Orosz, R. D.; Day, E. P. J . Am. Chem. Soc. 1994,
116, 4753.
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1998, 120, 10260.
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1977, 42, 369.
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5300 J . Org. Chem., Vol. 65, No. 17, 2000
Zhang and Lippard
Sch em e 1
by in situ oxidation with p-chloranil. Porphyrin H2(BP)
was obtained in good yield (45%) as a mixture of R,R-
and R,â-atropisomers, H2(R,R-BP) and H2(R,â-BP), in a
1
35:65 ratio as determined by H NMR integration. This
one-pot procedure only worked satisfactorily in a small-
scale synthesis, however. It gave a poor yield (∼10%) and
was difficult to purify when a relatively large-scale
synthesis was carried out, due to formation of a large
amount of polymeric material. A two-step approach41,44
was then employed with the isolation of the intermediate
porphyrinogen (Scheme 2). A gram scale synthesis of pure
porphyrin H2(BP) was achieved in 36% yield when
methanol was used as the solvent and p-toluenesulfonic
acid as the catalyst. The porphyrinogen intermediate
precipitated out from methanol and was easily isolated
by filtration. Subsequent DDQ oxidation afforded por-
phyrin H2(BP) as a 45:55 mixture of R,R- and R,â-
atropisomers, H2(R,R-BP) and H2(R,â-BP).
precursors by the controlled reduction with diisobutyl-
aluminum hydride (DIBAL-H). Initial attempts to pre-
pare R-bromo-o-tolualdehyde by DIBAL-H reductions of
R-bromo-o-tolunitrile gave poor yields (6-20%) with
difficulty of purification, owing to the formation of a large
amount of black polymeric material during the hydrolysis
step. A variety of conditions were then examined, includ-
ing different solvents, temperatures and workup proce-
dures. The black polymeric material presumably arises
from acidic polymerization of the unstable isoindole,
which is formed following by intramolecular nucleophilic
attack on the o-bromomethyl functional group by
the electron-rich nitrogen atom in the intermediate
(-CHdN--Al+R2). This reaction, which is obviously im-
possible in the reduction of R-bromo-p-tolunitrile and
R-bromo-m-tolunitrile, competes with hydrolysis for pro-
ducing the desired compound, R-bromo-o-tolualdehyde in
the case of R-bromo-o-tolunitrile. To avoid this undesired
intramolecular reaction, a different workup procedure
was employed. Specifically, the reaction mixture was
poured directly into a suspension consisting of ice and
an aqueous HBr solution instead of adding the acid into
the reaction mixture. The use of aqueous HBr solution
rather than HCl avoids formation of R-chloro-o-tolualde-
hyde obtained when the latter was used, presumably
resulting via a halide exchange reaction. With the new
workup procedure, the R-bromo-o-tolualdehyde building
block was synthesized as a clear brown liquid in 97%
yield (Scheme 2).
Both (3,3′-diethyl-4,4′-dimethyl-2,2′-dipyrrolyl)methane
and Kemp’s triacid anhydride-chloride were synthe-
sized by following modified literature precedues. The
former was prepared from commercially available
[5,5′-bis(ethoxycarbonyl)-3,3′-diethyl-4,4′-dimethyl-2,2′-di-
pyrrolyl]methane through hydrolysis and decarboxylation
steps41,42 (Scheme 2). Kemp’s triacid anhydride-chloride
was made from 1,3,5-cyclohexanetricarboxylic acid in a
four-step synthesis.9,10,13
Con str u ction of th e P or p h yr in Un it. Initially, the
bromoporphyrin, 5,15-bis(R-bromo-o-tolyl)-2,8,12,18-tetra-
ethyl-3,7,13,17-tetramethyl porphyrin, H2(BP), was syn-
thesized by a one-pot method43 without isolation of the
porphyrinogen cyclization intermediate. The reaction was
carried out at room temperature in anhydrous aceto-
nitrile with trichloroacetic acid as the catalyst, followed
The atropisomers were separated by flash chromatog-
raphy on a silica gel column, eluting with a solvent
mixture composed of 50% (v:v) of ethyl acetate and
1
hexane. The H NMR spectra of the H2(R,R-BP) and H2-
(R,â-BP) isomers displayed the same peak pattern. As a
result, the isomeric structures could not be determined
based on NMR spectroscopy. The higher Rf fraction of
the reaction mixture, which eluted first from the column,
was initially assigned as the R,â-isomer H2(R,â-BP) based
on its lower polarity. The more polar, lower Rf fraction,
which eluted with CH2Cl2 after the first fraction was
collected, was assigned as the R,R-isomer H2(R,R-BP).
Once the isolated atropisomers were available, however,
we found that they had very different solubility proper-
ties. Whereas the less polar, higher Rf fraction was quite
soluble in diethyl ether, the more polar, lower Rf fraction
was completely insoluble in the same solvent. This
solubility difference provided an easier separation method
for the two isomers, which could be later converted to
an equilibrium mixture at elevated temperature to
increase the yield of the desired isomer. The UV-vis
spectra of H2(R,R-BP) and H2(R,â-BP) are similar and
exhibit the characteristic porphyrin Soret and Q-bands.
Identification of atropisomers of porphyrins based on
polarity is commonly used in the literature, because of
their indistinguishable NMR spectra.42,44,45 The less polar
R,â-isomer is expected to elute first from silica gel using
organic solvents as the eluant, followed by the more polar
R,R-isomer. In this case, however, X-ray crystallography
proved such an assignment for H2(R,R-BP) and H2(R,â-
BP) based on polarity to be incorrect. Single crystals of
the lower Rf isomer suitable for X-ray diffraction were
grown by vapor diffusion of diethyl ether into a concen-
trated solution in CH2Cl2. The structure determination
(Table S1, Figure S1) surprisingly revealed the ether-
insoluble, lower Rf material to be the R,â- rather than
the R,R-isomer previously assigned on the basis of polar-
ity. The R,R-arrangement of the more soluble, higher Rf
isomer was also confirmed by an X-ray structural deter-
mination of its zinc complex [Zn(R,R-BP)] (Table S1,
Figure S2). This complex was prepared by reaction of the
free base porphyrin H2(R,R-BP) with zinc acetate in a
methanol/dichloromethane solvent mixture. Single crys-
tals of [Zn(R,R-BP)] suitable for X-ray study were ob-
(40) Bookser, B. C.; Bruice, T. C. J . Am. Chem. Soc. 1991, 113, 4208.
