De novo synthesis and photophysical characterization of annulated bacteriochlorins. Mimicking and extending the properties of bacteriochlorophylls

Article abstract of DOI:10.1039/c0nj00771d

Bacteriochlorophylls contain the bacteriochlorin chromophore and a fifth, five-membered oxopentano ring that encompasses positions 13-15 known as the "isocyclic" ring E. Such bacterio-13¹-oxophorbines have heretofore only been available in the

Full text of DOI:10.1039/c0nj00771d

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PAPER
De novo synthesis and photophysical characterization of annulated
bacteriochlorins. Mimicking and extending the properties of
bacteriochlorophyllsw
Michael Krayer,a Eunkyung Yang,b James R. Diers,c David F. Bocian,*c
Dewey Holten*b and Jonathan S. Lindsey*a
Received (in Montpellier, France) 8th October 2010, Accepted 22nd November 2010
DOI: 10.1039/c0nj00771d
Bacteriochlorophylls contain the bacteriochlorin chromophore and a fifth, five-membered
oxopentano ring that encompasses positions 13–15 known as the ‘‘isocyclic’’ ring E. Such
bacterio-131-oxophorbines have heretofore only been available in the naturally occurring
compounds, and analogues bearing six-membered rings have only been available by derivatization
of bacteriochlorophylls. A de novo route to synthetic bacteriochlorins, which bear a geminal
dimethyl group in each pyrroline ring, has been extended to gain access to a bacterio-131-
oxophorbine and bacteriochlorin-13,15-dicarboximides. The route relies on acid-catalyzed
condensation of a dihydrodipyrrin-acetal to form the bacteriochlorin, which then is subjected to
regioselective 15-bromination. Pd-mediated cyclization of the 15-bromobacteriochlorin bearing a
13-acetyl group (intramolecular a-arylation) or 13-ethoxycarbonyl group (carbamoylation and
intramolecular imidation) gives the bacterio-131-oxophorbine or bacteriochlorin-13,15-
dicarboximide, respectively. The resulting macrocycles exhibit absorption in the near-infrared
spectral region (733–818 nm), which extends the spectral coverage beyond that obtained
previously with synthetic bacteriochlorins that lack a fifth ring. The macrocycles also exhibit
excited singlet-state lifetimes (1.9–4.6 ns) comparable to or longer than those of natural
photosynthetic pigments. Density functional theory calculations predict that the bathochromically
shifted absorption is primarily due to lowering of the energy of the lowest unoccupied molecular
orbital. The new route complements existing semisynthetic routes and should enable fundamental
spectroscopic studies and diverse photochemical applications.
132-methoxycarbonyl substituent. Synthetic manipulation of
Introduction
bacteriochlorophylls has afforded a number of derivatives
Bacteriochlorins absorb strongly in the near-infrared spectral
region1 and hence are attractive candidates for a wide variety
132-methoxycarbonyl substituent, the phytyl-like chain, and
including (i) bacteriopyropheophorbides, which lack the
of photochemical studies, including artificial photosynthesis,2–9
the central magnesium;2–4,29,30 and (ii) bacteriopurpurinimides
photodynamic therapy (PDT),10–23 optical imaging,24–26
(hereafter referred to as bacteriochlorin-imides), which bear a
and perhaps flow cytometry.24,27 Naturally occurring
six-membered imide ring (Chart 1, panel B).6,12,16,17,31–37
bacteriochlorophylls a, b, and g contain the bacteriochlorin
The presence of the imide ring in bacteriochlorin-imides
chromophore and provide the basis for light-harvesting
provides a number of attractions including (1) a hyperchromic
processes and electron-transfer reactions in bacterial photo-
and bathochromic shift of the long-wavelength absorption
synthesis (Chart 1, panel A).28 Bacteriochlorophylls also
band; (2) the ability to introduce diverse groups at the nitrogen
of the imide ring;38 and (3) increased stability of the macrocycle
possess a five-membered ring (ring E) that encompasses the
13- and 15-positions; the ring contains a 131-oxo moiety and a
toward routine handling due to the presence of the second
carbonyl group at the 15-position. So far, bacteriochlorins
a Department of Chemistry, North Carolina State University, Raleigh,
North Carolina, 27695-8204, USA. E-mail: jlindsey@ncsu.edu
bearing the five membered oxopentano or six-membered imide
b Department of Chemistry, Washington University, St. Louis,
Missouri, 63130-4889, USA. E-mail: holten@wustl.edu
ring have only been available from the natural compounds or
upon semisynthesis therefrom, respectively, although synthetic
porphyrins and chlorins with a wide variety of annulated rings
have been prepared.39,40 Two significant problems in the
preparation of derivatives of bacteriochlorophylls include
c Department of Chemistry, University of California, Riverside,
California, 92521-0403, USA. E-mail: David.Bocian@ucr.edu
w Electronic supplementary information (ESI) available: Spectral data
for all new compounds. See DOI: 10.1039/c0nj00771d
c
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derivatization processes of the bacteriochlorins have been
examined (including regioselective bromination); however,
no annulated rings have yet been introduced.44–51 Here we
extend the de novo route to create stable, tailorable analogues
of the fundamental bacterio-131-oxophorbine and bacterio-
chlorin-13,15-dicarboximide macrocyclic skeletons (Chart 1,
panel C).52 The synthesis and spectroscopic analysis of such
synthetic macrocycles is essential for understanding the
structural features that underpin the characteristic spectral
properties of the naturally occurring bacteriochlorophylls.
Results and discussion
I
Retrosynthetic analysis
An approach to stable bacterio-131-oxophorbine and
bacteriochlorin-13,15-dicarboximide macrocycles is outlined in
Scheme 1. The bacteriochlorin macrocycle is created upon
acid-catalyzed condensation of
a dihydrodipyrrin-acetal.
Subsequent derivatization to install the annulated rings builds
Chart 1 (A) Naturally occurring bacteriochlorophylls. (B) Derivatives
of naturally occurring bacteriochlorophylls. (C) Nomenclature of the
core macrocycles.
limited stability36,41,42 and poor synthetic malleability owing
to the presence of a nearly full complement of substituents
about the perimeter of the macrocycle.13,18 The synthesis of
bacteriochlorins by reduction or addition of porphyrins or
chlorins is appropriate for a number of applications but
generally suffers from a lack of regiocontrol.43
Over the past decade we have been developing a de novo
synthesis of bacteriochlorins.44–46 The route affords bacterio-
chlorins wherein each pyrroline ring contains a geminal
dimethyl group rather than the trans-dialkyl and exo-ethylidene
moieties of the naturally occurring bacteriochlorophylls. The
geminal dimethyl group has the attractive feature of stabilizing
the macrocycle toward adventitious dehydrogenation. Synthetic
bacteriochlorins bearing diverse substituents at specific
sites in the pyrrolic units have been prepared, and selected
Scheme 1 Retrosynthetic analysis of stable synthetic bacteriochlorins
containing a fifth ring.
c
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on the strategies we have developed in chlorin chemistry for
the preparation of the 131-oxophorbine53 and chlorin-imide54
frameworks. Thus, the construction of both rings relies on
regioselective 15-bromination followed by intramolecular
Pd-mediated ring closure. Access to the former requires the
presence of a 13-acetyl group for a-arylation55 whereas
the latter requires a 13-ester group for carbonylation and
imidation.
II Regioselective 15-bromination
A number of 5-methoxy substituted bacteriochlorins are
known to undergo regioselective 15-bromination.46,47 Therefore,
an initial approach to the target bacteriochlorin-131-oxophorbine
was to convert the 3,13-dibromo-5-methoxybacteriochlorin
MeOBC-Br to the 3,13-diacetyl-5-methoxybacteriochlorin
MeOBC-A followed by 15-bromination and Pd-mediated ring
closure. However, the presence of 3,13-diacetyl groups in
MeOBC-A caused loss of regioselectivity during the bromination
step (Scheme 2). This result was not entirely surprising, given
that the same loss of regioselectivity was observed in the case
of a bacteriochlorin bearing 3,13-diester groups.46 MeOBC-A
was treated with ethylene glycol and TMSCl56 to form the
ketal-protected analogue MeOBC-K in an attempt to mitigate
the electron-withdrawing effect of the acetyl group, but again
regioselective bromination was not obtained (Scheme 2).
