Nickel complexes of chlorophyll derivatives

Article abstract of DOI:10.1134/S1070363207070249

Nickel complexes of certain phorbine and amide derivatives of chlorophyll a were synthesized. Most of the chlorophyll a derivatives studied form nickel complexes when boiled in toluene with an equimolar amount of nickel acetylacetonate in high yield. The yields of the nickel complexes of the chlorophyll derivatives are determined by the stability of the starting ligand under the reaction conditions.

Full text of DOI:10.1134/S1070363207070249

ISSN 1070-3632, Russian Journal of General Chemistry, 2007, Vol. 77, No. 7, pp. 1300 1307.
Pleiades Publishing, Ltd., 2007.
Original Russian Text
pp. 1218 1225.
D.V. Belykh, I.S. Tarabukina, Yu.S. Matveev, A.V. Kuchin, 2007, published in Zhurnal Obshchei Khimii, 2007, Vol. 77, No. 7,
Nickel Complexes of Chlorophyll Derivatives
D. V. Belykh, I. S. Tarabukina, Yu. S. Matveev, and A. V. Kuchin
Institute of Chemistry, Komi Research Center, Ural Branch, Russian Academy of Sciences,
ul. Pervomaiskaya 48, Syktyvkar, 167982 Russia
e-mail: belykh-dv@chemi.komisc.ru
Received December 21, 2006
Abstract Nickel complexes of certain phorbine and amide derivatives of chlorophyll a were synthesized.
Most of the chlorophyll a derivatives studied form nickel complexes when boiled in toluene with an equimolar
amount of nickel acetylacetonate in high yield. The yields of the nickel complexes of the chlorophyll deri-
vatives are determined by the stability of the starting ligand under the reaction conditions.
DOI: 10.1134/S1070363207070249
1
Natural porphyrins and their modified analogs find
wide application in medicine for diagnostics and
treatment of oncological diseases [1, 2]. It was fairly
recently found that nickel and zinc complexes of some
chlorophyll a derivatives act as photo-independent
cytotoxic agents with respect to malignant cells [3].
In this work we synthesized a series of nickel com-
plexes by reactions of natural chlorins with nickel
acetate and acetylacetonate under various conditions.
confirmed by the H NMR data and by its reaction
1
with methyl- and dimethylamine. The H NMR spec-
trum of the product can be interpreted as a superposi-
tion of the spectra of two compounds, and, therewith,
the superimposed spectra are identical by the number
and multiplicity of signals and differ by the chemical
shifts of the signals. The greatest difference is in the
chemical shifts of the signals of the protons in posi-
tion 13(2). Under the action of dimethyl- and methyl-
amine, the product gives complexes IX and X, res-
pectively. The formation of amide complexes as
single reaction products provides evidence for the
To synthesize nickel complexes, we used chloro-
phyll a phorbine and amide derivatives I V obtained
by published procedures [4 6]. To synthesize nickel
complexes VI X, we studied the reaction of these
chlorins with nickel acetate and acetylacetonate under
various conditions (see scheme and table).
1
conclusion based on the H NMR data.
Tertiary 13-amides of chlorin e6 are known to exist
in the form of two atropoisomers (see scheme) in
equilibrium with each other [5]. The same is true of
complex IX. Compared to starting ligand IV, the ratio
of atropoisomers in the complex is different (Fig. 2).
The change in the isomeric ratio in the equilibrium
mixture seems to be connected with a change in the
macrocycle conformation on introduction of the metal
into the chlorin coordination sphere. The change of
the macrocycle conformation changes the relative
stability of the atropoisomers and, as a result, their
contents in the equilibrium mixture.
The structure of the resulting complexes was
1
proved by means of electronic and H NMR spec-
troscopy. Comparison of the electronic absorption
spectra of the ligands and their nickel complexes
shows that the maximum of band I in the spectrum
of the complex is shifted by 10 30 nm to the short-
wave region, implying that nickel enters in the chlorin
coordination sphere. The 1H NMR spectra of the
complexes contain signals of the same groups as the
spectra of the starting ligands, except for the NH
proton signals of the porphyrin cycle. As follows from
Nickel complexes are most commnly synthesized
using nickel acetate taken in a great excess. The reac-
tion with nickel acetate is carried out either in a mix-
ture of chloroform with methanol or in glacial acetic
acid. When the reaction is carried out in glacial acetic
acid, nickel complexes are formed only on boiling.
