New porphyrin platinum conjugates for the cytostatic and photodynamic tumor therapy

Article abstract of DOI:10.1016/S0020-1693(02)01490-1

The combination of a porphyrin system and a platinum fragment in the same molecule should not only result in the additivity of the photodynamic activity of the porphyrin and the cytostatic activity of the platinum, but also in the enrichment of the porphyrin platinum conjugate in tumors, which platinum compounds alone do not show. New porphyrin platinum conjugates were obtained from the platinum complexes of a series of 1,2-diamines and hematoporphyrin or 13,17-bis(2-carboxyethyl)-3,8-bis[1-(ethyleneglycolmonoethylether)oxyethyl]-2,7, 12,18-tetramethylporphin. The 1,2-diamines were synthesized starting from the corresponding stilbenes via 1,2-diazides. The new platinum porphyrin conjugates showed promising antitumor activity in tests with the mammary carcinoma cell line MDA-MB-231.

Full text of DOI:10.1016/S0020-1693(02)01490-1

Inorganica Chimica Acta 350 (2003) 39ꢀ48
/
www.elsevier.com/locate/ica
New porphyrin platinum conjugates for the cytostatic and
photodynamic tumor therapy
H. Brunner *, K.-M. Schellerer
Institut fur Anorganische Chemie, Universitat Regensburg, D-93040 Regensburg, Germany
¨ ¨
Received 1 March 2002; accepted 3 April 2002
Dedicated in honor of Professor Pierre Braunstein
Abstract
The combination of a porphyrin system and a platinum fragment in the same molecule should not only result in the additivity of
the photodynamic activity of the porphyrin and the cytostatic activity of the platinum, but also in the enrichment of the porphyrin
platinum conjugate in tumors, which platinum compounds alone do not show. New porphyrin platinum conjugates were obtained
from the platinum complexes of a series of 1,2-diamines and hematoporphyrin or 13,17-bis(2-carboxyethyl)-3,8-bis[1-(ethylenegly-
colmonoethylether)oxyethyl]-2,7,12,18-tetramethylporphin. The 1,2-diamines were synthesized starting from the corresponding
stilbenes via 1,2-diazides. The new platinum porphyrin conjugates showed promising antitumor activity in tests with the mammary
carcinoma cell line MDA-MB-231.
# 2003 Elsevier Science B.V. All rights reserved.
Keywords: Porphyrin platinum conjugates; Cytostatic tumor therapy; Photodynamic tumor therapy; MDA-MB-231 cell line
1. Introduction
tissues [1,2], platinum complexes such as cisplatinum
and carboplatinum penetrate unselectively into all fast
growing tissues giving rise to the known side-effects
nausea, vomiting, myelosuppression and nephrotoxicity.
Thus, with porphyrin platinum conjugates a selective
enrichment of platinum compounds in tumors is ex-
pected. First papers in this direction have been pub-
Porphyrin platinum conjugates combine in the same
molecule platinum fragments and porphyrin systems
useful for two different approaches in cancer chemother-
apy, the ‘cytostatic therapy’ with platinum derivatives
and the ‘photodynamic therapy’ with porphyrin com-
pounds. Such porphyrin platinum conjugates should
show the cytostatic activity of the platinum part. On
irradiation, the photodynamic component of the por-
phyrin sensitizers should add. Furthermore, porphyrin
platinum conjugates should exceed mixtures of platinum
and porphyrin compounds with respect to tumor
selectivity. Whilst porphyrin derivatives enrich in cancer
lished [3ꢀ
9].
Antitumor active platinum compounds of the type
/
6] and have been submitted for publication [7ꢀ
/
L2PtX2 contain ligands L (non-leaving groups) and
ligands X (leaving groups). Typical leaving groups are
chloride or carboxylates. Within the cells they are
replaced first by water ligands and finally by DNA
nucleophiles (or biomolecules). Typical non-leaving
groups are ammonia or amines. Amine ligands should
contain NH groups to form hydrogen bonds [10,11],
primary amines being best. We published the synthesis
and antitumor activity of a series of porphyrin platinum
* Corresponding author. Tel.: ꢁ
4439.