To effect regioselective 15-bromination in the presence of
electron-withdrawing substituents (e.g., acetyl or ester), the
remaining b-pyrrolic positions need to be blocked, which can
be achieved with alkyl groups. Indeed, we have previously
reported the regioselective bromination of 2,12-diethyl-3,13-
diethoxycarbonyl-5-methoxybacteriochlorin MeOBC-EtEs to
give the key precursor to the bacteriochlorin-13,15-dicarbox-
imides, the 15-bromobacteriochlorin MeOBC-EtEs-Br15
(Scheme 3).46 The use of bacteriochlorins wherein the three
b-pyrrolic sites that are not integral to ring E are substituted
(i.e., positions 2, 3, and 12) proved to be an essential requirement
for the approaches developed here to introduce the two ring E
motifs.
Scheme
2
Attempted synthesis of
a
15-bromo-3,13-diacetyl-
bacteriochlorin.
III Synthesis
The target bacterio-131-oxophorbine was pursued via the
intermediacy of dihydrodipyrrin-acetal 1, which bears bromo
and methyl substituents at the b-pyrrolic positions (Scheme 4).
Upon conversion to the bacteriochlorin, the bromo substituent
provides a synthetic handle for introduction of the acetyl
group, and the methyl group prevents bromination at the
pyrrolic positions during 15-bromination. Preparation of 1
closely follows the optimized condition for a dihydrodipyrrin-
acetal lacking the methyl group on the pyrrole.50 The synthesis
of 1 entails formation of 3-methyl-pyrrole-2-carboxaldehyde
(2) by photochemical rearrangement of 4-picoline-N-oxide,57
bromination to give bromopyrrole 3, tosyl-protection of the
pyrrole (3-Ts), nitro-aldol (Henry) condensation followed by
reduction to give the 2-(2-nitroethyl)pyrrole 4-Ts, Michael
addition with the a,b-unsaturated ketone-acetal 544 to give
the nitrohexanone-pyrrole 6-Ts, removal of the tosyl group
(6-H), and McMurry-type ring closure to 1. The presence of
Scheme 3 Prior demonstration of regioselective 15-bromination.
the tosyl group was necessary to increase the stability of key
intermediates.
Dihydrodipyrrin-acetal 1 was subjected to self-condensation
conditions optimized for selective formation of either the
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23 h45 instead of DMF/CH3CN59 for 2 h; the latter afforded
mono-reacted bromo-acetylbacteriochlorin.) 15-Bromination of
5-methoxybacteriochlorin MeOBC-MeA proceeded smoothly to
give MeOBC-MeA-Br15, whereas treatment of 5-unsubstituted-
bacteriochlorin HBC-MeA with 1 equiv. of NBS gave the 5,15-
dibromobacteriochlorin BC-MeA-Br5,15 as the major product.
Nonetheless, Pd-mediated intramolecular a-arylation of
MeOBC-MeA-Br15 created ring E and thereby completed the
synthesis of the 5-methoxybacterio-131-oxophorbine MeOBOP
(Scheme 5). Attempted double cyclization of BC-MeA-Br5,15
to give the bacteriochlorin-31,131-dioxophorbine was
unsuccessful.
For the synthesis of bacteriochlorin-13,15-dicarboximides,
the known diester-bacteriochlorins46 MeOBC-EtEs and
HBC-EtEs were subjected to bromination. As before
(Scheme 3), the bromination of 5-methoxybacteriochlorin
MeOBC-EtEs proceeded smoothly to give the 15-bromo-
bacteriochlorin MeOBC-EtEs-Br15.46 On the other hand,
HBC-EtEs gave predominantly the 5,15-dibrominated product;
however, the mono-brominated HBC-EtEs-Br15 was isolated
in sufficient quantities to complete the synthesis. Treatment of
MeOBC-EtEs-Br15 or HBC-EtEs-Br15 in the presence of
benzylamine to one-flask Pd-mediated carbamoylation and
ring closure resulted in the bacteriochlorin-13,15-dicarboximide
MeOBC-I or HBC-I, respectively (Scheme 6).
IV Structural characterization
The bacteriochlorins were characterized by 1H NMR spectro-
scopy, IR spectroscopy, high resolution mass spectrometry
(ESI-MS), absorption spectroscopy and fluorescence spectro-
scopy. We first consider the 1H NMR data. In general, a
bacteriochlorin that has C2h symmetry (such as the H-BC-type
macrocycles lacking the fifth ring or the 15-bromo substituent)
1
exhibits a relatively simple H NMR spectrum. Introduction
of a single substituent (e.g., 5-methoxy, 15-bromo or ring E)
results in Cs symmetry whereupon a number of otherwise
identical structural elements in the respective A,C and B,D
rings become magnetically non-equivalent and split into
distinct signals. The non-equivalent entities include the two
pyrrolic N–H protons, the pair of geminal dimethyl groups,
the CH2 group in each of the two pyrroline rings, and any
b-pyrrolic substituents (e.g., methyl unit of the acetyl group in
MeOBC-MeA). The synthetic bacteriochlorins synthesized to
date typically exhibit a broad upfield peak in the region
d À2.40–0.12 ppm (pyrrolic N–H protons), a singlet between
d 1.81–2.02 ppm (geminal dimethyl groups), and a singlet
between d 4.30–4.50 ppm (pyrroline CH2 groups). The
1H NMR signal for the 5-methoxy group generally resonates
in the region d 3.68–4.48 ppm.44–46
Scheme 4 Synthesis of a bromo-dihydrodipyrrin-acetal.
The 1H NMR spectrum of bacterio-131-oxophorbine
MeOBOP displays the aforementioned features characteristic
of bacteriochlorins with Cs symmetry. In addition, the two
protons at the 132-position (ring E) resonate as a singlet at
d 4.88 ppm, to be compared with the ABX pattern of the
diastereotopic 132-protons of bacteriopyro-131-oxophorbines
(owing to the presence of stereocenters at positions 17 and
18 in the neighboring ring).3,29,36,60 The chemical shift range
is comparable to those of bacteriochlorophyll a derivatives
5-methoxybacteriochlorin or the 5-unsubstituted-bacterio-
chlorin.44,46 Thus, self-condensation of 1 in CH2Cl2 containing
TMSOTf/2,6-DTBP gave MeOBC-MeBr; self-condensation in
CH3CN containing BF3ÁOEt2 gave HBC-MeBr. Stille coupling of
each bacteriochlorin with tributyl(1-ethoxyvinyl)tin58 followed
by acidic hydrolysis gave diacetylbacteriochlorins MeOBC-MeA
and HBC-MeA. (Note: the reactions were carried out in THF for
c
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Scheme 6 Synthesis of a bacteriochlorin-13,15-dicarboximide.
chemistry, the 13-ester-15-bromochlorin gave exclusively the
chlorine-imide, whereas imide and isoimide mixtures were
sometimes observed upon reaction of the 13-carbamoyl-15-
bromochlorin.54 A convenient method for distinguishing the
two isomers relied on the chemical shift of the methylene
protons of the N-benzyl (iso)imide: d 5.6 ppm for the
chlorin-imides versus 5.2 ppm for the corresponding chlorin-
isoimides.54 In the work reported herein, MeOBC-I and
HBC-I were each obtained from the corresponding 13-ester-
15-bromobacteriochlorin, and the benzylic protons of
MeOBC-I and HBC-I resonated at d 5.67 and 5.68 ppm,
respectively. Such data by analogy with the chlorins are
consistent with the formation of bacteriochlorin-imides.
The IR spectrum of MeOBOP shows carbonyl stretching
bands at 1687 and 1630 cmÀ1
, along with bands at
2918–2954 cmÀ1 (C–H) and 3435 cmÀ1 (N–H). In comparison,
Scheme 5 Synthesis of a bacterio-131-oxophorbine.
the carbonyl stretch of a bacteriochlorin in a dyad (bacterio-
(d 4.76–5.31 ppm) and synthetic chlorophyll analogues
(131-oxophorbines, d 5.03–5.16 ppm).53,59
The bacteriochlorin-13,15-dicarboximides MeOBC-I and
pyropheophorbide–pyromellitimide) occurs at 1695 cmÀ1 3
whereas that of a zinc chelate of a bacterio-131-oxophorbine
appears at 1682 cmÀ1 61
The carbonyl stretch for a variety of
methyl pyropheophorbides (chlorins) occurs in the region
1650–1699 cmÀ1 62,63
Kunieda and Tamiaki have used IR
,
1
.