1
the H NMR spectrum of complex VI (Fig. 1), the
reaction of compound I with nickel acetylacetonate
involves, along with complex formation, isomeriza-
tion of the ligand in the 13(2) position, leading to enol
XI as intermediate. As a result, a mixture of diastereo-
isomeric Ni-methylpheophorbid a (VI) and Ni-methyl-
pheophorbid a (XII) was obtained. The fact that the
product of the reaction between nickel acetylacetonate
and compound I is a mixture of diastereoisomers is
As seen from the table, high yields of nickel com-
plexes are obtained only with fairly stable ligands II
and III. With amides IV and V, the yields are much
1300

NICKEL COMPLEXES OF CHLOROPHYLL DERIVATIVES
1301
3(2)
3(1)
7(1)
5
3
4
6
7
8
8(1)
8(2)
2(1)
I
II
2
1
N
N
N
NH
N
9
Ni2+
10
20
Ni
R1
Ni(OAc)2, Ni (AcAc)2
19
18
11
N
N
HN
12(1)
III
IV
16
15
12
14
17
18(1)
17(2)
13
R2
R2
R1
17(1)
CO2CH3
CO2CH3
17(3) 17(4)
I V
VI X
R3
14
R3
H N
13
15
CH3
14
15
13(2)
N
13
15(1)
13(1)
CH3
O
CO2CH3
O
CO2CH3
CO2CH3
CO2CH3
VI
IX, X
14
14
15
13(2)
15
13(2)
13
13
13(1)
13(1)
OH
O
CO2CH3
CO2CH3
CO2CH3
CO2CH3
XI
XII
N
N
N
N
N
M
M
N
N
N
O
O
C
C
CO2CH3
CO2CH3
CO2CH3
N(CH3)2
N(CH3)2
CO2CH3
IV
IX
M = H2 (IV), Ni (IX). For R1 and R2, see table, R3 = CH3 (IX), H (X).
lower. With compound I, no nickel complex forms
under these conditions. Complex VI could be ob-
tained with 10% yield by boiling compound I in to-
luene with an equimolar amount of nickel acetylace-
tonate. Under these conditions, the yields of other
complexes also increase, especially strongly with re-
latively labile ligands II and III.
in the complex-formation reaction and also by the
stability of the ligands under the reaction conditions.
The stability of a ligand is determined by its reactivity
in all reactions except for complex formation (un-
desirable side reactions). The tendency for various
undesirable reactions can be predicted on the basis of
available information on the chemistry of chlorophyll
derivatives. Compound I containing a reactive exo
cycle is known to be most labile of all the ligands
used, whereas compounds II and III are the most
The preparative yields of the complexes are most
affected by the reactivity of the ligands and metal salt
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 7 2007

1302
BELYKH et al.
Yields of nickel complexes (VI X), %
Starting
Complex
ligand
CH3COOH,
Ni(CH3COO)2
Toluene,
Ni(AcAc)2
R2
R1
I
VI
0
60
45
25
21
10
65
78
69
70
O
CO2CH3
II
III
IV
V
VII
VIII
IX
HO
O
CO2CH3
O
CH3
CH3
N
C
O
CO2CH3
X
CH3
CH3
N
C
CO2CH3
O
stable. In their stability, chlorins IV and V occupy an
intermediate position between methylpheophorbid I
and phorbine derivatives II and III. The activated
methylene group in position 15(1) of molecules IV
and V can take part in many reactions similar to re-
actions of the 13(2)-methine group in compound I,
but the reactivity of the 15(1)-methylene groups in
chlorins IV and V is essentially lower. Summarizing
the data in the table, we note that the preparative yield
of natural chlorin complexes is most affected by the
stability of the ligands under the reaction conditions.
The highest yields of complexes were obtained with
compounds II and III and the lowest, with com-
pound I.
also be obtained by the action of amines on complex
VI. However, this synthetic approach is less effective
because of the difficulties in preparation of complex
VI. Similar difficulties also arise when complex VI is
converted to complex VIII.
EXPERIMENTAL
1
The H NMR spectra were recorded in deutero-
chloroform on Bruker AMX-400 (400 MHz) and
TESLA BS 587A (80 MHz) instruments. The IR spec-
tra were recorded on a Specord M-80 device in KBr.
The electronic absorption spectra were recorded on a
Shimadzu UV-1700 spectrometer (PharmaSpec) at
200 1100 nm in quartz cells 10 mm in thickness with
chloroform as reference. Thin-layer chromatography
was performed on Silufol plates, eluent CCl4 acetone
(4:1 v/v). Silica gel of 100/400 grade (Silica gel L,
wet packing) was used for column chromatography.
The fact that higher yields of complexes are at-
tained on boiling in toluene is explained by the use of
a more inert (compared to acetic acid) solvent. Re-
placement of toluene by benzene that has a lower
boiling point provides a higher yield (30%) of com-
plex VI. However, with benzene, we failed to achieve
complete conversion of the starting ligand, which
essentially complicated isolation of the complex.