(41) Young, R.; Chang, C. K. J . Am. Chem. Soc. 1985, 107, 898.
(42) Sanders, G. M.; van Dijk, M.; van Veldhuizen, A.; van der Plas,
H. C. J . Org. Chem. 1988, 53, 5272.
(43) Osuka, A.; Nagata, T.; Kobayashi, F.; Maruyama, K. J . Hetero-
cycl. Chem. 1990, 27, 1657.
(44) Gunter, M. J .; Mander, L. N. J . Org. Chem. 1981, 46, 4792.
(45) Sanders, G. M.; van Dijk, M.; Machiels, B. M.; van Veldhuizen,
A. J . Org. Chem. 1991, 56, 1301.

Synthesis of PDK
J . Org. Chem., Vol. 65, No. 17, 2000 5301
Sch em e 2
tained by layering hexane onto a diethyl ether saturated
solution. The structure (Figure S2) demonstrates that
zinc is coordinated by a diethyl ether in an axial position
with a Zn-O distance of 2.20 Å. X-ray structure deter-
minations carried out for H2(R,R-BP) and [Zn(R,â-BP)]
also clearly revealed the orientations of two bromomethyl
groups, but the quality of the data sets prohibited
satisfactory refinements.
tion. Hydrazinolysis of the imidoporphyrin H2(IP) was
achieved with 98% hydrazine in THF at room tempera-
ture, followed by acidic decomposition of the intermediate
adducts.48 The corresponding aminoporphyrin H2(AP)
was obtained in good yields.
Cou p lin g of th e Am in op or p h yr in w ith Kem p ’s
Tr ia cid An h yd r id e Ch lor id e. The target ligand
isomers 5,15-bis(R-N-(Kemp’s triacid imido)-o-tolyl)-
2,8,12,18-tetraethyl-3,7,13,17-tetramethylporphyrin, H4-
(R,R-PDK) and H4(R,â-PDK), were synthesized by cou-
pling aminoporphyrin H2(AP) with Kemp’s triacid
anhydride-chloride. The reaction was performed in an-
hydrous pyridine in the presence of a catalytic amount
of DMAP according to the literature procedure developed
for the synthesis of H2(XDK).13 The presence of both
acidic and basic groups in H4(PDK) complicated in the
workup and purification procedures. Intensive efforts
were expended to find proper reaction conditions, workup
procedures and purification methods. The effective pro-
cedure is presented in the Experimental Section.
Although H4(R,â-PDK) could in its own right be an
interesting molecule, its synthesis was investigated as a
surrogate for the desired ligand H4(R,R-PDK) in this
project, considering the similarity of their syntheses. The
mono zinc complex of H4(R,â-PDK), [ZnH2(R,â-PDK)], was
prepared by reaction with zinc acetate. The structure of
[ZnH2(R,â-PDK)] determined by X-ray crystallography
(Table S1, Figure S3) revealed the zinc to have inserted
into the porphyrin ring. The two Kemp’s triacid units
orient in a manner such that the two carboxylic acids
are directed toward the center of the porphyrin unit. This
Con ver sion of th e Br om om eth ylp or p h yr in to th e
Am in om et h ylp or p h yr in . A classical Gabriel syn-
thesis46,47 was employed to convert the brominated por-
phyrins H2(R,R-BP) and H2(R,â-BP) to their corresponding
amino derivatives, 5,15-bis(R-amino-o-tolyl)-2,8,12,18-
tetraethyl-3,7,13,17-tetramethylporphyrin H2(R,R-AP)
and H2(R,â-AP), via the imidoporphyrin intermediates
5,15-bis(R-N-phthalimido-o-tolyl)-2,8,12,18-tetraethyl-
3,7,13,17-tetramethylporphyrin, H2(R,R-IP) and H2(R,â-
IP), as shown in Scheme 2. H2(BP) was allowed to react
with potassium phthalimide in anhydrous DMF to form
the imidoporphyrin H2(IP) by nucleophilic substitution.
Excess potassium phthalimide was used to drive the
reaction to completion. Otherwise, a significant amount
of monosubstituted compound was obtained. Exclusion
of water from the reaction mixture by using anhydrous
DMF and well-dried reactants was critical for the
successful transformation. In the presence of water,
the benzyl bromide hydrolyzes to benzyl alcohol. The
reaction was carried out at a modest temperature (80 °C)
since higher temperatures led to significant isomeriza-
(46) Gibson, M. S.; Bradshaw, R. W. Angew. Chem., Int. Ed., Engl.
1968, 7, 919.
(47) Sheehan, J . C.; Bolhofer, W. A. J . Am. Chem. Soc. 1950, 72,
2786.
(48) Nigh, W. G. J . Chem. Edu. 1975, 52, 670.

5302 J . Org. Chem., Vol. 65, No. 17, 2000
Zhang and Lippard
F igu r e 1. NMR spectra for H4(R,R-PDK) in CDCl3 (a) before and (b) after addition of a small amount of CD3OD.
feature is essential for the H4(R,R-PDK) isomeric ligand
to form trinuclear metal complexes having a bis(carboxyl-
ato) dimetallic unit situated above the metalloporphyrin
ring. The Kemp’s triacid units in [ZnH2(R,â-PDK)],
however, are not located directly above the porphyrin unit
(Figure S3). Such a structure differs from that suggested
by 1H NMR for solutions of this complex. Compared with
H2(XDK),13 the Kemp’s triacid unit proton resonances in
1
the H NMR spectrum of [ZnH2(R,â-PDK)] shift signifi-
cantly to higher fields. As an example, the two single
methyl peaks shift from 1.32 and 1.30 ppm in H2(XDK)13
to 1.02 and 0.76 ppm in [ZnH2(R,â-PDK)]. These high
field shifts result from the porphyrin ring current,
F igu r e 2. Structure of H4(R,R-PDK) generated from energy
suggesting that the Kemp’s triacid units are located
above the porphyrin ring. The discrepancy between the
X-ray and solution NMR structures is a result of inter-
molecular hydrogen bonding interactions in the solid
state. As shown in the crystal packing diagram (Figure
S4), one Kemp’s triacid unit of molecule A is oriented
toward the zinc center of molecule B through a hydrogen
bonding interaction between imido carbonyl and carbox-
ylic acid oxygen atoms. As a result, the Kemp’s acid
units are forced to bend away from the center of the
porphyrin ring.