HBC-I also display H NMR spectral features characteristic
1
of bacteriochlorins with Cs symmetry. The H NMR spectra
.
of MeOBC-I and HBC-I also provide information on
the formation of the imide and/or isoimide ring, which are
ever-present possibilities in the imidation process. In chlorin
extensively to identify hydrogen-bonding with hydroporphyrin
carbonyl groups in supramolecular assemblies.61,63 The IR
c
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spectra of MeOBC-I and HBC-I show carbonyl stretching bands
in the range of 1647–1682 cmÀ1, along with bands in the
region 2848–2959 cmÀ1 (C–H) and 3386–3435 cmÀ1 (N–H).
To our knowledge, IR data have not been reported for other
bacteriochlorin-imides.
V Absorption spectra
The annulated bacteriochlorins prepared herein exhibit
characteristic bacteriochlorin absorption spectra,1 with near-
ultraviolet (Soret or B) bands, a long-wavelength feature, the
Qy(0,0) band, in the near-infrared region of comparable peak
intensity, and the weaker Qx bands in the intervening region
(500–600 nm). The position of the long wavelength absorption
band of a photochemically active species is of central importance,
defining not only the spectral region where absorption occurs but
also the energy of the lowest singlet excited-state, which
dominates key photophysical properties. These properties
include fluorescence and, for the native bacteriochlorophylls,
the energy- and electron-transfer reactions of photosynthesis.
Prior studies with synthetic bacteriochlorins have shown
that the position of the Qy(0,0) band could be tuned
from 707 nm to 792 nm (typically measured in toluene).51,44–46
The synthetic bacterio-131-oxophorbine MeOBOP (733 nm)
absorbs in this range, to be compared with that of methyl
Fig. 1 Absorption (— solid lines) and emission (- - - dashed lines)
spectra (normalized) in toluene at room temperature of MeOBOP
(blue), MeOBC-I (green), and HBC-I (magenta).
diminished in bacteriochlorins that lack a carbonyl moiety
(acetyl, ester, imide) at the 3,13-positions. This point is seen
upon comparison of the Qy(0,0) positions of bacteriochlorins
MeOBC (709 nm)46 and HBC (713 nm)45 that bear one or no
substituents, respectively, other than the geminal dimethyl
groups (Chart 2).
bacteriopyropheophorbide
a
(754 nm in CH2Cl2).29
VI Fluorescence spectra, quantum yields, and singlet excited-
state lifetimes
Bacteriopheophytin a (BPh-a), which differs from methyl
bacteriopyropheophorbide a owing to the presence of a
132-methoxycarbonyl group and a long alkyl ester chain, also
absorbs at 750–760 nm in hydrocarbon solvents.64,65 The
bacteriochlorin-imides MeOBC-I (793 nm) and HBC-I (818
nm) exhibit Qy(0,0) bands that extend further into the near
infrared. The Qy(0,0) band of bacteriochlorin-imides derived
from bacteriochlorophyll a occurs in the same spectral range
(800–830 nm).32,33,36
The fluorescence spectra of MeOBOP, MeOBC-I and HBC-I
in toluene are shown in Fig. 1 (dotted lines). Each fluorescence
spectrum is dominated by the Qy(0,0) band, which lies B5 nm
to longer wavelength than the corresponding Qy(0,0)
absorption feature. The same is generally true for the
benchmark bacteriochlorins listed in Table 1; exceptions
include HBC-EtEs and MeOBC-EtEs, which show larger
(10–15 nm) Stokes shifts, suggesting greater changes in structure
or solvent interactions upon photoexcitation.
The spectra of MeOBOP, MeOBC-I and HBC-I in toluene
are shown in Fig. 1. The Qy(0,0) positions are listed in Table 1
along with those of a number of bacteriochlorin benchmarks
that lack the annulated ring E. Reference molecules for
MeOBOP include a set of 3,13-diacetylbacteriochlorins:
MeOBC-MeA (743 nm), MeOBC-A (740 nm), HBC-MeA
(766 nm) and HBC-A (768 nm). The first three of these 3,13-
diacetylbacteriochlorins were prepared here (Schemes 2 and 5)
whereas HBC-A (Chart 2) was synthesized previously.45
Comparison among the four 3,13-diacetylbacteriochlorins
shows that (1) the 5-methoxy group results in an average
25 nm hypsochromic shift in the Qy(0,0) position, and (2)
the 2,12-dimethyl groups have little (p3 nm) effect on the
Qy(0,0) position. The first point, regarding the 5-methoxy
group, is also made upon comparison of the Qy(0,0)
positions of bacteriochlorins MeOBC-EtEs (739 nm) and
HBC-EtEs (761 nm).46 The latter two compounds (Scheme 6)
serve as benchmarks for the two bacteriochlorin-imides
(MeOBC-I and HBC-I): the benchmarks contain the 2,12-
diethyl and 3-ester groups but lack the 13,15-dicarboximide
moiety. The Qy(0,0) position for MeOBC-I (793 nm) and
HBC-I (818 nm), like the three pairs of bacteriochlorins noted
above, shows a 25 nm hypsochromic shift due to the 5-methoxy
group. Interestingly, the impact of the 5-methoxy group is
The bathochromic shift of the Qy(0,0) band of MeOBOP,
MeOBC-I and HBC-I (733 nm, 793 nm, 818 nm) is accompanied
by a decrease in the fluorescence yield (0.19, 0.052, 0.036) and
shortening of the singlet excited-state lifetime (4.6 ns, 2.2 ns,
1.9 ns). The same is true of the benchmark bacteriochlorins.
These data are plotted in Fig. 2C and D and listed in Table 1.
For comparison, the singlet excited-state lifetime of bacterio-
pheophytin a is 2.0–2.7 ns and has a Qy(0,0) band at
750–760 nm in organic solvents (Table 1).64,65 Thus, the two
synthetic bacteriochlorin-imides absorb at significantly longer
wavelengths (by B40 and B70 nm) than the natural pigment
and yet have comparable excited-state lifetime.
VII Frontier molecular orbitals and electronic properties
The energies and electron-density distributions of the frontier
molecular orbitals (MOs) of the bacterio-131-oxophorbine,
bacteriochlorin-imides, and benchmark compounds were
obtained from density functional theory (DFT) calculations.
Such methods were also applied to the fictive bacteriochlorin
MeOBC-MeAMe15 (Chart 3), which differs from the benchmark
compound MeOBC-MeA in the addition of a 15-methyl
substituent. Examination of MeOBC-MeAMe15 provides
c
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Table 1 Photophysical properties of bacteriochlorin compoundsa
tsd/ns HOMO À LUMOe/eV HOMO-1 À LUMO+1f/eV
b
Compound
Cmpd code for Fig. 2 lQ abs/nm lQ em/nm IQ /IB Ffc
y
y
y
Targets:
HBC-I
MeOBC-I
MeOBOP
Benchmarks:
HBC
a
b
h
818
793
733
823
798
739
1.3
1.0
0.93
0.036 1.9
0.052 2.2
0.19 4.6
1.92
2.02
2.18
4.01
3.92
3.86
i
c
713
768
766
761
709
740
743
739
758
716
771
0.85
1.2
0.17 4.0
0.11 2.9
2.26
2.05
2.02
2.10
2.28
2.14
2.14
2.16
2.03h
4.06
3.95
3.94
3.98
3.98
3.88
3.87
3.91
3.89h
HBC-A
HBC-MeA
HBC-EtEs
MeOBC
MeOBC-A
MeOBC-MeA
MeOBC-EtEs
BPh-ag
d
j
f
e
g
775
711
747
749
749
768
0.94
0.87
0.96
0.95
1.1
0.14 3.3
0.25 5.0
0.14 3.8
0.13 3.4
0.17 4.3
0.10 2.7
0.69
Fictive:
MeOBC-MeAMe15
2.17
3.80
a
b
In toluene at room temperature unless noted otherwise. Ratio of the peak intensities of the Qy(0,0) and B bands. Fluorescence quantum yield
c
d
(error Æ 7%). Lifetime of the lowest singlet excited state measured using fluorescence techniques (error Æ 7%). Values for several of the
e
benchmark compounds were reported in ref. 45. Energy gap between the LUMO and HOMO orbitals. Energy gap between the LUMO+1 and
f
g
HOMO-1 orbitals. Values in toluene. The values in ethanol are labs = 750 nm, lem = 768 nm, IQ /IB = 0.39, Ff = 0.081, and ts = 2.3 ns.