Therefore, with more stable ligands, with which the
yields of complexes are sufficiently high, such re-
placement is inexpedient. Complexes IX and X can
Methylpheophorbid a (I) was prepared from
nettle [4]. Electronic absorption spectrum (CHCl3), ,
nm: 668, 610, 541, 514, and 416 (Soret band). IR
1
spectrum (KBr), cm : 1624 (chlorin band), 1746
(
C=O, ester), 1706 ( C=O, keto group in the exo cycle).
1H NMR spectrum (CDCl3, 80 MHz), , ppm: 9.42 s
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 7 2007

NICKEL COMPLEXES OF CHLOROPHYLL DERIVATIVES
(a)
1303
N
NH
N HN
6.40 6.30 6.20 6.10 6.00 5.90 5.80 5.70 5.60
O
CO2CH3
CO2CH3
I
9.4 9.2 9.0 8.8 8.6 8.4 8.2 8.0 7.8 7.6 7.4 7.2 7.0 6.8 6.6 6.4 6.2 6.0 5.8 5.6
, ppm
(b)
N
N
N
Ni
N
6.40 6.30 6.20 6.10 6.00 5.90 5.80 5.70 5.60
13(2)
O
CO2CH3
CO2CH3
VI
9.4 9.2 9.0 8.8 8.6 8.4 8.2 8.0 7.8 7.6 7.4 7.2 7.0 6.8 6.6 6.4 6.2 6.0 5.8 5.6
, ppm
1
Fig. 1. H NMR spectrum of (a) methylpheophorbid a (I) and (b) its nickel complex VI (CDCl , 400 MHz).
3
(1H, H10), 9.30 s (1H, H5), 8.55 s (1H, H20), 7.92 d.d
[1H, 3-(CH=CH2), J 17.0 and 12.0 Hz], 6.27 s [1H,
H13(2)], 6.20 br.d [1H, 3-(CH=CHHtrans), J 16.0 Hz],
6.12 br.d [1H, 3-(CH=CHHcis) J 12.0 Hz], 4.1 4.5 m
(2H, H17, H18), 3.91 s [3H, 17-(CH2CH2COOCH3)],
3.61 s (3H, 12-CH3), 3.32 s (3H, 2-CH3), 3.00 s (3H,
7-CH3), 3.8 3.4 m [2H, 8-(CH2CH3)], 2.2 2.8 m [4H,
17-(CH2CH2COOCH3)], 1.84 d (3H, 18-CH3, J
10 Hz), 1.58 t (3H, 8-CH2CH3, J 12 Hz), 0.51 br.s
(1H, I-NH), 1.8 br.s (1H, III-NHNH).
3-(CH=CHHcis) J 12.0 Hz], 5.43 s (1H, 132-OH),
4.50 q (1H, H18, J 8.0 Hz), 4.16 br.d (1H, H17, J
8.1 Hz), 3.68 s (3H, 132-COOCH3), 3.67 s (3H,
12-CH3), 3.63 s [1H, 17-(CH2CH2COOCH3)], 3.57 s
(3H, 2-CH3), 3.32 s (3H, 7-CH3), 3.40 q [2H,
8-(CH2CH3),
J
8.0 Hz], 2.23 2.65
m
[4H,
17-(CH2CH2COOCH3)], 1.56 t [3H, 8-(CH2CH3), J
8.0 Hz)], 1.61 d (3H, 18-CH3, J 8.0 Hz), 0.20 br.s
(1H, I-NH), 1.98 (br.s 1H, III-NHNH); minor
isomer, 9.30 s (1H, H10), 9.13 s (1H, H5), 8.58 s (1H,
H20), 7.79 d.d [1H, 3-(CH=CH2), J 16.0 and 12.0 Hz],
6.14 d [1H, 3-(CH=CHHtrans), J 16.0 Hz], 6.05 [1H,
3-(CH=CHHcis) J 12.0 Hz], 5.27 s (1H, 132-OH),
4.50 q (1H, H18, J 8.0 Hz), 4.16 br.d (1H, H17, J
8.1 Hz), 3.68 s (3H, 132-COOCH3), 3.66 s [3H,
17-(CH2CH2COOCH3)], 3.62 s (3H, 12-CH3), 3.56 s
(3H, 2-CH3), 3.32 s (3H, 7-CH3), 3.40 q [2H,
(132-Hydroxy)methylpheophorbid a (II) was
isolated by column chromatography on silica gel (with
subsequent crystallization from chloroform methanol)
from the fraction of polar chlorophyll derivatives ob-
tained on isolation of compound I. The mixture
contained diastereoisomers differing in the configura-
tion of the asymmetric carbon atom in position 13(2).
Electronic absorption spectrum (CHCl3), , nm: 669,
8-(CH2CH3),
J
8.0 Hz], 2.23 2.65
m
[4H,
17-(CH2CH2COOCH3)], 1.56 t [3H, 8-(CH2CH3), J
8.0 Hz)], 1.71 d (3H, 18-CH3, J 8.0 Hz), 0.24 br.s
(1H, I-NH), 1.98 br.s (1H, III-NHNH).