E-mail address: henri.brunner@chemie.uni-regensburg.de (H.
Brunner).
/
49-941-943 4441; fax: ꢁ49-941-943
/
0020-1693/03/$ - see front matter # 2003 Elsevier Science B.V. All rights reserved.
doi:10.1016/S0020-1693(02)01490-1

40
H. Brunner, K.-M. Schellerer / Inorganica Chimica Acta 350 (2003) 39ꢀ48
/
conjugates in this journal, in which the non-leaving
groups of the platinum fragment were two ammonia
ligands [6]. In the present paper we extend these
investigations to a variety of 1,2-diaminoethane deriva-
tives as non-leaving groups [12].
3. The hydrochlorides of the diamines 10
/
13
ꢀ
The stilbenes 1, 2, 4 and 5 were transformed into the
hydrochlorides of the corresponding diamines 10ꢀ
/13 via
reduction of the diazides 6ꢀ9. The diazidation of the
/
double bond of the stilbenes was carried out with IN3,
generated in situ from ICl and NaN3 in acetonitrile. An
excess of NaN3 resulted in the substitution if Iꢂ by N3ꢂ
to give the diazides, which were successively reduced to
the corresponding diamines with LiAlH4 [18,19]. As a
chromatographic purification was unsuccessful, the
diamines were converted into the dihydrochlorides by
passing HCl through their methanol solution. Addition
of ether precipitated the dihydrochlorides. Compounds
The strategy is to synthesize suitable 1,2-diami-
noethane ligands and to prepare their PtCl2 complexes
(reaction with K2PtCl4). Next, the chloro ligands are
replaced by aqua ligands via reaction with AgNO3.
Then, the nitrate counter ions in the complex
[L2Pt(H2O)2](NO3)]2 are substituted by hydroxide ions
with a basic ion exchanger. Finally, the activated
complexes [L2Pt(H2O)2](OH)2 react with the porphyrin
ligands (in the form of carboxylic acids) to give the
porphyrin platinum conjugates [12].
10ꢀ/12 consisted of the cis- and trans-isomers, 13 was
the pure trans-product (Scheme 1).
4. The PtCl2 complexes 14
/
22
ꢀ
2. The stilbenes 1
/
5
ꢀ
For complexation of the diamines to the PtCl2
fragment, the corresponding diamine or its dihy-
drochloride (Scheme 1) was dissolved in water or a
mixture of water and tert-butanol. To the solution an
equimolar amount of K2PtCl4 was added and the pH
As intermediates for the synthesis of 1,2-diarylated
diaminoethanes the corresponding stilbenes were re-
quired. To prepare the stilbenes 1 and 2 the Wittig
olefination [13] was used. Benzyltriphenylphosphonium
chloride and 3-methoxybenzyltriphenylphosphonium
chloride were reacted with 3-methoxybenzaldehyde in
the presence of NaOEt to give 1 and 2 (Scheme 1).
The methyl group in the methyl ether 1 was split off
was brought to 5ꢀ
was formed and the dropping pH was successively
adjusted to pH 5ꢀ6 with 0.1 N NaOH. The reaction
was finished, when the pH no longer changed. With the
ligands 10ꢀ13, the PtCl2 complexes 14ꢀ17 were ob-
tained. In addition, 1,2-diaminoethane, 1,2-diamino-4-
chlorobenzylethane, 1,2-diamino-2-(4-methoxyben-
zyl)propane, trans-1,2-diaminocyclohexane and 2-ami-
nomethylpyridine were converted into the
corresponding PtCl2 complexes 18ꢀ22 (Scheme 2) [12].
/6. During the reaction a precipitate
/
with trimethylsilyliodide [14ꢀ16] in quinoline at 180 8C
to afford the phenol 3. Ethyleneglycolmonomethylether
was tosylated with tosylchloride and the tosylate was
/
/
/
used to etherify the OH group of 3 in tert-butanolꢀ
/
KOtBu to give 4 (Scheme 1).