Unlike H4(R,â-PDK), H4(R,R-PDK) has a remarkable
and complicated solvent-dependent 1H NMR spectral
behavior. Whereas the 1H NMR spectrum of H4(R,R-PDK)
in CD3OD is well understood and consistent with its
expected structure, the spectrum in CDCl3 displays a
complicated multiple peak pattern in the expected chemi-
cal shift range along with peaks in high field region, δ
(ppm) -0.23 (d), -0.54 (d), -1.72 (s), -1.96 (s), -2.36
(s), -2.52 (m), -4.62 (m), -5.67 (d) (Figure 1). Upon
addition of a small amount of CD3OD, however, the
spectrum converts to one identical to that in CD3OD
(Figure 1). This transformation is ascribed to solvent-
dependent hydrogen bonding interactions between the
two carboxylic acids. In nonpolar solvents such as CDCl3,
such hydrogen bonding is favored and brings the two
Kemp’s acid units right above the porphyrin ring. As a
result, the porphyrin distorts from a planar into a ruffled
conformation, as indicated by a structure generated from
energy minimization by computer modeling (Figure 2).
The interaction, however, is disrupted by solvents such
minimization by computer modeling.
as CD3OD, which are capable of forming hydrogen bonds
with the carboxylic acid. The complicated multiple-peak
pattern observed in CDCl3 is therefore ascribed to the
broken symmetry. Due to strong ring current effects
imposed by the porphyrin unit, the resonances of the
Kemp’s triacid units appeared at high field. A similar
NMR phenomenon was also observed for the zinc complex
of H4(R,R-PDK), [ZnH2(R,R-PDK)]. The existence and
interconversion of multiple conformations may be par-
tially responsible for our inability to grow single crystals
of H4(R,R-PDK) and [ZnH2(R,R-PDK)] suitable for X-ray
structural determination. The proposed convergent struc-
ture of H4(R,R-PDK), however, was unambiguously con-
firmed through X-ray determinations of a variety of
trinuclear complexes49 including the reported triiron(II)
[Fe3(R,R-PDK)(Lut)(X)2(HX)] (X ) Br, I) species.37
Su m m a r y a n d Con clu sion
A novel trinuclear ligand system H4(PDK) was de-
signed and prepared by a multistep synthesis from three
basic building blocks, each of which was efficiently
synthesized from commercially available materials. A key
workup procedure was developed for the controlled
reduction of R-bromo-o-tolunitrile to form R-bromo-o-
tolualdehyde in high yield. The intermediate bromopor-
phyrin was synthesized in good yield, and convenient
(49) Zhang, X.-X.; Lippard, S. J . Unpublished results.

Synthesis of PDK
J . Org. Chem., Vol. 65, No. 17, 2000 5303
(3,3′-Dieth yl-4,4′-d im eth yl-2,2′-d ip yr r olyl)m eth a n e. The
preparation of (3,3′-diethyl-4,4′-dimethyl-2,2′-dipyrrolyl)methane
was accomplished from commercially available [5,5′-bis(ethoxy-
carbonyl)-3,3′-diethyl-4,4′-dimethyl-2,2′-dipyrrolyl]methane
through hydrolysis and decarboxylation in the presence of
KOH in 95% ethanol under a refluxing Ar atmosphere.41,42 It
was obtained as a light tan crystalline material in 94% yield:
1H NMR (CDCl3), δ (ppm) 7.26 (br s, 2H, NH), 6.35 (m, 2H,
5-H), 3.79 (s, 2H, -CH2-), 2.47 (q, 4H, -CH2CH3), 2.03 (s,
6H, -CH3), 1.12 (t, 6H, -CH2CH3).
cis,cis-1,3,5-Tr im et h ylcycloh exa n e-1,3-a n h yd r id e-5-
Acid Ch lor id e (Kem p ’s Tr ia cid An h yd r id e-Ch lor id e).
Kemp’s triacid anhydride-chloride was formed from the reac-
tion of Kemp’s triacid with SOCl2 by following the literature
procedure.9,10,13
5,15-Bis(r-br om o-o-tolyl)-2,8,12,18-tetr a eth yl-3,7,13,17-
tetr a m eth ylp or p h yr in , H2(BP ). Two methods were used for
the synthesis of bromoporphyrin H2(BP). In method A,43 the
porphyrin was prepared by a one-pot method without isolation
of the cyclized intermediate porphyrinogen. In method B,41,44
the porphyrin was synthesized in two steps with the isolation
of the intermediate porphyrinogen.
Meth od A. R-Bromo-o-tolualdehyde (246 mg, 1.24 mmol)
and (3,3′-diethyl-4,4′-dimethyl-2,2′-dipyrrolyl)methane (185
mg, 1.24 mmol) were dissolved in anhydrous acetonitrile (20
mL). The resulting solution was kept in the dark, by wrapping
the flask with an aluminum foil, and maintained under an
argon atmosphere. Trichloroacetic acid (35 mg, 0.21 mmol) was
added. The reaction mixture was stirred at room temperature
for 5 h. A solution of p-chloranil (500 mg, 2.0 mmol) in THF
(20 mL) was added. The mixture was stirred at room temper-
ature for another 6.5 h. Removal of the solvent gave a residue.
The raw material was purified by flash column chromatogra-
phy (silica gel, CH2Cl2) to afford bromoporphyrin H2(BP)
(227 mg, 45% yield) as a mixture of R,R- and R,â-atropisomers
(H2(R,R-BP) and H2(R,â-BP)) in a ratio of 35 to 65.