1
609, 535, 505, 414 (Soret band). H NMR spectrum
(CDCl3, 400 MHz), , ppm: major isomer, 9.37 s (1H,
H10), 9.15 s (1H, H5), 8.60 s (1H, H20), 7.79 d.d [1H,
3-(CH=CH2), J 20.0 and 12.0 Hz], 6.14 d [1H, 3-
Methylpyropheophorbid a (III). A solution of
200 mg of compound I in 6 ml of pyridine was boiled
(CH=CHHtrans),
J
20.0 Hz], 6.05
d
[1H,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 7 2007

1304
BELYKH et al.
(a)
100.0
170.5
NH N
N HN
9.00
8.80
8.60
8.40
9.2
8.20
8.00
7.80
C=O
N(CH3)2
CO2CH3
CO2CH3
IV
9.8
113.6
9.6
100.0
9.4
9.0
8.8
8.6
(b)
8.4
8.2
8.0
7.8
7.6
, ppm
N
N
N
N
Ni
C O
8.15 8.10 8.05 8.00 7.95 7.90 7.85 7.80 7.75 7.70
N(CH3)2
CO2CH3
CO2CH3
IX
9.8
9.6
9.4
9.2
9.0
8.8
8.6
8.4
8.2
8.0
7.8
7.6
, ppm
1
Fig. 2. H NMR spectrum of (a) 13-N,N-dimethylamide-15,17-dimethyl ester of chlorin e (IV) and (b) its nickel complex IX
6
(CDCl , 400 MHz).
3
for 5 h, the mixture was cooled, mixed with 150 ml
of chloroform, pyridine was removed with 5 7% HCl,
and excess acid was removed with water. The chloro-
form solution was dried with anhydrous sodium
sulfate and evaporated. The residue was subjected to
column chromatography on (eluent CCl4 acetone,
60:1). Yield 175 mg (97%). Electronic absorption
COOCH3)], 1.80 d (3H, 18-CH3, J 7.0 Hz), 1.64 (3H,
8-CH2CH3, J 12.0 Hz), 0.80 br.s (1H, I-NH), 1.78
br.s (1H, III-NHNH).
13-(N,N-Dimethylamide)-15,17-dimethyl ester of
chlorin e6 (IV). Dimethylamine, 1 ml of a 33%
aqueous solution, was added to a solution of 120 mg
of compound I in 3 ml of chloroform. The reaction
mixture was stirred for 1 h, diluted with chloroform,
transferred to a separatory funnel, and the residual
dimethylamine was washed off with distilled water to
neutral washings. The resulting solution was dried
with anhydrous sodium sulfate, the solvent was dis-
tilled off, and the residue was subjected to column
chromatography. Yield 70 mg (55%). Electronic ab-
sorption spectrum (CHCl3), , nm: 663, 607, 557,
spectrum (CHCl3), , nm: 668, 611, 535, 506, 417
1
(Soret band). IR spectrum (KBr), cm : 1745 (
,
ester, the intensity of the band is much lower thanCth=Oat
of the same band of compound I), 1702 ( C=O, keto
group in the exo cycle), 1610 (chlorin band). 1H NMR
spectrum (CDCl3, 80 MHz), , ppm: 9.37 s (1H, H10),
9.27 s (1H, H5), 8.52 s (1H, H20), 7.95 d.d [1H,
3-(CH=CH2), J 19.0 and 11.0 Hz], 6.23 d [1H,
3-(CH=CHHtrans),
J
18.0 Hz], 6.13
d
[1H,
1
529, 501, 402. IR spectrum (KBr), cm : 1630 (chlo-
3-(CH=CHHcis) J 10.0 Hz], 5.30 d (1H, H13(2),A, J
1
rin band, 1732 ( C=O, ester), 1653 (amide I band). H
22.0 Hz), 5.05 d [1H, H13(2),B, J 21.0 Hz], 4.1 4.6 m
(2H, H18, H17), 3.7 m [2H, 8-(CH2CH3)], 3.61 s [6H,
12-CH3, 17-(CH2CH2COOCH3)], 3.37 s (3H, 2-CH3),
3.14 s (3H, 7-CH3), 2.10 2.80 m [4H, 17-(CH2CH2
NMR spectrum (CDCl3, 80 MHz), , ppm: major
isomer, 9.69 s (1H, H10), 9.66 s (1H, H5), 8.88 s (1H,
H20), 8.21 d.d [1H, 3-(CH=CH2), J 17.9 and 11.5 Hz],
6.33 d.d [1H, 3-(CH=CHHtrans), J 19.6 and 1.8 Hz],
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 7 2007

NICKEL COMPLEXES OF CHLOROPHYLL DERIVATIVES
1305
6.05 d.d [1H, 3-(CH=CHHcis) J 11.5 and 1.6 Hz],
5.73 d (1H, H15(1),A, J 19.0 Hz), 5.04 d (1H, H15(1),B
8.77 g of Ni(NO3)2 6 H2O in 70 ml of distilled water.