A value of ts = 2.0 ns in acetone/methanol 7 : 3 was found in ref. 65. DFT calculations were performed with the truncated phytyl tail
y
h
–CH2CHQC(CH3)(CH2CH3).
wavelength/energy of the Qy(0,0) absorption band than are the
HOMO (m = 1.8), LUMO+1 (m = 2.3) and HOMO-1
(m = 2.4). These differences can be traced to the generally
greater electron density in the LUMO at the substituent sites
(Table 2). The most important sites in this regard are the
3,13-positions of the carbonyl substituents (acetyl, ester,
imide) of MeOBOP, MeOBC-I, HBC-I and the benchmark
bacteriochlorins. These sites (and the 2,12-positions) are on
the molecular y-axis, which is the axis on which the Qy optical
transition is polarized.
(2) In Gouterman’s four-orbital model,66,67 the position of
the Qy(0,0) absorption band depends on the average value of
the HOMO À LUMO energy gap and the HOMO-1 À
LUMO+1 energy gap. Because of the trends in the individual
molecular orbitals described above and shown in Fig. 2A,
there is a much greater variation in the HOMO À LUMO
energy gap versus the HOMO-1 À LUMO+1 energy gap
for MeOBOP, MeOBC-I, HBC-I and the benchmark
bacteriochlorins (Table 1). The consequence is a much
greater magnitude of the slope of the trend line for the
Chart 2 Benchmark bacteriochlorins prepared previously.45
deeper insight into the origin of the effects caused by the
formation of the fifth ring. The four frontier molecular orbitals
and energy levels for nine compounds are shown in Table 2.
The key results of the DFT calculations for MeOBOP,
MeOBC-I, HBC-I and representative benchmark synthetic
and fictive compounds are summarized in Fig. 2. This figure
shows the characteristics of the four frontier orbitals: the
highest occupied molecular orbital (HOMO), the lowest
unoccupied molecular orbital (LUMO), the HOMO-1, and
LUMO+1. The energies of these MOs are plotted as a
function of the Qy(0,0) absorption-band energy/wavelength
in Fig. 2A, and analogous plots for the HOMO À LUMO
energy gap and HOMO-1 À LUMO+1 energy gap are shown
in Fig. 2B. In each of these plots, the data for the key target
compounds (MeOBOP, MeOBC-I and HBC-I) are given by
closed symbols and those for the benchmark bacteriochlorins
by open symbols. The values for the HOMO À LUMO and
HOMO
À
LUMO energy gap (m = 1.4) versus the
HOMO-1 À LUMO+1 energy gap (m = À0.05) plotted
against the Qy(0,0) wavelength/energy (Fig. 2B). Consequently,
the wavelength/position of the Qy(0,0) band is dominated by
the HOMO À LUMO energy gap for the bacterio-131-
oxophorbine, bacteriochlorin-imides, and bacteriochlorins
described here. In turn, following the findings given in point
(1), the spectral position is dictated much more strongly by
the dependence of the LUMO than the HOMO on the
macrocycle-substituent pattern for these molecules.
HOMO-1
À
LUMO+1 energy gaps for the various
compounds are listed in Table 1. These two energy gaps are
relevant to the spectral analysis given below.
(3) The DFT calculations reproduce the effect of the
5-methoxy group on the position of the Qy(0,0) wavelength/
energy. This can be seen by comparing the value for the
Qy(0,0) wavelength and the HOMO À LUMO energy
gap for the following pairs of 3,13-dicarbonyl-containing
(acetyl, ester, imide) compounds (Table 1): MeOBC-I
The salient points from the DFT calculations and the
relationship to the observed spectral properties are as follows:
(1) The slopes of the trend lines given in Fig. 2A show that
the LUMO (m = 3.2) is more strongly connected with the
c
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Chart 3 Fictive bacteriochlorin for which DFT calculations were
performed.
reveal a much smaller spectral shift of 4 nm and a correspond-
ing smaller molecular-orbital energy-gap shift of 0.02 eV.
Obviously there is interplay between the electron-donating
ability of the 5-methoxy group and the sensitivity of the
3,13-positions to the presence of auxochromes such as carbonyl
moieties.
(4) The DFT calculations of the benchmark compounds
reproduce the finding that the 2,12-dimethyl groups of bacterio-
131-oxophorbine MeOBOP, and in analogy the 2-ethyl group
of MeOBC-I and HBC-I, have little effect. This result is shown
by the Qy(0,0) wavelength and the HOMO À LUMO energy
gap for the following pairs of compounds: HBC-A (768 nm,
2.05 eV) versus HBC-MeA (766 nm, 2.02 eV); and MeOBC-A
(740 nm, 2.14 eV) versus MeOBC-MeA (743 nm, 2.14 eV). In
both cases the presence of the 2,12-dimethyl groups results in
r3 nm spectral shift and a r0.03 eV shift in the molecular-
orbital energy gap. Collectively, these results suggest that the
alkyl groups at the 2- or 12-positions of MeOBOP, MeOBC-I
and HBC-I, and by implication the native photosynthetic
pigments, such as BPh-a (Table 2), play an insignificant role
in determining the spectral properties of these molecules.
(5) The data and analysis given above (Table 1 and Fig. 1
and 2) provide insights into which substituents are most
responsible for the spectral characteristics of MeOBOP versus
that of the benchmark bacteriochlorin MeOBC. The Qy(0,0)
position and HOMO À LUMO gap for MeOBC (709 nm,
2.28 eV) are strongly affected upon the addition of the 3,13-
diacetyl groups (MeOBC-A: 740 nm, 2.14 eV), with little
further effect upon addition of the 2,12-dimethyl groups
(MeOBC-MeA: 743 nm, 2.14 eV). The final step to obtain
MeOBOP (733 nm, 2.18 eV) is closure to form the five-
membered ring. The latter can be thought of as first, placement
of a substituent at the 15-methyl group, and second, ring
closure accompanied by structural/electronic effects such as
ring strain and shift toward planarity. To gain insights into the
effect of the 15-substituent, DFT calculations were carried out
on the fictive bacteriochlorin MeOBC-MeAMe15, wherein a
methyl group is placed at the 15-position (Chart 3, Tables 1
and 2). The HOMO À LUMO energy gap (2.17 eV) for this
fictive compound is between those for MeOBC-MeA
(2.14 eV) and MeOBOP (2.18 eV), consistent with a modest
effect of substitution at the 15-position. Given the small
(0.03–0.04 eV) energy shifts involved, however, the effects of
15-substitution versus ring closure (once the 13-acetyl group is
in place) are of uncertain relative magnitude in dictating the
ultimate spectral properties of the bacterio-131-oxophorbine
chromophores.
Fig. 2 Orbital energies, energy gaps, singlet excited-state lifetime, and
fluorescence yield as a function of the Qy(0,0) energy (bottom axis) and
wavelength (top axis). For each plot, the solid symbols are for the
three target compounds, MeOBOP, MeOBC-I and HBC-I, and the
open symbols are for the benchmark bacteriochlorins. The letter code
(a–j) at the bottom of panel A gives the left-to-right order of the data
points for each plot in the figure and identifies the compounds as listed
in the first two columns of Table 1.
(793 nm, 2.02 eV) versus HBC-I (818 nm, 1.92 eV); MeOBC-
EtEs (739 nm, 2.16 eV) versus HBC-EtEs (761 nm, 2.10 eV);
MeOBC-MeA (743 nm, 2.14 eV) versus HBC-MeA (766 nm,
2.02 eV); and MeOBC-A (740 nm, 2.14 eV) versus HBC-A
(768 nm, 2.05 eV). For these pairs of compounds (with versus
without the 5-methoxy group), the average bathochromic shift
is 24 nm and the average shift in the HOMO À LUMO gap to
lower energy is 0.09 eV. By comparison, the values for
MeOBC (709 nm, 2.28 eV) versus HBC (713 nm, 2.26 eV)
c
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c
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acetonitrile/DMF [20 mL (3 : 2)] at 85 1C for 1.5 h. The
reaction mixture was treated with 10% aqueous HCl
(50 mL) at room temperature for 20 min and then diluted
with CH2Cl2. The reaction mixture was poured into a saturated
aqueous solution of NaHCO3 and extracted with dichloro-
methane. The organic layer was dried (Na2SO4), concentrated
and chromatographed (silica, CH2Cl2) to afford a purple solid
(64 mg, 68%): 1H NMR d À1.68 (br s, 1H), À1.31 (br s, 1H),
1.90 (s, 6H), 1.95 (s, 6H), 3.08 (s, 3H), 3.16 (s, 3H), 4.18 (s,
3H), 4.36 (s, 2H), 4.39 (s, 2H), 8.54 (s, 1H), 8.63 (s, 1H), 8.66
(d, J = 2.2 Hz, 1H), 9.08 (d, J = 1.93 Hz, 1H), 9.77 (s, 1H);
13C NMR d 29.9, 31.0, 31.3, 33.2, 45.5, 46.1, 48.2, 51.6, 64.9,
97.6, 99.6, 99.8, 121.3, 125.7, 128.3, 129.1, 133.0, 135.1, 135.6,
135.7, 135.9, 157.2, 162.5, 169.2, 172.8, 197.0, 202.5; ESI-MS
obsd 485.25401; calcd 485.25527 [(M + H)+, M = C29H32N4O3];
labs (CH2Cl2) 362, 530, 742 nm.