Meth od B. R-Bromo-o-tolualdehyde (1.35 g, 6.77 mmol) and
(3,3′-diethyl-4,4′-dimethyl-2,2′-dipyrrolyl)methane (1.56 g, 6.77
mmol) were dissolved in methanol (80 mL). The solution was
deoxygenated by bubbling with argon for 30 min. p-Toluene-
sulfonic acid monohydrate (0.36 g, 1.9 mmol) was added. After
stirring for 15 min under argon, the mixture was allowed to
stand in the dark first at room temperature for 6 h and then
at 4 °C for 16 h. The resulting yellow precipitate was collected
by filtration and washed with cold methanol to give the crude
porphyrinogen. This material (1.2 g, 1.46 mmol) was dissolved
in dry THF (100 mL) and then treated with a solution of 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ, 1.5 g, 6.61 mmol)
in dry THF (20 mL). The resulting dark suspension was stirred
at room temperature for 3 h. After the solvent was removed
by rotary evaporation, the solid residue was treated with
10% aqueous NaOH solution to dissolve the hydroquinone.
The remaining precipitates were collected by filtration and
washed thoroughly with water. The solid was then dissolved
in CH2Cl2 and washed once with 1 N NaHCO3 and twice with
water. The organic layer was dried over anhydrous Na2SO4.
Evaporation of the solvent gave a purple solid which was
purified by flash column chromatography (silica gel, CH2Cl2)
to afford bromoporphyrin H2(BP) (1.0 g, 36% yield) as a
mixture of R,R- and R,â-atropisomers (H2(R,R-BP) and H2(R,â-
BP) in a ratio of 45 to 55.
separation procedures of the atropisomers were devel-
oped. Continuing isomerization at elevated temperature
can be used to increase the yield of a desired isomer.
The unambiguous structural determinations of both
atropisomers by X-ray crystallography call in to question
the validity of commonly used polarity arguments to
assign stereochemistry. The structure of [ZnH2(R,â-PDK)]
determined by X-ray crystallography differs from that
suggested by NMR spectroscopy because of crystal pack-
ing. The remarkable and complicated solvent-dependent
1H NMR properties of H4(R,R-PDK) suggest the existence
of hydrogen bonding interactions between two conver-
gent, tethered Kemp’s triacid units, as supported in a
computer modeling study. This essential feature makes
H4(R,R-PDK) well suited to form trinuclear metal com-
plexes having a bis(carboxylato) dimetallic unit situated
above the metalloporphyrin base. By following the pro-
cedure described in this report, several grams of H4(R,R-
PDK) can be isolated in ca. 17% overall yield in a period
of 2 weeks.
Exp er im en ta l Section
Gen er a l P r oced u r es a n d Meth od s. Solvents were dried
and distilled under nitrogen by standard procedures.50 Unless
otherwise noted, reagents were obtained from commercial
suppliers and used as received. All manipulations and reac-
tions were carried out under an inert atmosphere in a Vacuum
Atmospheres glovebox or by using standard Schlenk tech-
niques. 1H NMR spectra were recorded on a Bruker AC-250
MHz spectrometer. All spectra were referenced using the
residual solvent peak as an internal standard (methanol-d4,
δ ) 4.87; chloroform-d1, δ ) 7.24). UV-vis spectra were
recorded with a Varian Cary 1E spectrophotometer. FTIR
spectra in the range 4000-400 cm-1 were obtained and
manipulated by using a Bio-Rad SPC3200 FTIR instrument,
or a Bio-Rad FTS 135 spectrometer. Samples were prepared
as either KBr pellets or Nujol mulls or studied in neat forms.
Fast atom bombardment (FAB) mass spectroscopy was per-
formed in the MIT Department of Chemistry Instrumentation
Facility with the use of m-nitrobenzyl alcohol as the matrix
and a parallel run of cesium rubidium iodide for the reference.
r-Br om o-o-tolu a ld eh yd e. After being purged with argon
for 30 min, a solution of R-bromo-o-tolunitrile (5.0 g, 25.5
mmol) in dried CH2Cl2 (75 mL) was cooled in an ice-water
bath and maintained under an argon atmosphere. A solution
of diisobutyl aluminum hydride (DIBAL-H, 1.0 M, 26.0 mL,
26.0 mmol) in heptane was added in a dropwise manner over
a period of 30 min. The resulting solution was then allowed
to warm slowly to room temperature with stirring in a period
of 3 h by removing the ice-water bath. The resulting reaction
mixture was cooled again with an ice-bath, and then directly
poured into a 1000 mL beaker containing ice (100 g) and a
precooled HBr aqueous solution (6.0 N, 100 mL). The resulting
mixture was vigorously stirred for 1 h without darkening, and
then extracted with CH2Cl2 three times (100 mL twice; 50 mL
once). The CH2Cl2 solutions were combined and washed with
1 N NaHCO3 (once) and H2O (twice), and then dried over
anhydrous Na2SO4. Evaporation of solvent afforded R-bromo-
o-tolualdehyde (4.9 g, 97% yield) as a clear brown liquid with
high purity. Further purification can be carried out by flash
column chromatography (silica gel, CH2Cl2): 1H NMR (CDCl3),
Sep a r a tion of Atr op isom er s. The mixture of the isomers
was separated by flash column chromatography (silica gel,
ethyl acetate and/hexane (v/v) ) 1/1). The R,R-isomer H2(R,R-
BP) eluted first, followed by the R,â-isomer H2(R,â-BP) with
CH2Cl2 as eluting solvent. Alternatively, the mixture of
isomers was treated with diethyl ether and separated by
filtration. The undissolved solid was identified as the R,â-
isomer H2(R,â-BP). The filtrate was concentrated to give the
R,R-isomer H2(R,R-BP). H2(R,R-BP): 1H NMR (CDCl3), δ (ppm)
3
δ (ppm): 10.21 (s, 1H, CHO), 7.80 (dd, 1H, J H-H ) 7.2 Hz,
4J H-H ) 1.7 Hz, phenyl), 7.54 (td, 1H, 3J H-H ) 7.2 Hz, 4J H-H
)
3
4
1.7 Hz, phenyl), 7.47 (td, 1H, J H-H ) 7.2 Hz, J H-H ) 1.7 Hz,
phenyl), 7.44 (dd, 1H, 3J H-H ) 7.2 Hz, 4J H-H ) 1.7 Hz, phenyl),
4.91 (s, 2H, -CH2Br); IR (neat) υCO 1700 cm-1; HRMS-EI (M+)
calcd for C8H7BrO 197.96803, found 197.96795.