The mixture was stirred at room temperature until the
reagents dissolved completely. Ammonium solution
was then added dropwise with stirring to pH 7.5. The
light green precipitate that formed was filtered off,
dried in vacuum (yield 9.54 g), and recrystallized
from alcohol (light green crystals). The crystals are
suitable for X-ray diffraction analysis. IR spectrum
,
J 19.0 Hz), 4.40 4.60 m (2H, H17, H18), 3.97 s [3H,
15-(CH2COOCH3)], 3.75 s [3H, 17-(CH2CH2COO
CH3)], 3.62 s (3H, 12-CH3), 3.48 s (3H, 2-CH3),
3.31 s (3H, 7-CH3), 3.49 s [3H, 13-C(O)N(CH3)(CH3)],
2.72 s [3H, 13-(O)N(CH3)(CH3)], 3.68 3.85 m [2H,
8-(CH2CH3)], 2.10 2.70 m [4H, 17-(CH2CH2COO
CH3)], 1.60 1.75 m (6H, 18-CH3, 8-CH2CH3), 1.75
br.s (I-NH), 1.91 br.s (III-NHNH); minor isomer,
9.67 s (1H, H10), 9.63 s (1H, H5), 8.77 s (1H, H20),
7.99 d.d [1H, 3-(CH=CH2), J 17.7 and 11.5 Hz],
6.33 d.d [1H, 3-(CH=CHHtrans), J 19.6 and 1.8 Hz],
6.05 d.d [1H, 3-(CH=CHHcis) J 11.5 and 1.6 Hz],
1
(KBr), cm : 3353 ( O H), 3276, 2992, 1620 ( C=O),
1522 ( C O), 1464, 1406, 1256, 1213, 1017, 928,
764, 660, 569 ( M O). Found after decomposition with
nitric acid, %: Ni 20.68. C5H8NiO2 H2O. Calculated,
%: Ni 21.27.
Nickel complexes of chlorophyll derivatives.
a. Starting ligand was boiled for 30 min with an
equimolar amount of nickel acetate in glacial acetic
acid. The formation of the reaction product was con-
trolled by TLC on Silufol plates (CCl4 acetone, 4:1).
When the reaction was complete, the mixture was
diluted with chloroform, and the acid and excess
nickel acetate were washed off with distilled water to
neutral washings. The resulting solution was dried
with anhydrous sodium sulfate, and the solvent was
distilled off under reduced pressure. The resulting
complex was isolated by column chromatography.
5.57 d (1H, H15(1),A, J 19.0 Hz), 5.13 d (1H, H15(1),B
,
J 19.0 Hz), 4.40 4.60 m (2H, H17, H18), 3.97 s [3H,
15-(CH2COOCH3)], 3.74 s [3H, 17-(CH2CH2COO
CH3)], 3.59 s (3H, 12-CH3), 3.45 s (3H, 2-CH3),
3.31 s (3H, 7-CH3), 3.49 [3H, C(O)N(CH3)(CH3)],
3.08 s [3H, C(O)N(CH3)(CH3)], 3.68 3.85 m [2H,
8-(CH2CH3)], 2.10 2.70
m
[4H, 17-(CH2CH2
COOCH3)], 1.60 1.75 m (6H, 18-CH3, 8-CH2CH3),
1.65 br.s (I-NH), 1.73 br.s (III-NHNH).
13-(N-Methylamide)-15,17-dimethyl ester of
chlorin e6 (V). Methylamine, 0.8 ml of a 33%
aqueous solution, was added to a solution of 146 mg
of compound I in 8 ml of THF. The reaction mixture
was stirred for 30 min, diluted with chloroform, the
residual methylamine was washed off with distilled
water to neutral washings. The resulting solution was
dried with anhydrous sodium sulfate, and the solvent
was distilled off. The residue was subkected to
column chromarography. Yield 110 mg (72%). Elec-
tronic absorption spectrum (CHCl3), , nm: 663, 607,
b. Starting ligand was boiled for 3 h with an
equimolar amount of nickel acetylacetonate in toluene.
The formation of the reaction product was controlled
by TLC. The resulting complex was isolated by
column chromatography. The mixture to be separated
was applied on the column directly from the reaction
mixture without its pretreatment. The reaction of
compound I with nickel acetylacetonate in benzene
was carried out similarly.
1
Ni-(132-Hydroxy)methylpheophorbid
a
(VII).