4-Hydroxybenzaldehyde was reacted with (2-chloro-
/
ethyl)methylether in boiling DMFꢀ
ing 4-substituted benzaldehyde was submitted to a
McMurry synthesis with TiCl4ꢀZn in dioxane to give
the stilbene 5 [17] (Scheme 1).
/
K2CO3. The result-
Compounds 18 and 21 are well-known platinum com-
plexes in cancer therapy. Compound 19 has been
reported before [20]. The synthesis and characterization
of 20 and 22 will be described in the Section 8.
/
Scheme 1.

H. Brunner, K.-M. Schellerer / Inorganica Chimica Acta 350 (2003) 39ꢀ
/
48
41
indicarboxylic acids (ꢀ
1700 cmꢂ1) can be used to
check whether hydrolysis is complete. The complexation
of the porphyrindicarboxylates with the platinum frag-
/
ments results in a shift of the CO absorptions to ꢀ1600
/
cmꢂ1. Another diagnostic IR tool is the weak PtÃ
/
O
band around 375 cmꢂ1 in the dicarboxylato complexes.
The porphyrins exhibit the characteristic Soret band
at about 400 nm (molar extinction coefficient up to
400 000 l molꢂ1 cmꢂ1). The hematoporphyrin deriva-
tives show absorption spectra of the etio type, the
sequence of the satellite band intensity being IVꢁ
IIIꢁIIꢁI. The satellite band I appears at ꢀ620 nm,
II at ꢀ570 nm, III at ꢀ530 nm and IV at ꢀ500 nm.
/
/
/
/
/
/
/
As a consequence of the long wavelength absorption
maximum at 623 nm, common to all hematoporphyrin
derivatives, the penetration depth of the red light used
for the therapy is about 5 mm [22].
The magnetic anisotropy of the porphyrins expands
1
the H NMR spectra up to 15 ppm. The signals of the
four methine bridges of the hematoporphyrin deriva-
tives appear at about 10 ppm. The two NH protons
Scheme 2.
show a broad signal at about ꢂ4 ppm due to fast
/
5. The porphyrin platinum conjugates 23
/
31
ꢀ
exchange. The methyl groups of the hematoporphyrin
derivatives in the positions 2, 7, 12 and 18 are strongly
affected by the anisotropy and appear at 3.6 ppm. The
signals of the a-methylene groups in the positions 13 and
17 show up at 4.2 ppm and those of the b-methylene
groups at 3.2 ppm. The 1H NMR signals of the platinum
complexes tend to broaden.
All the diamine(porphyrinato-O,O?)platinum(II)
complexes were examined by mass spectrometry, mostly
with the LISIMS technique, embedded in a matrix
consisting of glycerol and DMSO. Interestingly, for
most of the porphyrin platinum compounds the mole-
cular ion was observed establishing their composition.
The last step in the synthesis of the porphyrin
platinum conjugates was the complexation of the
platinum fragments with the porphyrin ligands. For
this purpose it was necessary to transform the dichlor-
oplatinum(II) complexes into their reactive hydrolysis
products [21]. Compounds 14ꢀ22 were stirred with 2
/
mol equiv. of silver nitrate in aqueous solution under
exclusion of light for 1 week. Then the chloro ligands
had been replaced by aqua ligands and AgCl had
precipitated. Subsequently, the nitrate counter ions
were exchanged for hydroxide ions by chromatography
on a strongly basic ion exchanger. The activated
diamine(diaqua)platinum(II)-dihydroxides were reacted
with the porphyrin ligands hematoporphyrin and 13,17-
bis(2-carboxyethyl)-3,8-bis[1-(ethyleneglycolmonoethyl-
ether)oxyethyl]-2,7,12,18-tetramethylporphin, dissolved
in methanol, at room temperature for several hours. The
porphyrin platinum conjugates precipitated. For purifi-
cation the products were washed with water to remove
excess platinum compound and then with methanol to
remove unreacted ligand. Using this procedure, the
7. Cell tests
The complexes 23ꢀ31 were tested in three different
/
concentrations in DMF solution with the MDA-MB-
231 mammary carcinoma cell line with and without
irradiation as described in Ref. [23] and, in particular, in
Refs. [6ꢀ8]. The T/C values are listed in Table 1. The T/
/
porphyrin platinum conjugates 23ꢀ31 were obtained
/
C values express the relative inhibition of a compound
on the cell growth compared with the solvent reference.