Outlook
Bacteriochlorophylls are Nature’s pigments for absorption of
sunlight in the near-infrared region. The ability to utilize such
compounds in diverse artificial systems—such as artificial
photosynthesis, clinical diagnostics, and photomedicine—
depends on versatile synthetic methods that afford stable
macrocycles and that enable the spectral properties to be
tuned at will. The designs we have chosen employ a geminal
dimethyl group in each pyrroline ring to ensure stability
toward adventitious dehydrogenation. The resulting synthetic
bacteriochlorins thus differ slightly in structure from the
natural pigments, yet are more robust toward routine handling
and synthetic manipulation. Here we have explored the ability
to install an exocyclic ring, either the five-membered isocyclic
ring as occurs in all bacteriochlorophylls, or the six-membered
imide ring characteristic of derivatives of bacteriochlorophylls
commonly known as bacteriopurpurinimides.
3,13-Bis(2-methyl-1,3-dioxolan-2-yl)-5-methoxy-8,8,18,18-
tetramethylbacteriochlorin (MeOBC-K). Following a known
procedure,56 a solution of MeOBC-A (20.0 mg, 0.0413 mmol)
in CH2Cl2 (3.5 mL) was treated with ethylene glycol (470 mL,
82.6 mmol) and TMSCl (422 mL, 3.30 mmol). The mixture was
stirred at room temperature for 6 h. A saturated aqueous
solution of NaHCO3 was added and the mixture was extracted
with CH2Cl2. The organic layer was separated, dried (Na2SO4)
and concentrated under vacuum. Column chromatography
(alumina, CH2Cl2) afforded a green solid (17 mg, 72%):
1H NMR d À2.06 (br s, 1H), À1.86 (br s, 1H), 1.945 (s, 6H),
1.951 (s, 6H), 2.33 (s, 3H), 2.40 (s, 3H), 4.12–4.33 (m, 4H), 4.25
(s, 3H), 4.34–4.50 (m, 4H), 4.42 (s, 2H), 4.44 (s, 2H), 8.576 (s,
1H), 8.584 (s, 1H), 8.73 (d, J = 2.75 Hz, 1H), 8.79 (d, J =
2.75 Hz, 1H), 9.08 (s, 1H); LD-MS obsd 572.7, calcd 572.3
(C33H40N4O5); labs (CH2Cl2) 356, 367, 505, 715 nm.
Of the de novo synthesized bacteriochlorins that we have
prepared to date, MeOBC46 and HBC45 are at the shorter
wavelength end of the range of Qy(0,0) absorption positions
while the two bacteriochlorin-imides MeOBC-I and HBC-I
are at the longer extreme. A naturally occurring bacteriochlorin
(wherein each pyrroline ring bears a geminal dialkyl unit and
an oxo group) known as tolyporphin A absorbs at 678 nm.68
The ability to tune the absorption band almost at will from
B680–820 nm bodes well for the use of synthetic bacterio-
chlorins, bacterio-131-oxophorbines, and bacteriochlorin-
13,15-dicarboximides in diverse photochemical applications.
The pursuit of such applications will be facilitated by the
fluorescence yields (0.036–0.19), singlet excited-state lifetimes
(1.9–4.6 ns), and photostability of the bacterio-131-oxophorbine
and bacteriochlorin-13,15-dicarboximides prepared herein, as
well as the obvious sites for synthetic elaboration provided by
the keto and N-imide groups of the annulated ring E.
8-Bromo-2,3-dihydro-1-(1,1-dimethoxymethyl)-3,3,7-trimethyl-
dipyrrin (1). Following a procedure for the synthesis of bromo-
dihydrodipyrrin-acetals,50 in a first flask a solution of 6-H
(4.77 g, 12.2 mmol) in freshly distilled THF (30 mL) at 0 1C
was treated with freshly prepared NaOMe (3.3 g, 61 mmol).
The resulting mixture was stirred and degassed by bubbling
argon through the solution for 45 min. In a second flask
purged with argon, TiCl3 (46 mL, 20% in 3% HCl solution,
73 mmol), THF (90 mL), NH4OAc (35 g, 0.46 mol), and
degassed water (50 mL) were combined under argon and the
solution was degassed by bubbling argon through the solution
for 45 min. Then the first flask mixture was transferred via
cannula to the buffered TiCl3 solution. The resulting mixture
was stirred at room temperature for 16 h under argon. A
saturated solution of aqueous NaHCO3 (300 mL) was added
followed by ethyl acetate (200 mL). The mixture was extracted
with ethyl acetate. The organic layer was dried (Na2SO4),
concentrated to a brown oil, dried under high vacuum for 2 h,
and chromatographed on a short alumina column (neutral
alumina, CH2Cl2) to give a light brown oil (1.40 g, 34%):
1H NMR d 1.22 (s, 6H), 2.10 (s, 3H), 2.62 (s, 2H), 3.44 (s, 6H),
5.01 (s, 1H), 5.80 (s, 1H), 6.73–6.84 (m, 1H), 10.66 (br s, 1H);
13C NMR d 10.1, 29.4, 40.5, 48.4, 54.8, 99.6, 102.9, 105.1,
117.3, 117.9, 127.5, 159.9, 174.7; ESI-MS obsd 341.0865, calcd
341.0859 [(M + H)+, M = C15H21BrN2O2].
Experimental section
I
General methods
1H NMR spectra (300 MHz) and 13C NMR spectra
(100 MHz) were collected at room temperature in CDCl3.
Silica gel (40 mm average particle size) was used for column
chromatography. All solvents were reagent grade and were
used as received unless noted otherwise. THF was freshly
distilled from sodium/benzophenone ketyl. Laser-desorption
mass spectrometry was performed without any matrix.
Electrospray ionization mass spectrometry (ESI-MS) data
are reported for the molecule ion or protonated molecule
ion. Known compounds 3-methyl-pyrrole-2-carboxaldehyde
(2),57 1,1-dimethoxy-4-methyl-3-penten-2-one (5),44 and
two bacteriochlorins (HBC-EtEs, MeOBC-EtEs-Br15)46 were
prepared according to literature procedures.