557, 529, 500, 402. IR spectrum (KBr), cm : 1608
(chlorin band), 1744 ( C=O, ester), 1636 (amide I
a. From 222 mg of compound II and 64 mg of nickel
acetate, 145 mg (60%) of complex VII was obtained.
Electronic absorption spectrum (CHCl3), , nm: 652,
1
band). H NMR spectrum (CDCl3, 400 MHz), , ppm:
9.70 s (1H, H10), 9.64 s (1H, H5), 8.81 s (1H, H20),
8.10 d.d [1H, 3-(CH=CH2), J 23.8 and 15.4 Hz], 6.37
d.d [1H, 3- (CH=CHHtrans), J 23.8 and 1.8 Hz], 6.15
d.d [1H, 3-(CH=CHHcis), J 15.8 and 1.8 Hz], 6.40 m
(1H, 13-CONHCH3), 5.54 d (1H, H15(1),A, J 25.0 Hz),
1
610, 542, 495, 422, 394. H NMR spectrum (CDCl3,
400 MHz), , ppm: major isomer, 9.26 s (1H, H10),
9.01 s (1H, H5), 8.22 s (1H, H20), 7.72 d.d [1H,
3-(CH=CH2), J 18.0 and 12.0 Hz], 6.00 d [1H,
5.26 d (1H, H15(1),B, J 25.0 Hz), 4.36 4.49 m (2H,
H17, H18), 3.84 s (3H, 132-COOCH3), 3.62 s [3H,
17-(CH2CH2COOCH3)], 3.56 s (3H, 12-CH3), 3.50 s
(3H, 2-CH3), 3.33 s (3H, 7-CH3), 3.81 q [2H,
8-(CH2CH3) J 10.0 Hz], 3.24 d (3H, 13-CONHCH3,
J 5.6 Hz), 1.90 2.60 m [4H, 17-(CH2CH2COOCH3)],
1.73 m (6H, 18-CH3, 8-CH2CH3), 1.60 br.s (I-NH),
1.80 br.s (III-NHNH).
3-(CH=CHHtrans),
J
18.0 Hz], 5.97
d
[1H,
3-(CH=CHHcis), J 12.0 Hz], 5.10 s (1H, 132-OH),
4.26 4.32 m (2H, H17, H18), 3.78 s (3H, 132-
COOCH3), 3.64 s [3H, 17-(CH2CH2COOCH3)],
3.50 s (3H, 12-CH3), 3.15 s (3H, 2-CH3), 3.00 s (3H,
7-CH3), 3.42 3.58 m [2H, 8-(CH2CH3)], 2.19 2.46 m
[4H, 17-(CH2CH2COOCH3)], 1.53 t (3H, 8-CH2CH3,
J 8.0 Hz), 1.42 d (3H, 18-CH3, J 10.0 Hz); minor
isomer, 9.22 s (1H, H10), 8.98 s (1H, H5), 8.18 s (1H,
H20), 7.72 d.d [1H, 3-(CH=CH2), J 18.0 and 12.0 Hz],
6.00 d. [1H, 3-(CH=CHHtrans), J 18.0 Hz], 5.97 d
Nickel acetylacetonate was obtained by precipita-
tion from aqueous solution [7]. Distilled (137 C)
acetylacetone, 6.5 ml, was added to a solution of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 7 2007

1306
BELYKH et al.
[1H, 3-(CH=CHHcis), J 12.0 Hz], 5.16 s (1H,
132-OH), 4.26 4.32 m (2H, H17, H18), 3.78 s (1H,
132-CO2CH3), 3.64 s [3H, 17-(CH2CH2COOCH3)],
3.48 s (3H, 12-CH3), 3.14 s (3H, 2-CH3), 3.00 s (3H,
7-CH3), 3.42 3.58 m [2H, 8-(CH2CH3)], 2.19 2.46 m
[4H, 17-(CH2CH2COOCH3)], 1.53 t (3H, 8-CH2CH3,
J 8.0 Hz), 1.42 d (3H, 18-CH3, J 8.0 Hz).
[4H, 17-(CH2CH2COOCH3)], 1.53 1.70 m (3H,
8-CH2CH3), 1.48 d (3H 18-CH3, J 8.0 Hz); minor
isomer: 9.09 s (1H, H10), 9.02 s (1H, H5), 8.02 s (1H,
H20), 7.78 d.d [1H, 3-(CH=CH2), J 18.8 and 8.0 Hz],
6.03 m [1H, 3-(CH=CHHtrans)], 5.90 br.d [1H,
3-(CH=CHHcis) J 12.0 Hz], 4.15 4.08 m [2H,
15-(CH2CO2CH3)], 4.09 m (1H, H18), 3.89 3.92 m
(1H, H17), 3.69 s [3H, 15-(CH2COOCH3)], 3.65 s
[3H, 17-(CH2CH2COOCH3)], 3.37 s (3H, 12-CH3),
3.13, 3.11 both br.s [both 6H, 2-CH3, 12-CH3, 7-CH3,
13-C(O)N(CH3)(CH3)], 2.96 s [3H, 13-C(O)N(CH3)
(CH3)], 3.47 3.60 m [2H, 8-(CH2CH3)], 2.03 2.50 m
[2H, 17-(CH2CH2COOCH3)], 1.53 1.70 m (3H,
8-CH2CH3), 1.44 d (3H, 18-CH3, J 8.0 Hz).