The T/C values are defined by the equation:
(Schemes 3 and 4).
T ꢂ C0
T=C (%)ꢃ
× 100 (%)
6. Spectroscopy
C ꢂ C0
The course of the reactions described can be mon-
itored with IR spectroscopy. The porphyrins show the
characteristic, sharp NH absorption of pyrrole at 3300
cmꢂ1. The shift of the CO absorption of the esters
in which, T is the mean absorbance of the treated cells,
C the mean absorbance of the solvent control and C0
the mean absorbance of the cells at the time (tꢃ0),
/
when the drug was added. A T/C value of 100%
indicates a cell growth identical to the untreated control
(1740ꢀ
/
1725 cmꢂ1) during hydrolysis to the porphyr-

42
H. Brunner, K.-M. Schellerer / Inorganica Chimica Acta 350 (2003) 39ꢀ48
/
Scheme 3.
Scheme 4.

H. Brunner, K.-M. Schellerer / Inorganica Chimica Acta 350 (2003) 39ꢀ
/
48
43
Table 1
T/C values of the porphyrin platinum complexes 23ꢀ
mammary carcinoma cell line (solvent DMF)
/
31 measured at 1ꢄ
/
10ꢂ5, 5ꢄ
/
10ꢂ6, and 1ꢄ10ꢂ6 mol lꢂ1 in vitro on the MDA-MB-231
/
c (mmol lꢂ1
)
Without irradiation
1
With irradiation
1
5
10
5
10
23
24
95.49
100.39
102.19
91.69
112.49
105.39
95.69
119.89
88.49
93.79
91.59
135.09
/
6.1
8.9
9.8
6.9
9.2
9.6
6.9
7.4
8.6
7.8
5.0
8.9
74.79
80.89
73.79
87.99
60.49
66.99
69.19
99.69
34.79
76.29
46.19
115.89
/
4.7
10.5
8.3
11.0
5.2
8.3
7.7
7.8
7.7
6.9
9.2
9.9
61.29
54.19
58.99
84.39
33.29
38.49
34.19
67.69
6.29
51.49
24.59
85.69
/
3.3
82.69
91.89
81.29
63.29
118.89
92.99
102.19
92.59
74.99
49.09
87.39
98.59
/
10.5
36.39
39.19
31.99
47.59
27.59
40.89
48.09
37.19
2.49
21.09
41.39
44.39
/
6.2
8.1
7.4
6.4
4.4
6.6
7.4
8.7
1.4
3.1
7.0
8.6
19.79
14.79
24.59
37.69
1.39
14.99
4.19
12.59
10.99
18.79
29.19
30.99
/
6.2
4.8
5.8
5.3
6.6
4.9
3.2
6.7
3.1
1.9
3.3
6.4
/
/
/
8.7
4.9
7.3
6.9
7.9
4.9
5.4
4.0
5.4
4.4
8.4
/8.3
/
/
25
/
/
/
/6.6
/
/
26
/
/
/
/8.5
/
/
27
/
/
/
/9.9
/
/
28
/
/
/
/16.1
/
/
29
/
/
/
/9.2
/
/
29L a
30
/
/
/
/10.1
/
/
/
/
ꢂ/
/
/7.5
/
ꢂ/
/
31
/
/
/
/5.4
/
/
Cisplatinum
/
/
/
/6.1
/
/
Photofrin
/
/
/
/10.6
/
/
a
L abbreviates liposome formulation.
containing only the solvent. A T/C value of 0% means
that cell proliferation has come to a complete stop.