3,13-Diacetyl-5-methoxy-8,8,18,18-tetramethylbacteriochlorin
(MeOBC-A). Following a procedure for replacement of a
bromo group with an acetyl group on a bacteriochlorin
with modification,46,58 a mixture of MeOBC-Br (108 mg,
0.194 mmol), tributyl(1-ethoxyvinyl)tin (135 mL, 0.388 mmol),
and (PPh3)2PdCl2 (56 mg, 0.078 mmol) was heated in
c
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4-Bromo-3-methylpyrrole-2-carboxaldehyde (3). Following a
general procedure,50 a stirred solution of 3-methyl-pyrrole-2-
carboxaldehyde (2, 5.63 g, 51.6 mmol) in THF (52 mL) was
cooled to 0 1C. NBS (9.19 g, 51.6 mmol; reagent grade,
unrecrystallized) was added all at once. The reaction mixture
was stirred for 15 min at 0 1C under argon before the solvent
was removed on a rotary evaporator. The resulting solid was
dried under high vacuum for 2 h. Water (100 mL, room
temperature) was added to the flask and the suspension was
was washed with water (200 mL) followed by cold ethanol
(B100 mL, 0 1C) until the eluant was clear. The yellow filtered
solid was dried overnight under high vacuum. The crude solid
material was dissolved in dry THF (117 mL, distilled). The
solution was cooled to À10 1C (internal temperature, using an
acetone bath with a few pieces of dry ice) under argon. The
solution was treated with 95% LiBH4 (0.64 g, 28 mmol) all at
once under vigorous stirring. The reaction mixture was stirred
for B15 min at À10 1C, until all of the starting material
disappeared (starting material: CHQCHNO2: d, J = 13.6 Hz,
8.56 ppm; product: CH2CH2NO2: t, J = 7.3 Hz, 4.54 ppm and
3.36 ppm), whereupon the reaction mixture was quenched by
slowly adding a cold saturated aqueous NH4Cl solution
(200 mL, 0 1C). The mixture was extracted with ethyl acetate
(200 mL). The organic layer was washed with brine, dried
(Na2SO4), and concentrated to a solid. The solid was dried
under high vacuum for 2 h. The crude solid material was
dissolved in 100 mL of 2-propanol by refluxing in a hot water
bath. Upon cooling the solution to À10 1C the product
crystallized. The mixture was vacuum-filtered, and the resulting
light brown crystals were dried under high vacuum (9.03 g,
filtered (Buchner funnel). The filter cake was washed with an
¨
additional 100 mL of water. The solid filtered material was
recrystallized from water/ethanol as follows. The solid filtered
material was transferred to a 250 mL round bottom flask
equipped with a reflux condenser. Water/ethanol (150 mL,
5 : 1) was added and the mixture was refluxed in a hot water
bath until all solid material had dissolved. Upon allowing the
solution to cool to room temperature the product crystallized.
The mixture was cooled to 4 1C for 2 h to promote more
crystallization. The mixture was vacuum-filtered and the
resulting off-white crystals were dried under high vacuum for
1
24 h (7.78 g, 80%): mp 140–143 1C; H NMR d 2.32 (s, 3H),
1
7.08 (d, J = 3.3 Hz, 1H), 9.60 (s, 1H), 9.95 (br s, 1H);
13C NMR d 9.8, 101.7, 126.0, 129.3, 131.7, 177.9; ESI-MS
obsd 187.9708, calcd 187.9706 [(M + H)+, M = C6H6BrNO].
82%): mp 85 1C; H NMR d 1.92 (s, 3H), 2.43 (s, 3H), 3.36
(t, J = 7.3 Hz, 2H), 4.54 (t, J = 7.3 Hz, 2H), 7.34 (d,
J = 8.4 Hz, 2H), 7.34 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H);
13C NMR d 10.5, 21.9, 24.3, 74.3, 105.2, 121.7, 124.3, 124.9,
126.9, 130.6, 135.6, 146.0; ESI-MS obsd 387.0024, calcd
387.0009 [(M + H)+, M = C14H15BrN2O4S].
4-Bromo-3-methyl-2-formyl-N-tosylpyrrole (3-Ts). Following a
general procedure,50 a stirred suspension of 60% NaH (2.5 g,
62 mmol) in dry THF (42 mL, distilled) was cooled to 0 1C
under argon. The mixture was treated portionwise with 3
(7.78 g, 41.4 mmol). The mixture was stirred for 30 min at
0 1C before treating all at once with p-toluenesulfonyl chloride
(8.00 g, 41.4 mmol). The reaction mixture was stirred at room
temperature for 3 h, whereupon water (100 mL) was slowly
added to quench the reaction. Ethyl acetate (100 mL) was
added, and the organic layer was separated. The organic layer
was washed with brine, dried (Na2SO4), and concentrated to a
solid. The solid was dried under high vacuum for 2 h. The
crude solid material was dissolved in 100 mL hexanes/ethyl
acetate (5 : 1) by refluxing in a hot water bath. Upon allowing
the solution to cool to room temperature the product
crystallized. The mixture was cooled overnight at À10 1C to
promote additional crystallization. The mixture was vacuum-
filtered, and the resulting light brown crystals were dried under
6-(4-Bromo-3-methyl-N-tosylpyrrol-2-yl)-1,1-dimethoxy-4,4-
dimethyl-5-nitrohexan-2-one (6-Ts). Following
a general
procedure,50 a mixture of 4-Ts (9.00 g, 23.3 mmol) and
1,1-dimethoxy-4-methyl-3-penten-2-one (11.1 g, 69.9 mmol,
3 equiv) was treated with DBU (10.5 mL, 69.9 mmol).
The reaction mixture was stirred for 15 min under argon.
A saturated solution of cold aqueous NH4Cl (50 mL, 0 1C)
was added. The mixture was extracted with ethyl acetate
(100 mL). The organic layer was washed with brine, dried
(Na2SO4), concentrated and dried overnight under high
vacuum. Addition of diethyl ether (50 mL) to the resulting
solid, trituration, and filtration afforded a pale brown solid
(11.0 g, 86%): mp 114–115 1C; 1H NMR d 1.22 (s, 3H), 1.27 (s,
2
3H), 1.85 (s, 3H), 2.42 (s, 3H), 2.64, 2.74 (AB, J = 19.0 Hz,
2
3
2H), 3.15 (ABX, JAB = 15.4 Hz, JBX = 1.8 Hz, 1H), 3.32
1
2
3
high vacuum (9.73 g, 69%): mp 152–155 1C; H NMR d 2.29
(ABX, JAB = 15.4 Hz, JAX = 11.7 Hz, 1H), 3.41 (s, 3H),
3.43 (s, 3H), 4.37 (s, 1H), 5.19 (ABX, 3JAX = 11.7 Hz, 3JBX
(s, 3H), 2.43 (s, 3H), 7.34 (d, J = 8.5 Hz, 2H), 7.55 (s, 1H),
7.76 (d, J = 8.5 Hz, 2H), 10.14 (s, 1H); 13C NMR d 2.1, 22.0,
106.2, 126.8, 127.6, 129.1, 130.6, 135.2, 136.4, 146.5, 180.1;
anal. calcd for C13H12BrNO3S: C, 45.63; H, 3.53; N, 4.09%.
found: C, 45.71; H, 3.44; N, 4.11%.
=
1.8 Hz, 1H), 7.28 (s, 1H), 7.31 (d, J = 8.1 Hz, 2H), 7.59 (d,
J = 8.1 Hz, 2H); 13C NMR d 10.7, 21.9, 23.8, 24.0, 25.9, 36.8,
44.2, 55.28, 55.29, 94.4, 104.9, 105.9, 122.6, 125.1, 125.9, 126.7,
130.5, 135.9, 145.6, 203.2; anal. calcd for C22H29BrN2O7S: C,
48.44; H, 5.36; N, 5.14%. Found: C, 48.70; H, 5.30; N, 5.17%.
4-Bromo-3-methyl-2-(2-nitroethyl)-N-tosylpyrrole
(4-Ts).
Following a general procedure,50 a stirred mixture of 3-Ts
(7.73 g, 28.5 mmol) in the form of a finely ground powder,
potassium acetate (2.24 g, 22.8 mmol), methylamine hydro-
chloride (1.54 g, 22.8 mmol), and acetic acid (0.1 mL) in
absolute ethanol (10 mL) was treated with nitromethane
(4.0 mL, 78 mmol). The mixture was stirred for 2 h, whereupon
water was added (100 mL) and the resulting yellow precipitate
was filtered by vacuum filtration. The solid filtered material
6-(4-Bromo-3-methyl-1H-pyrrol-2-yl)-1,1-dimethoxy-4,4-
dimethyl-5-nitrohexan-2-one (6-H). Following
a
general
procedure,50 a sample of 6-Ts (9.12 g, 16.7 mmol) was treated
with TBAF (34 mL, 1.0 M in THF, 34 mmol), and the reaction
mixture was stirred for 1 h at reflux. A saturated solution of
aqueous NaHCO3 (100 mL) was added followed by ethyl
acetate (50 mL). The mixture was extracted with ethyl acetate.