3
4
10.25 (s, 2H, methine), 8.14 (dd, 2H, J H-H ) 7.3 Hz, J H-H
)
1.3 Hz, phenyl), 7.94 (dd, 2H, 3J H-H ) 7.3 Hz, 4J H-H ) 1.3 Hz,
phenyl), 7.84 (td, 2H, 3J H-H ) 7.3 Hz, 4J H-H ) 1.3 Hz, phenyl),
3
4
7.72 (td, 2H, J H-H ) 7.3 Hz, J H-H ) 1.3 Hz, phenyl), 4.10 (s,
4H, -CH2Br), 4.03 (q, 8H, 3J H-H ) 7.5 Hz, -CH2CH3), 2.49 (s,
(50) Perrin, D. D.; Perrin, D. R.; Armarego, W. L. Purification of
Laboratory Chemicals; Pergamon Press: Oxford, 1980.

5304 J . Org. Chem., Vol. 65, No. 17, 2000
Zhang and Lippard
3
3
12H, -CH3), 1.77 (t, 12H, J H-H ) 7.5 Hz, -CH2CH3), -2.37
12H, -CH3), 1.77 (t, 12H, J H-H ) 7.5 Hz, -CH2CH3), -2.43
(br s, 2H, -NH); UV-vis (CH2Cl2), λmax (nm) 628, 575, 543,
508, 409; HRMS-FAB (M+) calcd for C62H56N6O4 948.43631,
found 948.43661.
(br s, 2H, -NH); UV-vis (CH2Cl2), λmax (nm) 626, 575, 542,
507, 409; HRMS-FAB (M+) calcd for C46H48Br2N4 814.22457,
found 814.22360. H2(R,â-BP): 1H NMR (CDCl3) δ (ppm) 10.22
3
4
(s, 2H, methine), 8.02 (dd, 2H, J H-H ) 7.2 Hz, J H-H ) 1.2
r,â-5,15-Bis(r-N-p h t h a lim id o-o-t olyl)-2,8,12,18-t et r a -
eth yl-3,7,13,17-tetr a m eth ylp or p h yr in , H2(r,â-IP ). The R,â-
imidoporphyrin H2(R,â-IP) was prepared from the reaction of
R,â-bromoporphyrin H2(R,â-BP) with potassium phthalimide
by a procedure analogous to that given for R,R-imidoporphyrin
H2(R,R-IP): 1H NMR (CDCl3), δ (ppm) 10.17 (s, 2H, methine),
8.05-7.34 (m, 16H, phenyl), 4.55 (s, 4H, -CH2N<), 3.99
3
4
Hz, phenyl), 7.95 (dd, 2H, J H-H ) 7.2 Hz, J H-H ) 1.2 Hz,
phenyl), 7.83 (td, 2H, 3J H-H ) 7.2 Hz, 4J H-H ) 1.2 Hz, phenyl),
3
4
7.67 (td, 2H, J H-H ) 7.2 Hz, J H-H ) 1.2 Hz, phenyl), 4.20 (s,
3
4H, -CH2Br), 4.00 (q, 8H, J H-H ) 7.5 Hz, -CH2CH3), 2.47 (s,
3
12H, -CH3), 1.75 (t, 12H, J H-H ) 7.5 Hz, -CH2CH3), -2.36
(br s, 2H, -NH); UV-vis (CH2Cl2), λmax (nm) 626, 574, 541,
507, 409.
3
(q, 8H, J H-H ) 7.5 Hz, -CH2CH3), 2.54 (s, 12H, -CH3), 1.78
3
r,r-[5,15-Bis(r-b r om o-o-t olyl)-2,8,12,18-t e t r a e t h yl-
3,7,13,17-tetr a m eth yl p or p h yr in ]zin c(II), [Zn (r,r-BP )]. A
saturated solution of zinc acetate dihydrate, Zn(OAc)2‚2H2O,
(54 mg, 0.25 mmol), in methanol was added to a solution
of R,R-bromoporphyrin H2(R,R-BP) (20 mg, 0.025 mmol) in
CH2Cl2 (5.0 mL). The resulting mixture was stirred in the dark
at room temperature. The reaction was monitored by TLC
using CH2Cl2 as a developing solvent. After 3 h, the solvents
were removed and the residue was extracted with CHCl3. The
CHCl3 solution was washed once with 1N NaHCO3 and twice
with water. After the organic layer was dried over anhydrous
Na2SO4, the solvent was evaporated to give a pink-purple solid
which was purified by flash column chromatography (silica gel,
CH2Cl2) to afford [Zn(R,R-BP)] (17 mg, 80% yield): 1H NMR
(t, 12H, J H-H ) 7.5 Hz, -CH2CH3), -2.42 (br s, 2H, -NH);
UV-vis (CH2Cl2), λmax (nm) 628, 575, 543, 508, 409.
r,r-5,15-B is (r-a m in o -o-t o ly l)-2,8,12,18-t e t r a e t h y l-
3,7,13,17-tetr a m eth ylp or p h yr in , H2(r,r-AP ). An excess
amount of 98% hydrazine (1 mL) was added to a solution of
R,R-imidoporphyrin H2(R,R-IP) (220 mg, 0.23 mmol) in THF
(20 mL). The resulting mixture was stirred at room temper-
ature in the dark for 17 h. The solvent and excess hydrazine
were removed in a vacuum. The residue was treated with 6 N
HCl aqueous solution (40 mL) and heated to reflux at 95 °C
for 1 h. The precipitates formed were removed by filtration
and the filtrate, cooled in an ice-water bath, was made
alkaline with concentrated aqueous NaOH solution until a
precipitate formed. The aqueous suspension was then ex-
tracted with CHCl3 and washed three times with brine. The
organic layer was dried over anhydrous Na2SO4 and concen-
trated in a vacuum to afford R,R-aminoporphyrin H2(R,R-AP)
(140 mg, 88% yield): 1H NMR (CDCl3), δ (ppm) 10.24 (s, 2H,
(CDCl3), δ (ppm) 10.18 (s, 2H, methine), 8.15 (dd, 2H, 3J H-H
7.4 Hz, 4J H-H ) 1.4 Hz, phenyl), 7.92 (dd, 2H, 3J H-H ) 7.4 Hz,
)
4J H-H ) 1.4 Hz, phenyl), 7.83 (td, 2H, 3J H-H ) 7.4 Hz, 4J H-H
)
3
4
1.4 Hz, phenyl), 7.71 (td, 2H, J H-H ) 7.4 Hz, J H-H ) 1.4 Hz,
3
3
phenyl), 4.01 (s, 4H, -CH2Br), 3.99 (q, 8H, J H-H ) 7.5 Hz,
methine), 8.05 (d, 2H, J H-H ) 7.3 Hz, phenyl), 7.85 (d, 2H,
3
3
-CH2CH3), 2.44 (s, 12H, -CH3), 1.75 (t, 12H, J H-H ) 7.5 Hz,
3J H-H ) 7.3 Hz, phenyl), 7.82 (t, 2H, J H-H ) 7.3 Hz, phenyl),
3
3
-CH2CH3); UV-vis (CH2Cl2), λmax (nm) 575, 538, 411.