8. Experimental
IR: Beckman spectrometer 4240, Perkinꢀ
/
Elmer-FT-
To classify the T/C values of the complexes 23ꢀ31,
/
1
IR spectrometer Paragon 1000 PC. H NMR: Bruker
WM 250 (250 MHz) and ARX 400 (400 MHz);
tetramethylsilane as internal standard. MS: Finnigan
the clinically used compounds cisplatinum and Photo-
frin were included in the tests. The T/C values show that
cisplatinum lacks phototoxicity and Photofrin has no
cytotstatic activity. The values indicate that the por-
MAT 95 and MAT 112S. Mp: Buchi SMP 20. UVꢀVis:
/
¨
Kontron Instruments spectrophotometer UVIKON 930
and UVIKON 922.
phyrin platinum conjugates 23ꢀ31, in particular com-
/
pounds 30, 27 and 29, are as active or even more active
than cisplatinum and Photofrin, demonstrating the
validity of our approach.
Hemin (Fluka) was used without further purification.
Protoporphyrindimethylester was synthesized according
to Ref. [28].
The nomenclature of the porphyrins and their com-
plexes was based on the recommendation of IUPAC and
the International Union of Biochemistry (IUB) [29]. In
the enumeration the derivatized groups were defined as
3 and 8. This led to the numbers 13 and 17 for the
propionic acid groups.
1,2-Diamino-2-(4-methoxybenzyl)propane was ob-
tained from 4-methoxyphenylacetone in a Strecker
synthesis with NaCN and ammonia and a successive
reduction with LiAlH4. 2-Aminomethylpyridine was
prepared by LiAlH4 reduction of commercial 2-cyano-
pyridine.
As complexes of the type 23ꢀ31 were insoluble in
/
water they had to be applied in solvents such as DMF,
which were miscible with water. For a pharmaceutical
application, water solubility would be much better.
Embedding of water-insoluble compounds into lipo-
somes is a possibility to make them water-soluble [24ꢀ
/
26]. Compound 29 was embedded in the lipid
L-a-
dioleylphosphatidylcholin in aqueous solution [27]. For
the embedding procedure, the determination of the
concentration of the solutions and the time-stability of
the formulations see Ref. [12]. The T/C values in line
29L of Table 1 show that complex 29 maintained its
cytotostatic and photodynamic activity in a liposome
formulation allowing an application in water.
8.1. 3-Methoxybenzyltriphenylphosphonium chloride
Complex 29 was also tested with the HaCat cell line in
DMF solutions as well as in liposome formulations in
water [12]. The activity was strongly concentration-
dependent. The vitality of the cells was almost un-
changed at a concentration of 1 mmol lꢂ1 and reached a
maximum at 5 mmol lꢂ1. At higher doses toxic effects
showed up both for DMF solutions and liposome
formulations.
3-Methoxybenzylchloride (26.0 g, 166 mmol) and
triphenylphosphane (43.5 g, 166 mmol) were heated to
80 8C for 25 min. A white precipitate was formed. The
mixture was suspended in 250 ml of Et2O. The
precipitate was washed with Et2O and dried. Yield:
18.2 g (27%). White, hygroscopic solid. C26H24ClOP
(418.91). IR (film): n 3080, 3060, 3000, 2870, 2800 cmꢂ1
.

44
H. Brunner, K.-M. Schellerer / Inorganica Chimica Acta 350 (2003) 39ꢀ48
/
1H NMR (CDCl3): d 8.35ꢀ
2H, CH2), 3.75 (s, 2H, OCH3).
The same procedure was used to prepare benzyltri-
phenylphosphonium chloride.
/
7.48 (m, 19H, Har), 5.35 (s,
3010, 2960, 2900, 2830 cmꢂ1
7.53ꢀ6.99 (m, 9H, Har), 6.73 (m, 2H, CH), 4.76 (s, 1H,
CH).
.
1H NMR (CDCl3): d
/
8.2. cis/trans-1-(3-Methoxyphenyl)-2-phenylethene (1)
8.5. 2-Methoxyethyl-4-toluenesulfonate
Na (9.2 g, 0.4 mol) was dissolved in abs. EtOH (100
ml) under N2. Benzyltriphenylphosphonium chloride
(16.8 g, 40 mmol) was added in portions leading to a
yellow suspension. A solution of 3-methoxybenzalde-
hyde (5.44 g, 40 mmol) in EtOH (10 ml) was added.