The organic layer was dried (Na2SO4), concentrated to a
c
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brown oil, dried under high vacuum for 2 h, and chromato-
graphed (silica, CH2Cl2) to give a light brown oil (4.00 g,
61%): 1H NMR d 1.13 (s, 3H), 1.22 (s, 3H), 1.95 (s, 3H), 2.60,
3,13-Diacetyl-2,8,8,12,18,18-hexamethylbacteriochlorin
(HBC-MeA). Following a procedure for replacement of a
bromo group with an acetyl group on a bacteriochlorin,45,58
a mixture of HBC-MeBr (40 mg, 0.072 mmol), tributyl-
(1-ethoxyvinyl)tin (100 mL, 0.288 mmol) and (PPh3)2PdCl2
(51 mg, 0.072 mmol) was refluxed in THF (7 mL) for 23 h
in a Schlenk flask. The reaction mixture was treated with 10%
aqueous HCl (40 mL) at room temperature for 10 min. The
reaction mixture was poured into a saturated aqueous solution
of NaHCO3 and extracted with dichloromethane. The organic
layer was dried (Na2SO4), concentrated and chromatographed
(silica, CH2Cl2) to give a purple solid (12 mg, 35%): 1H NMR
d À1.32 (br s, 2H), 1.94 (s, 12H), 3.19 (s, 6H), 3.61 (s, 6H), 4.39
(s, 4H), 8.59 (s, 2H), 9.35 (s, 2H); ESI-MS obsd 483.2755,
calcd 483.2755 [(M + H)+, M = C30H34N4O2]; labs (CH2Cl2)
359, 389, 523, 766 nm.
2
2
2.70 (AB, J = 18.8 Hz, 2H), 2.99 (ABX, JAB = 15.4 Hz,
3
=
2
3JBX = 2.5 Hz, 1H), 3.24 (ABX, JAB = 15.4 Hz, JAX
11.8 Hz, 1H), 3.41 (s, 3H), 3.42 (s, 3H), 4.38 (s, 1H), 5.12
(ABX, 3JAX = 11.8 Hz, 3JBX = 2.5 Hz, 1H), 6.59 (s, 1H), 8.29
(br s, 1H); 13C NMR d 9.8, 24.4, 24.4, 25.6, 36.6, 45.4, 55.39,
55.40, 94.1, 99.0, 104.7, 116.1, 116.7, 122.5, 204.2;
ESI-MS obsd 391.0864, calcd 391.0863 [(M + H)+, M =
C15H23BrN2O5].
3,13-Dibromo-5-methoxy-2,8,8,12,18,18-hexamethylbacterio-
chlorin (MeOBC-MeBr). Following a general procedure,46
a
solution of 1 (675 mg, 1.98 mmol, 18 mM) in anhydrous
CH2Cl2 (110 mL) was treated first with 2,6-DTBP (3.61 mL,
15.8 mmol, 144 mM) and second with TMSOTf (1.44 mL,
7.92 mmol, 72 mM). The reaction mixture was stirred at room
temperature for 16 h. The reaction mixture was concentrated,
and the residue was chromatographed [silica, hexanes/CH2Cl2
(1 : 1)]. A single green band was collected and concentrated to
a green solid (122 mg, 21%): 1H NMR d –1.99 (br s, 1H),
À1.78 (br s, 1H), 1.94 (s, 6H), 1.96 (s, 6H), 3.38 (s, 3H), 3.41 (s,
3H), 4.32 (s, 3H), 4.40 (s, 2H), 4.43 (s, 2H), 8.53 (s, 1H), 8.57
(s, 1H), 8.72 (s, 1H); 13C NMR d 13.0, 13.2, 31.2, 31.4, 45.9,
46.1, 47.6, 52.0, 64.5, 94.1, 94.4, 95.8, 106.8, 113.0, 125.7,
129.9, 131.8, 132.4, 133.8, 134.9, 160.9; ESI-MS obsd
585.0837, calcd 585.0859 [(M + H)+, M = C27H30Br2N4O];
labs (CH2Cl2) 351, 373, 502, 725 nm.
3,13-Diacetyl-15-bromo-5-methoxy-2,8,8,12,18,18-hexamethyl-
bacteriochlorin (MeOBC-MeA-Br15). A solution of MeOBC-MeA
(8.0 mg, 0.015 mmol) in THF (6.5 mL) was treated with NBS
(2.9 mg, 0.015 mmol, from 0.50 M freshly prepared THF stock
solution) at room temperature for 1 h. TLC analysis (silica,
CH2Cl2) showed the disappearance of starting material and the
presence of only one new spot. The reaction mixture was diluted
with CH2Cl2 and washed with saturated aqueous NaHCO3. The
organic layer was dried (Na2SO4), concentrated and chromato-
graphed (silica, CH2Cl2) to afford a green solid (6.2 mg, 70%):
1H NMR d À2.09 (br s, 1H), À1.87 (br s, 1H), 1.94 (s, 6H), 1.95
(s, 6H), 2.99 (s, 3H), 3.03 (s, 3H), 3.31 (s, 3H), 3.34 (s, 3H), 4.15
(s, 3H), 4.35 (s, 2H), 4.41 (s, 2H), 8.51 (s, 1H), 8.58 (s, 1H);
ESI-MS obsd 512.2782, calcd 512.2782 [(M À Br + H)+,
M = C31H35BrN4O3]; labs (CH2Cl2) 365, 376, 517, 726 nm.
3,13-Dibromo-2,8,8,12,18,18-hexamethylbacteriochlorin
(HBC-MeBr). Following a general procedure,44,46 a solution
of 1 (1.36 g, 3.99 mmol, 5 mM) in anhydrous CH3CN (800 mL)
was treated with BF3ÁOEt2 (4.9 mL, 40 mmol, 50 mM). The
reaction mixture was stirred at room temperature for 16 h.
Excess TEA (6.0 mL) was added to the reaction mixture. The
reaction mixture was concentrated, and the residue was
chromatographed [silica, hexanes/CH2Cl2 (1 : 1)] to afford a
3,13-Diacetyl-5,15-dibromo-2,8,8,12,18,18-hexamethylbacterio-
chlorin (BC-MeA-Br5,15). A solution of HBC-MeA (17 mg,
0.035 mmol) in THF (18 mL) was treated with NBS (6.3 mg,
0.035 mmol, from 0.50 M freshly prepared THF stock solution)
at room temperature for 1 h. TLC analysis (silica, CH2Cl2)
showed unreacted starting material and a new component.
The reaction mixture was diluted with CH2Cl2 and washed
with saturated aqueous NaHCO3. The organic layer was
dried (Na2SO4), concentrated and chromatographed (silica,
CH2Cl2). The first band (purple) was the remaining starting
bacteriochlorin (4.0 mg) and the second band (green) was the
(dibrominated) title compound (5.0 mg, 22%): 1H NMR
d À1.77 (br s, 2H), 1.94 (s, 12H), 3.04 (s, 6H), 3.32 (s, 6H),
4.42 (s, 4H), 8.56 (s, 2H); ESI-MS obsd 638.0887 and 559.1700,
1
green solid (139 mg, 13%): H NMR d À2.15 (br s, 2H), 1.96
(s, 12H), 3.40 (s, 6H), 4.46 (s, 4H), 8.60 (s, 2H), 8.87 (s, 2H);
ESI-MS obsd 555.0745, calcd 555.0753 [(M
+
H)+,
M = C26H28Br2N4]; labs (CH2Cl2) 346, 371, 491, 731 nm.
3,13-Diacetyl-5-methoxy-2,8,8,12,18,18-hexamethylbacterio-
chlorin (MeOBC-MeA). Following a procedure for replacement
of a bromo group with an acetyl group on a bacteriochlorin,45,58
a mixture of MeOBC-MeBr (82 mg, 0.14 mmol), tributyl-
(1-ethoxyvinyl)tin (195 mL, 0.56 mmol) and (PPh3)2PdCl2
(98 mg, 0.14 mmol) was refluxed in THF (14 mL) for 23 h in a
Schlenk flask. The reaction mixture was treated with 10%
aqueous HCl (40 mL) at room temperature for 10 min. The
reaction mixture was poured into a saturated aqueous solution of
NaHCO3 and extracted with dichloromethane. The organic layer
was dried (Na2SO4), concentrated and chromatographed [silica,
CH2Cl2/EtOAc (99:1)] to give a purple solid (23 mg, 32%):
1H NMR d À1.84 (br s, 1H), À1.55 (br s, 1H), 1.93 (s, 6H), 1.97
(s, 6H), 2.98 (s, 3H), 3.20 (s, 3H), 3.33 (s, 3H), 3.62 (s, 3H), 4.15
(s, 3H), 4.35 (s, 2H), 4.39 (s, 2H), 8.50 (s, 1H), 8.64 (s, 1H), 9.35
(s, 1H); ESI-MS obsd 513.2857, calcd 513.2860 [(M + H)+,
M = C31H36N4O3]; labs (CH2Cl2) 362, 523, 743 nm.
calcd 638.0892 and 559.1709 [(M)+ and (M
À
Br)+,
M = C30H32Br2N4O2]; labs (CH2Cl2) 359, 381, 518, 732 nm.