r,â-[5,15-Bis(r-b r om o-o-t olyl)-2,8,12,18-t e t r a e t h yl-
3,7,13,17-tetr am eth ylpor ph yr in ]zin c(II), [Zn (r,â-BP )]. The
zinc complex of R,â-bromoporphyrin [Zn(R,â-BP)] was prepared
from the reaction of R,â-bromoporphyrin H2(R,â-BP) with zinc
acetate dihydrate by a procedure analogous to that given for
zinc complex of the R,R-bromoporphyrin [Zn(R,R-BP)]: 1H
NMR (CDCl3), δ (ppm) 10.17 (s, 2H, methine), 8.04 (dd, 2H,
7.69 (t, 2H, J H-H ) 7.3 Hz, phenyl), 4.02 (q, 8H, J H-H ) 7.5
Hz, -CH2CH3), 3.45 (br s, 4H, -CH2NH2), 2.47 (s, 12H, -CH3),
3
1.77 (t, 12H, J H-H ) 7.5 Hz, -CH2CH3), 1.20 (br s, 4H,
-CH2NH2), -2.36 (br s, 2H, -NH); UV-vis (CH2Cl2), λmax (nm)
654, 627, 575, 542, 507, 409; HRMS-FAB (M+) calcd for
C
46H52N6 688.42535, found 688.42561.
r,â-5,15-B is (r-a m in o -o-t o ly l)-2,8,12,18-t e t r a e t h y l-
3,7,13,17-t et r a m et h ylp or p h yr in , H2(r,â-AP ). The R,â-
aminoporphyrin H2(R,â-AP) was prepared from the reaction
of R,â-imidoporphyrin H2(R,â-IP) and 98% hydrazine by the
same procedure given for R,R-aminoporphyrin H2(R,R-AP): 1H
NMR (CDCl3), δ (ppm) 10.22 (s, 2H, methine), 7.96 (d, 2H,
3J H-H ) 7.6 Hz, J H-H ) 1.3 Hz, phenyl), 7.95 (dd, 2H, J H-H
4
3
4
3
) 7.6 Hz, J H-H ) 1.3 Hz, phenyl), 7.83 (td, 2H, J H-H ) 7.6
Hz, 4J H-H ) 1.3 Hz, phenyl), 7.68 (td, 2H, 3J H-H ) 7.6 Hz, 4J H-H
3
) 1.3 Hz, phenyl), 4.14 (s, 4H, -CH2Br), 3.99 (q, 8H, J H-H
)
)
3
3
7.5 Hz, -CH2CH3), 2.43 (s, 12H, -CH3), 1.75 (t, 12H, J H-H
3J H-H ) 7.3 Hz, phenyl), 7.84 (d, 2H, J H-H ) 7.3 Hz, phenyl),
3
3
7.5 Hz, -CH2CH3); UV-vis (CH2Cl2), λmax (nm) 575, 538, 411.
Con ver sion of H2(r,â-BP ) t o H2(r,r-BP ) b y Th er m a l
Isom er iza tion . A portion of H2(R,â-BP) (385 mg) was dis-
solved in a mixture of CHCl3 (50 mL) and xylenes (100 mL).44
The solution was distilled under a stream of Ar until the liquid
temperature reached 137 °C. The distillation head was then
replaced by a reflux condenser, and the solution was heated
to reflux under Ar and protected from light for 35 h. After the
solvent was removed by rotary evaporation, the residue was
dissolved in a minimum amount of CH2Cl2 and layered with
Et2O to effect the precipitation of H2(R,â-BP). The precipitate
collected by filtration was mainly H2(R,â-BP), which can be
further converted to H2(R,R-BP) by repeating the above
procedure. The filtrate was concentrated and was further
purified by flash column chromatography to give pure H2(R,R-
BP) (170 mg).
7.78 (t, 2H, J H-H ) 7.3 Hz, phenyl), 7.65 (t, 2H, J H-H ) 7.3
3
Hz, phenyl), 4.01 (q, 8H, J H-H ) 7.5 Hz, -CH2CH3), 3.52 (br
3
s, 4H, -CH2NH2), 2.46 (s, 12H, -CH3), 1.76 (t, 12H, J H-H
)
7.5 Hz, -CH2CH3), 1.21 (br s, 4H, -CH2NH2), -2.37 (br s, 2H,
-NH); UV-vis (CH2Cl2), λmax (nm) 654, 627, 575, 542, 507,
409.
r,r-5,15-Bis(r-N-(Kem p’s tr iacid im ido)-o-tolyl)-2,8,12,18-
tetr a eth yl-3,7,13,17-tetr a m eth ylp or p h yr in , H4(r,r-P DK).