b. From 19 mg of compound II and 9 mg of nickel
acetylacetonate, 14 mg (65%) of complex VII was
obtained. The complexes obtained by procedures a
and b coincide in chromatographic mobility (TLC)
and spectral characteristics.
Ni-methylpyropheophorbid a (VIII). a. From
34 mg of compound III and 12 mg of nickel acetate,
17 mg (45%) of complex VIII identical to the sample
prepared by procedure b was obtained.
Ni-(13-N-methylamide)-15,17-dimethyl ester of
chlorin e6 (Ni V). a. From 28 mg of compound V
and 8 mg of nickel acetate, 6 mg (21%) of complex
X identical to the sample prepared by procedure b was
obtained.
b. From 29 mg of compound III and 15 mg of
nickel acetylacetonate, 25 mg (78%) of complex VIII
was obtained. Electronic absorption spectrum (CHCl3),
1
, nm: 652, 607, 543, 501, 422, 397. H NMR spec-
trum (CDCl3, 400 MHz), , ppm: 9.30 s (1H, H10),
9.06 s (1H, H5), 8.16 s (1H, H20), 7.77 d.d [1H,
3-(CH=CH2), J 16.0 and 8.0 Hz], 6.03 d.d [1H,
3-(CH=CHHtrans), J 16.0 and 2.0 Hz], 5.97 d.d [1H,
3-(CH=CHHcis) J 12.0 and 2.0 Hz], 4.87 d (1H,
b. From 29 mg of compound V and 13 mg of
nickel acetylacetonate, 22 mg (70%) of complex X
was obtained. Electronic absorption spectrum (CHCl3),
1
, nm: 634, 497, 409. H NMR (CDCl3, 400 MHz),
, ppm: 9.09 s (1H, H10), 9.03 s (1H, H5), 8.03 s (1H,
H13(2),A, J 22.0 Hz), 4.79 d (1H, H13(2),B, J 21.0 Hz),
3.97 4.01 m 18, (1H, H17), 4.28 q (1H, J 8.0 Hz),
3.60 s [3H, 17-(CH2CH2COOCH3)], 3.48 s (3H,
12-CH3), 3.15 s (3H, 2-CH3), 3.12 s (3H, 7-CH3),
3.58 3.61 m [2H, 8-(CH2CH3)], 2.06 2.48 m [4H,
17-(CH2CH2COOCH3)], 1.53 1.62 m (6H, 18-CH3,
8-CH2CH3).
H20), 7.79 d.d [1H, 3-(CH=CH2), J 17.0 and 12.0 Hz],
6.02 d.d [1H, 3-(CH=CHHtrans), J 17.0 and 2.0 Hz],
5.93 d.d [1H, 3-(CH=CHHcis), J 12.0 and 2.0 Hz],
6.22 br.q (1H, 13-CONHCH3, J 4.8 Hz), 4.91 d (1H,
H
15(1),A, J 20.0 Hz), 4.50 d (1H, H15(1),B, J 20.0 Hz),
4.11 q (1H, H18, J 7.2 Hz), 3.94 3.97 m (1H, H17),
3.82 [3H, 15-(CH2COOCH3)], 3.64 [1H,
s
s
Ni-(13-N,N-dimethylamide)-15,17-dimethyl ester
of chlorin e6 (IX). a. From 34 mg of compound IV
and 10 mg of nickel acetate, 9 mg (25%) of complex
IX identical to the sample prepared by procedure b
was obtained.
17-(CH2CH2COOCH3)], 3.20 s (3H, 12-CH3), 3.18 d
(3H, 13-CONHCH3, J 5.2 Hz), 3.12 s (3H, 2-CH3),
3.11 s (3H, 7-CH3), 3.25 3.50 m [2H, 8-(CH2CH3)],
2.27 2.50 m [4H, 17-(CH2CH2COOCH3)], 1.54
1.58 m (3H, 8-CH2CH3), 1.46 d (3H, 18-CH3, J
7.2 Hz).
b. From 20 mg of compound IV and 9 mg of
nickel acetylacetonate, 15 mg (69%) of complex IX
was obtained. Electronic absorption spectrum (CHCl3),
Mixture of diastereoisomeric Ni-methylpheo-
phorbid a (VI) and Ni-methylpheophorbid a (XII).