After 4 h stirring at room temperature (r.t.) H2O (50 ml)
was added and the mixture was extracted with CH2Cl2.
The organic phase was dried over MgSO4, the solvent
was removed and the residue was suspended in PE 40/60
(200 ml). For further purification it was chromato-
2-Methoxyethanol (7.61 g, 100 mmol) was dissolved
in a mixture of CH2Cl2 (100 ml) and pyridine (20 ml) at
0 8C. 4-Toluenesulfonylchloride (21.0 g, 110 mmol) was
added. After stirring at r.t. for 20 h, 10 g of ice were
added. After 1 h stirring the mixture was washed with
cold H2SO4 and 50 ml of H2O. The organic phase was
filtered over SiO2 (20ꢄ5 cm) with CH2Cl2, dried and
/
evaporated. Distillation at 130 8C in high vacuum.
Yield: 15.0 g (65%). Colorless liquid. C10H14O4S
1
3
(230.28). H NMR (CDCl3): d 7.80, 7.30 (2d, Jꢃ8.1
/
graphed over SiO2 (15ꢄ
/
3 cm) using PE (40/60) as
Hz, 4H, C6H4), 4.20, 3.65 (2m, 4H, OCH2CH2O), 3.30
(s, 3H, OCH3), 2.40 (s, 3H, CH3).
eluent. First, the product was obtained as a cis/trans
isomer mixture. Yield: 6.51 g (77%). Colorless oil. Anal.
Calc. for C15H14O (210.28): C, 85.67; H, 6.71. Found: C,
85.37; H, 6.86%. IR (film): n 3060, 3040, 3010, 2935,
2920, 2810 cmꢂ1. H NMR (CDCl3): d 7.56ꢀ
9H, Har), 6.74 (m, 2H, CH), 3.73 (s, 3H, OCH3).
8.6. cis/trans-[3-(2-
Methoxyethoxy)phenyl]phenylethene (4)
1
/6.96 (m,
Kalium-tert-butylate (309 mg, 2.75 mmol) was dis-
solved in tert-BuOH (50 ml) and a solution of 3 (500
mg, 2.27 mmol) in tert-BuOH (5 ml) was added. After
stirring the yellow reaction mixture for 15 min, 2-
methoxyethyl-4-toluenesulfonate (583 mg, 2.27 mmol),
dissolved in 5 ml of tert-BuOH, was added and stirred
for 24 h at r.t. After removal of the solvent the residue
8.3. cis/trans-1,2-Bis(3-methoxyphenyl)ethene (2)
3-Methoxybenzyltriphenylphosphonium
chloride
(18.2 g, 43 mmol) was reacted with 3-methoxybenzalde-
hyde (5.92 g, 43 mmol) and the tenfold amount of Na.
After 65 h at r.t. the solution was hydrolyzed and
extracted with CH2Cl2 (2ꢄ/100 ml). The dark yellow
was chromatographed over SiO2 (20ꢄ/3 cm) with PE
organic phase was dried over MgSO4 and the solvent
was removed. The oily product was stirred with PE (40/
60, 200 ml) for 20 h at r.t. After filtration and removal of
the solvent an oil was obtained containing a mixture of
the cis/trans isomers. Yield: 5.63 g (54%). Yellow oil.
(40/60)ꢀEt2O 5:1. Yield: 400 mg (69%). White solid
/
(melting point (m.p.) 221 8C). C17H18O2 (254.31). IR
1
(KBr): n 3050, 3015, 2970, 2915, 2870, 2810 cmꢂ1. H
NMR (CDCl3): d 7.53ꢀ
5.4 Hz, 2H, CH), 4.16, 3.77 (2d, Jꢃ
OCH2CH2O), 3.94, 3.66 (2d, 3Jꢃ
7.3 Hz, 4H, trans-
/
6.75 (m, 9H, Har), 6.57 (d, 3Jꢃ
/
3
/
7.3 Hz, 4H, cis-
C16H16O2 (240.29). IR (film): n 3050, 3010, 2960, 2940,
2830 cmꢂ1. H NMR (CDCl3): d 7.23ꢀ
Har), 6.66 (m, 2H, CH), 3.82 (s, 6H, OCH3).