3-Acetyl-5-methoxy-2,8,8,12,18,18-hexamethylbacterio-131-
oxophorbine (MeOBOP). Following a reported procedure,53
a
mixture of MeOBC-MeA-Br15 (9.0 mg, 0.015 mmol), Cs2CO3
(25 mg, 0.077 mmol), and (PPh3)2PdCl2 (11 mg, 0.015 mmol)
was refluxed in toluene (1.6 mL) for 20 h in a Schlenk flask.
The reaction mixture was cooled to room temperature and
chromatographed [silica, CH2Cl2/THF (99 : 1)] to afford a
purple solid (6.6 mg, 86%): 1H NMR d À1.39 (br s, 1H),
0.12 (br s, 1H), 1.90 (s, 6H), 1.91 (s, 6H), 2.91 (s, 3H), 3.23
(s, 3H), 3.46 (s, 3H), 4.05 (s, 2H), 4.07 (s, 3H), 4.27 (s, 2H),
c
598 New J. Chem., 2011, 35, 587–601
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011

View Article Online
4.88 (s, 2H), 8.25 (s, 1H), 8.39 (s, 1H); ESI-MS obsd 511.2701,
calcd 511.2704 [(M + H)+, M = C31H34N4O3]; IR (NaCl) n,
cmÀ1 3435, 2954, 2918, 2850, 1687, 1630, 1360, 1226, 1132,
1084; labs (toluene) 359, 372, 530, 733 nm.
1649, 1423, 1217, 1149, 1095; labs (toluene) 359, 408, 544,
818 nm.
II Photophysical measurements
Static absorption and fluorescence measurements were
performed as described previously.69,70 Argon-purged solutions
of the samples in toluene with an absorbance of r0.10 at the
excitation wavelength were used for the fluorescence spectral,
quantum yield, and lifetime measurements. Fluorescence life-
times were obtained using a phase modulation technique and
Soret-band excitation70 or via decay measurements using
Soret-region excitation pulses obtained from a nitrogen-
pumped dye laser and time-correlated-single-photon-counting
detection. Emission measurements employed 2–4 nm excita-
tion- and detection-monochromator bandwidths and 0.2 nm
data intervals. Emission spectra were corrected for detection-
system spectral response. Fluorescence quantum yields were
determined relative to free base tetraphenylporphyrin
(Ff = 0.090),71 chlorophyll a in benzene (Ff = 0.325)72 or
chlorophyll a in toluene (which was found here to have the
same value as in benzene).
152-N-Benzyl-3-ethoxycarbonyl-2,12-diethyl-5-methoxy-
8,8,18,18-tetramethylbacteriochlorin-13,15-dicarboximide
(MeOBC-I). Following a reported procedure,54 a mixture of
MeOBC-EtEs-Br15 (7.7 mg, 0.011 mmol), Pd(PPh3)4 (13 mg,
0.011 mmol), and Cs2CO3 (11 mg, 0.034 mmol) was dried
under high vacuum in a Schlenk flask for 1 h. The flask was
then filled with CO and THF (1.5 mL) containing benzylamine
(5 mL, 0.05 mmol) was added. The reaction mixture was then
stirred at 80 1C for 20 h under a CO atmosphere. The reaction
mixture was cooled to room temperature and chromato-
graphed (silica, CH2Cl2) to afford a purple solid (4.8 mg,
1
62%): H NMR d À0.90 (br s, 1H), À0.43 (br s, 1H), 1.61 (t,
J = 7.2 Hz, 3H), 1.73 (m, 6H), 1.87 (s, 6H), 1.90 (s, 6H), 3.73
(q, J = 7.7 Hz, 2H), 4.15–4.28 (q, J = 7.2 Hz, 2H), 4.22
(s, 3H), 4.25 (s, 2H), 4.69 (s, 2H), 4.75 (q, J = 7.2 Hz, 2H),
5.67 (s, 2H), 7.32–7.44 (m, 3H), 7.74 (d, J = 7.4 Hz, 2H), 8.40
(s, 1H), 8.68 (s, 1H); ESI-MS obsd 688.3496, calcd 688.3493
[(M + H)+, M = C41H45N5O5]; IR (NaCl) n, cmÀ1 3435,
3386, 2959, 2919, 1728, 1682, 1647, 1537, 1215, 1149, 1126,
1088; labs (toluene) 351, 371, 407, 550, 793 nm.
III Density functional theory calculations
DFT calculations were performed with Spartan ’08 for
Windows version 1.2.0 in parallel mode73 on a PC equipped
with an Intel i7-975 cpu, 24 GB ram, and three 300 GB, 10k
rpm hard drives. The hybrid B3LYP functional and the
6-31G* set were employed. The equilibrium geometries were
fully optimized using the default parameters of the Spartan ’08
program.
15-Bromo-3,13-diethoxycarbonyl-2,12-diethyl-8,8,18,18-tetra-
methylbacteriochlorin (HBC-EtEs-Br15).
A
solution of
HBC-EtEs (50 mg, 0.088 mmol) in THF (35 mL) was treated
with NBS (16 mg, 0.088 mmol, from 0.50 M freshly prepared
THF stock solution) at room temperature for 1 h. The
reaction mixture was diluted with CH2Cl2 and washed
with saturated aqueous NaHCO3. The organic layer was
dried (Na2SO4), concentrated and chromatographed (silica,
Acknowledgements
This work was supported by grants from the Division of
Chemical Sciences, Geosciences and Biosciences Division,
Office of Basic Energy Sciences of the U.S. Department of
Energy to D.F.B. (DE-FG02-05ER15660), D.H. (DE-FG02-
05ER15661) and J.S.L. (DE-FG02-96ER14632). Mass spectra
were obtained at the Mass Spectrometry Laboratory for
Biotechnology at North Carolina State University. Partial
funding for the facility was obtained from the North Carolina
Biotechnology Center and the National Science Foundation.
1
CH2Cl2) to afford a green solid (10. mg, 18%): H NMR d
À1.61 (br s, 1H), À1.50 (br s, 1H), 1.60 (t, J = 7.2 Hz, 6H),
1.66–1.84 (m, 6H), 1.94 (s, 6H), 1.95 (s, 6H), 3.82 (q, J = 7.7 Hz,
2H), 4.15 (q, J = 7.4 Hz, 2H), 4.41 (s, 2H), 4.43 (s, 2H), 4.77
(m, 4H), 8.58 (s, 1H), 8.64 (s, 1H), 9.63 (s, 1H); ESI-MS obsd
649.2383, calcd 649.2384 [(M + H)+, M = C34H41BrN4O4];
labs (CH2Cl2) 354, 380, 520, 748 nm.
152-N-Benzyl-3-ethoxycarbonyl-2,12-diethyl-8,8,18,18-tetra-
methylbacteriochlorin-13,15-dicarboximide (HBC-I). Following a
reported procedure,54 a mixture of HBC-EtEs-Br15 (9.7 mg,
0.011 mmol), Pd(PPh3)4 (17 mg, 0.015 mmol), and Cs2CO3
(15 mg, 0.045 mmol) was dried under high vacuum in a Schlenk
flask. The flask was then filled with CO and THF (2.0 mL)
containing benzylamine (7 mL, 0.06 mmol) was added. The
reaction mixture was then stirred at 80 1C for 20 h under a
CO atmosphere. The reaction mixture was cooled to room
temperature and chromatographed (silica, CH2Cl2) to afford a
purple solid (4.0 mg, 44%): 1H NMR d À0.69 (br s, 1H), À0.47
(br s, 1H), 1.71 (m, 9H), 1.90 (s, 6H), 1.92 (s, 6H), 3.99–4.15 (q,
J = 7.2 Hz, 2H), 4.16–4.29 (q, J = 7.4 Hz, 2H), 4.33 (s, 2H), 4.72
(s, 2H), 4.77 (q, J = 7.2 Hz, 2H), 5.68 (s, 2H), 7.31–7.44 (m, 3H),
7.70–7.82 (m, 2H), 8.56 (s, 1H), 8.71 (s, 1H), 9.54 (s, 1H);
ESI-MS obsd 658.3399, calcd 658.3388 [(M + H)+, M =
C40H43N5O4]; IR (NaCl) n, cmÀ1 3431, 2956, 2918, 2848, 1680,
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