From 78 mg of compound I and 33 mg of nickel
acetylacetonate, 9 mg (10%) of a mixture of stereo-
isomeric complexes VI and XII was obtained. Elec-
tronic absorption spectrum (CHCl3), , nm: 652, 539,
496, 416. 1H NMR (CDCl3, 400 MHz), , ppm:
complex VI: 9.31 s (1H, H10), 9.07 s (1H, H5), 8.17 s
(1H, H20), 7.75 d.d [1H, 3-(CH=CH2), J 17.5 and
12.0 Hz], 6.02 d.d [1H, 3-(CH=CHHtrans), J 17.6 and
1.6 Hz], 5.98 d.d [1H, 3-(CH=CHHcis), J 12.0 and
2.0 Hz], 5.79 s (1H, H13(2)), 4.20 4.28 m (2H, H17,
H18), 3.91 s (3H, 132-CO2CH3), 3.58 s [3H,
1
, nm: 642, 495, 402. H NMR (CDCl3, 400 MHz),
, ppm: major isomer, 9.11 s (1H, H10), 9.04 s (1H,
H5), 8.06 s (1H, H20), 7.80 d.d [1H, 3-(CH=CH2),
J 18.8 and 8.0 Hz], 6.03 m [1H, 3-(CH=CHHtrans)],
5.90 br.d [1H, 3-(CH=CHHcis) J 12.0 Hz], 5.26 d (1H,
H15(1),A , J 19.0 Hz), 4.48 d (1H, H15(1),B, J 19.0 Hz),
4.06 4.09 m (1H, H18), 3.89 3.92 m (1H, H17),
3.90
s
[3H, 15-(CH2COOCH3)], 3.63 s [3H,
17-(CH2CH2COOCH3)], 3.34 s (3H, 12-CH3), 3.13,
3.11 both br.s [both 6H, 2-CH3, 12-CH3, 7-CH3,
13-C(O)N(CH3)(CH3)], 2.94 s [3H, 13-C(O)N(CH3)
(CH3)], 3.47 3.60 m [2H, 8-(CH2CH3)], 2.03 2.50 m
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NICKEL COMPLEXES OF CHLOROPHYLL DERIVATIVES
1307
17-(CH2CH2COOCH3)], 3.48 s (3H, 12-CH3), 3.15 s
REFERENCES
(3H, 2-CH3), 3.12 s (3H, 7-CH3), 3.54 3.65 m [2H,
8-(CH2CH3)], 2.06 2.42 m [4H, 17-(CH2CH2COO
CH3)], 1.45 1.62 m (6H, 18-CH3, 8-CH2CH3); com-
plex XII: 9.27 s (1H, H10), 9.04 s (1H, H5), 8.10 s
(1H, H20), 7.75 d.d [1H, 3-(CH=CH2), J 17.5 and
12.0 Hz], 6.02 d [1H, 3-(CH=CHHtrans), J 17.6 and
1.6 Hz], 5.98 br.d [1H, 3-(CH=CHHcis), J 11.6 Hz],
5.93 s (1H, H13(2)), 4.20 4.28 m (1H, H18), 1.44 d
(1H, H17, J 9.2 and 2.4 Hz), 3.70 s (3H, 132-CO2CH3),
3.59 s [3H, 17-(CH2CH2COOCH3)], 3.47 s (3H,
12-CH3), 3.13 s (3H, 2-CH3), 3.10 s (3H, 7-CH3),
3.54 3.65 m [2H, 8-(CH2CH3)], 2.06 2.42 m [4H,
17-(CH2CH2COOCH3)], 1.45 1.62 m (3H, 8-CH2
CH3); 1.44 d (3H, 18-CH3, J 7.2 Hz).
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2. Mironov, A.F., Itogi Nauki i Tekhniki. Sovremennye
problemy lazernoi fiziki (Results of Science and
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ture, Properties, Synthesis), Enikolopyan, N.S., Ed.,
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5. Belykh, D.V., Karmanova, L. P., Spirikhin, L. V., and
Kutchin, A.V., Mendeleev Commun., 2002, p. 77.
6. Tulaeva, L.A., Belykh, D.V., Yakovleva, N.M., Sel’-
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Vyssh. Uchebn. Zaved., Khim. Khim. Tekhnol., 2006,
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ACKNOWLEDGMENTS
The work was performed under the Program of
Support for Leading Scientific Schools of the
Presudent of the Russian Federation (project
no. NSh1206.2006.3).
7. Martynenko, L.I., Murav’eva, I.A., and Khalmurza-
ev, M.K., Stroenie, svoistva i primenenie -diketonatov
metallov (Structure, Properties and Application of
Metal -Diketonates), Moscow: Nauka, 1978, p. 35.
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