/
1
/6.81 (m, 8H,
OCH2CH2O), 3.47, 3.41 (2s, 6H, cis- and trans-OCH3).
8.4. cis/trans-1-(3-Hydroxyphenyl)-2-phenylethene (3)
8.7. 4-(2-Methoxyethoxy)benzaldehyde
Compound 1 (1.50 g, 7.13 mmol) was dissolved in 10
ml of quinoline. After addition of trimethylsilyliodide
(2.14 g, 10.7 mmol) the mixture was heated to 180 8C for
70 min. The reaction mixture was hydrolyzed at 0 8C
4-Hydroxybenzaldehyde (3.00 g, 24.6 mmol) was
heated together with K2CO3 (12.0 g, 86.8 mmol) and
(2-chloroethyl)methylether (6.99 g, 73.8 mmol) in abs.
DMF (60 ml) under N2. After 44 h the reaction was
quantitative (DC control). After removal of the solvent
with 5% HCl (50 ml) and extracted with Et2O (3ꢄ50
/
ml). After removal of the solvent the oily residue was
stirred with 10% methanolic NaOH (50 ml) for 20 h at
r.t. After removal of the solvent the residue was
the mixture was filtered over SiO2 (15ꢄ5 cm) with Et2O
/
to remove excess K2CO3. The resulting yellow liquid
was distilled. Yield: 3.10 g (70%). Nearly colorless oil.
Anal. Calc. for C10H12O3 (180.20): C, 66.65; H, 6.71.
Found: C, 66.42; H, 6.65%. IR (KBr): n 3070, 2980,
chromatographed (SiO2, 20ꢄ3 cm) with Et2O/PE (40/
/
60) 1:1. Recrystallisation from 120 ml of boiling PE (40/
60). Yield: 460 mg (33%). Colorless crystals (m.p.
194 8C). Anal. Calc. for C14H12O (196.25): C, 85.68;
H, 6.16. Found: C, 85.42; H, 6.09%. IR (KBr): n 3540,
2930, 2880, 2820, 1690 cmꢂ1. 1H NMR (CDCl3): d 9.88
3
(s, 1H, CHO), 7.83, 7.03 (2d, Jꢃ
/
6.8 Hz, 4H, C6H4),
4.20, 3.77 (2m, 4H, OCH2CH2O), 3.46 (s, 3H, OCH3).

H. Brunner, K.-M. Schellerer / Inorganica Chimica Acta 350 (2003) 39ꢀ
/
48
45
8.8. trans-1,2-Bis[4-(2-methoxyethoxy)phenyl]ethene
(5)
8.10.1. 1,2-Diamino-1-(3-methoxyphenyl)-2-
phenylethane-dihydrochloride (10)
Yield: 560 mg (28%). White, hygroscopic solid.
C15H20Cl2N2O (315.21). IR (KBr): n 3430, 2990, 2900,
4-(2-Methoxyethoxy)benzaldehyde (500 mg, 2.77
mmol) was dissolved in absolute dioxane (70 ml). At
1
2850 cmꢂ1. H NMR (CDCl3): d 7.81ꢀ
/
6.86 (m, 9H,
ꢂ
/
5 8C TiCl4 (788 mg, 4.16 mmol) was added dropwise,
resulting in a yellow suspension. Zn powder (540 mg,
8.31 mmol) (B60 mm, Fa. Merck) was added with
Har), 3.91, 3.74 (2s, 3H, D,L- and meso-OCH3).
/
cooling. The brown reaction mixture was boiled for 20
h. The black solution was poured onto ice water (200
ml). The organic phase was washed three times with
Et2O (250 ml), dried over Na2SO4 and reduced to 30 ml.