In a 100 mL three-neck flask equipped with a condenser,
H2(R,R-AP) (441 mg, 0.640 mmol), Kemp’s triacid anhydride
chloride (331.2 mg, 1.280 mmol), 2,6-di-tert-butyl pyridine (612
mg, 3.20 mmol) and DMAP (7.82 mg, 0.064 mmol) were
dissolved in anhydrous toluene (20 mL). After it was purged
with Ar for 30 min, the reaction solution was heated at 90 °C
with protection from light for 18 h. The reaction mixture was
cooled to room temperature, treated with CHCl3 (50 mL), and
washed with HCl solution (100 mL, 1.2 N). The water phase
was extracted further twice with CHCl3 until the CHCl3 phase
was colorless. The combined greenish CHCl3 extracts were
washed three times with water until the color changed to red
purple and the aqueous phase was neutral (pH ∼ 6-7). After
drying over anhydrous Na2SO4, the organic layer was concen-
trated and subjected to flash column chromatography (silica
gel, THF) to afford purple H4(R,R-PDK) (585 mg, 81%): 1H
NMR (250 MHz, CD3OD, 296 K), δ (ppm) porphyrin unit:
r,r-5,15-Bis(r-N-p h t h a lim id o-o-t olyl)-2,8,12,18-t et r a -
eth yl-3,7,13,17-tetr a m eth ylp or p h yr in , H2(r,r-IP ). Portions
of H2(R,R-BP) (413 mg, 0.51 mmol) and potassium phthalimide
(446 mg, 2.44 mmol) were dissolved in anhydrous DMF (50
mL). The resulting solution was heated under argon at 80 °C
for 16 h. DMF was removed, and the residue was dissolved in
CHCl3 and washed once with 1N NaHCO3 and three times
with water. After the organic layer was dried over anhydrous
Na2SO4 and concentrated in a vacuum, the residue was
purified by flash column chromatography (silica gel, ethyl
acetate/hexane (v/v) ) 1/2) to afford R,R-imidoporphyrin
H2(R,R-IP) (400 mg, 83% yield): 1H NMR (CDCl3), δ (ppm)
10.14 (s, 2H, methine), 8.02-7.33 (m, 16H, phenyl), 4.53 (s,
4H, -CH2N<), 3.98 (q, 8H, 3J H-H ) 7.5 Hz, -CH2CH3), 2.53 (s,
3
10.26 (s, 2H, methine), 7.78 (d, 2H, J H-H ) 7.2 Hz, phenyl),
3
3
7.75 (pseudo-t, 2H, J H-H ) 7.45 Hz, J H-H ) 7.6 Hz, phenyl),
3
3
7.62 (pseudo-t, 2H, J H-H ) 7.2 Hz, J H-H ) 7.45 Hz, phenyl),
3
7.19 (d, 2H, J H-H ) 7.6 Hz, phenyl), 4.49 (s, 4H, -CH2N<),
3
4.02 (q, 8H, J H-H ) 7.5 Hz, -CH2CH3), 2.53 (s, 12H, -CH3),

Synthesis of PDK
J . Org. Chem., Vol. 65, No. 17, 2000 5305
3
1.78 (t, 12H, J H-H ) 7.5 Hz, -CH2CH3), Kemp’s triacid unit:
(13 mg, 85%). Recrystallization from vapor diffusion of pentane
into a concentrated solution of [ZnH2(R,â-PDK)] in ethyl
acetate at room temperature in a period of two weeks afforded
single crystals which appeared suitable for X-ray crystal-
2
2.15 (d, 4H, J H-H ) 14.0 Hz, cyclohexyl-H), 1.96 (d, 2H,
2J H-H ) 13.0 Hz, cyclohexyl-H), 1.31 (d, 2H, J H-H ) 13.0 Hz,
2
cyclohexyl-H), 0.89 (d, 4H, 2J H-H ) 14.0 Hz, cyclohexyl-H), 1.02
(s, 12H, -CH3), 0.75 (s, 6H, -CH3); 1H NMR (CDCl3), very
complicated peaks in the range between 11 and 0 ppm plus
high field peaks, δ (ppm) -0.23 (d), -0.54 (d), -1.72 (s), -1.96
(s), -2.36 (s), -2.52 (m), -4.62 (m), -5.67 (d); UV-vis (CHCl3),
lography: 1H NMR (250 MHz, CD3OD, 296 K), δ (ppm)
3
porphyrin unit: 10.09 (s, 2H, methine), 7.81 (d, 2H, J H-H
)
)
)
3
3
7.2 Hz, phenyl), 7.71 (pseudo-t, 2H, J H-H ) 7.45 Hz, J H-H
3
3
7.6 Hz, phenyl), 7.60 (pseudo-t, 2H, J H-H ) 7.2 Hz, J H-H
λ
max (nm) 651, 622, 574, 543, 509, 435(s), 409; UV-vis (CHCl3
7.45 Hz, phenyl), 7.21 (d, 2H, 3J H-H ) 7.6 Hz, phenyl), 4.51 (s,
+ CH3OH), λmax (nm) 651, 623, 572, 541, 509, 408; FTIR (KBr,
cm-1) 3441, 2963, 2930, 2872, 1730, 1684, 1462, 1377, 1329,
1261, 1166, 1091, 1059, 1001, 971, 953, 943, 844, 754, 685;
HRMS-FAB (M+) calcd for C70H80N6O8 1132.60376, found
1132.60442.
4H, -CH2N<), 4.00 (q, 8H, 3J H-H ) 7.5 Hz, -CH2CH3), 2.46 (s,
3
12H, -CH3), 1.76(t, 12H, J H-H ) 7.5 Hz, -CH2CH3), Kemp’s
triacid unit: 2.16 (d, 4H, 2J H-H ) 14.0 Hz, cyclohexyl-H), 2.05
2
2
(d, 2H, J H-H ) 13.0 Hz, cyclohexyl-H), 1.38 (d, 2H, J H-H
)
2
13.0 Hz, cyclohexyl-H), 0.99 (d, 4H, J H-H ) 14.0 Hz, cyclo-
hexyl-H), 1.02 (s, 12H, -CH3), 0.76 (s, 6H, -CH3); UV-vis
(CH2Cl2), λmax (nm) 575, 543, 413.
r,â-5,15-Bis(r-N-(Kem p’s tr iacid im ido)-o-tolyl)-2,8,12,18-
tetr a eth yl-3,7,13,17-tetr a m eth ylp or p h yr in , H4(r,â-P DK).
Portions of H2(R,â-AP) (113 mg, 0.16 mmol), Kemp’s triacid
anhydride-chloride (85 mg, 0.32 mmol) and DMAP (4 mg, 0.032
mmol) were dissolved in anhydrous pyridine (10 mL). The
resulting solution was heated under argon at 95 °C for 16 h.
After the pyridine was removed by rotary evaporation, the
residue was dissolved in CHCl3 and washed three times
with brine. After the organic layer was dried over anhydrous
Na2SO4 and concentrated in a vacuum, the residue was
purified by flash column chromatography (silica gel, ethyl
acetate/methanol (v/v) ) 10/1) to afford H4(R,â-PDK) (167 mg,
90%): 1H NMR (250 MHz, CDCl3, 296 K), δ (ppm) porphyrin
unit: 10.16 (s, 2H, methine), 8.00-6.98 (m, 8H, phenyl), 4.23
(s, 4H, -CH2N<), 3.92 (q, 8H, 3J H-H ) 7.5 Hz, -CH2CH3), 2.49
X-r a y Cr ysta llogr a p h y. X-ray diffraction studies were
carried out using a Bruker (formerly Siemens) SMART CCD
X-ray instrument with a graphite-monochromatized Mo KR
radiation (λ ) 0.710 73 Å) controlled by a Pentium-based PC
running the SMART software package,51 as previously de-
scribed.52 Crystals were mounted at room temperature on the
ends of quartz fibers in Paratone N. Data collection was carried
out at -85 °C maintained by a Siemens LT-2A nitrogen
cryostat. Crystals were judged to be of acceptable quality on
the basis of initial unit cell matrixes and reflection profiles.
The raw data frames were integrated by the SAINT software
package53 on a Silicon Graphics Indy workstation. The refine-
ments were carried out with the SHELXTL software package.54
Hydrogen atoms were placed at calculated positions (C-H )
0.95-1.00 Å), with thermal parameters set equal to 1.2 times
(1.5 times for methyl groups) Beq of the atom to which they
were bound. They were included, but not refined, in the final
least-squares cycles. Crystallographic information is sum-
marized in Table S1 (Supporting Information).
3
(s, 12H, -CH3), 1.71 (t, 12H, J H-H ) 7.5 Hz, -CH2CH3),
Kemp’s triacid unit: 0.83 (br s, 12H, -CH3), 0.41 (br s, 12H,
-CH3), cyclohexyl proton was not identified due to the low
1
quality of the spectra, see H NMR of [ZnH2(R,â-PDK)]; UV-
vis (CH2Cl2), λmax (nm) 653, 626, 574, 542, 508, 408; HRMS-
FAB (M+) calcd for C70H80N6O8 1132.60376, found 1132.60329.
r,r-[5,15-Bis(r-N-(Kem p ’s
t r ia cid
im id o)-o-t olyl)-
Com p u ter Mod elin g. The molecular mechanics optimized
structure of H4(R,R-PDK) was obtained by CAChe program
using MM2 force field parameters. The energy terms included
in calculation are bond stretch, bond angle, dihedral angle,
improper torsion, van der Waals, electrostatics, and hydrogen
bond.
2,8,12,18-tetr a eth yl-3,7,13,17-tetr a m eth ylp or p h yr in ]zin c-
(II), [Zn H2(r,r-P DK)]. To a purple solution of H4(R,R-PDK)
(146 mg, 0.13 mmol) in CHCl3 (10 mL) was added a solution
of Zn(OAc)2‚2H2O (285 mg, 1.30 mmol) in CH3OH (5 mL). The
resulting pink purple solution was stirred at room temperature
for 13 h. After the solvents were removed, the residue was
treated with a small amount of CH2Cl2 and filtered through
Celite. The filtrate was concentrated and purified by flash
column chromatography (silica gel, ethyl acetate) to afford
[ZnH2(R,R-PDK)] as a pink purple solid (115 mg, 75%): UV-
vis (CH2Cl2), λmax (nm) 576, 544, 417; FTIR (KBr, cm-1) 3447,
2964, 2931, 2872, 1734, 1701, 1680, 1593, 1454, 1411, 1377,
1334, 1267, 1232, 1167, 1106, 1088, 1059, 1001, 872, 951, 878,
821, 758, 709, 669, 624, 598, 475; HRMS-FAB (M+) calcd for
Ack n ow led gm en t. This work was supported by
grants from the National Science Foundation, National
Institute of General Medical Sciences, and AKZO.
X.-X.Z. is grateful to the National Institutes of Health
for support under training grant CA09112 and for
postdoctoral fellowship GM18375.
Su p p or tin g In for m a tion Ava ila ble: X-ray crystallo-
graphic information including ORTEP and crystal packing
diagrams (Figures S1-S4). This material is available free of
charge via the Internet at http://pubs.acs.org.
C
70H78N6O8Zn 1194.51726, found 1194.51619.
r,â-[5,15-Bis(r-N-(Kem p ’s t r ia cid im id o)-o-t olyl)-
2,8,12,18-t e t r a e t h yl-3,7,13,17-t e t r a m e t h ylp or p h yr in ]-
zin c(II) [Zn H2(r,â-P DK)]. A saturated solution of zinc acetate
dihydrate (43 mg, 0.20 mmol) in methanol was added to a
solution of H4(R,â-PDK) (15 mg, 0.013 mmol) in CH2Cl2 (4 mL).
The resulting mixture was stirred in the dark at room
temperature. The reaction was monitored by TLC using CH2-
Cl2 as the developing solvent. After 6 h, the solvents were
removed and the residue was extracted with CHCl3 and
washed with water. After the organic layer was dried over
anhydrous Na2SO4, the solvent was evaporated to give a pink-
purple solid which was purified by flash column chromatog-
raphy (silica gel, ethyl acetate) to afford [ZnH2(R,â-PDK)]
J O000502V
(51) SMART. 4.0: Bruker Analytical X-ray System; Madison, WI.,
1994.
(52) Feig, A. L.; Bautista, M. T.; Lippard, S. J . Inorg. Chem. 1996,
35, 6892.
(53) SAINT 4.0: Bruker Analytical X-ray System; Madison, WI,
1995.
(54) SHELXTL: Struture Analysis Program 5.1; Bruker Analytical
X-ray System; Madison, WI, 1997.