The product crystallized at r.t. within 48 h. Yield: 360
mg (80%). White plates (m.p. 180 8C). Anal. Calc. for
C20H24O4 (328.41): C, 73.14; H, 7.36. Found: C, 73.30;
H, 7.23%. IR (KBr): n 2940, 2900, 2890, 2840, 2770
8.10.2. 1,2-Diamino-1,2-bis(3-methoxyphenyl)ethane-
dihydrochloride (11)
Yield: 365 mg (16%). White, hygroscopic solid (m.p.
227 8C). C16H22Cl2N2O2 (345.24). IR (KBr): n 3440,
1
2930, 2890, 2850 cmꢂ1. H NMR (CD3OD): d 9.21,
8.90 (2s, 6H, NH3), 7.49ꢀ6.85 (m, 8H, Har), 3.81, 3.68
/
(2s, 3H, D,L- and meso-OCH3).
cmꢂ1. 1H NMR (CDCl3): d 7.40, 6.90 (2d, 3Jꢃ
8.4 Hz,
/
8H, C6H4), 6.92 (s, 2H, CH), 4.13, 3.76 (2m, 4H,
OCH2CH2O), 3.46 (s, 6H, OCH3). MS (EI, 70 eV): m/
8.10.3. 1,2-Diamino-1-[3-(2-methoxyethoxy)phenyl]-2-
phenylethane-dihydrochloride (12)
z 328 (100, M), 270 (9, Mꢂ
/
CH2CHOCH3), 212 (22,
Yield: 175 mg (8%). White, hygroscopic solid. Anal.
Calc. for C17H24Cl2N2O2 (359.07): C, 56.87; H, 6.74; N,
7.80. Found: C, 56.79; H, 6.55; N, 7.81%. IR (KBr): n
Mꢂ2ꢄ(CH2CHOCH3)).
/
/
3440, 3060, 3025, 2910, 2875, 2820 cmꢂ1
.
1H NMR
6.81 (m,
9H, Har), 5.00, 4.85 (int. 2), 4.13, 4.00 (int. 2), 3.67, 3.61
(DMSO-d6): d 9.16, 8.89 (2s, 6H, NH3), 7.74ꢀ
/
8.9. The diazides 6ꢀ9
/
(6m, 4H, D,L- and meso-OCH2), 3.32, 3.29 (2s, 3H, D,L
and meso-OCH3).
-
Under N2 protection ICl (2.40 g, 15 mmol) in 1.5 ml
of CH3CN was added to NaN3 (1.95 g, 30 mmol) in 50
ml of CH3CN. The yellow suspension was cooled to
ꢂ10 8C and the solution of 0.7 mmol of the stilbene 1, 2,
/
8.10.4. 1,2-Diamino-1,2-bis[4-(2-
methoxyethoxy)phenyl]ethane-dihydrochloride (13)
Due to the limited solubility in ether, 9 was reduced
with LiAlH4 in THF. Yield: 2.20 g (31%). Hygroscopic,
4 and 5, respectively, in 5 ml of CH3CN was added
dropwise. After 1.5 h the mixture was brought to r.t. and
then refluxed for 1 h. 150 ml of H2O was added.
Extraction with 150 ml of ether (3ꢄ
phase, which was washed with 50 ml of H2O (4ꢄ
dried with MgSO4. Removal of the solvent afforded the
diazides 6ꢀ9 in 93ꢀ96% yield as brown oils. Their IR
spectra showed the ÃN3 band at 2090ꢀ
2100 cmꢂ1
/
) gave an organic
brown solid. C20H30Cl2N2O4 (433.34). IR (KBr): n 3420,
2920, 2880, 2830 cmꢂ1. H NMR (CD3OD): d 7.71ꢀ
/) and
1
/
6.94(m, 8H, C6H4), 4.21, 4.10, 3.75 (3m, 8H, OCH2),
3.43, 3.40 (2s, 6H, OCH3).
/
/
/
/
(film). Purification was avoided because of the danger
of explosion.
8.11. The diamine(dichloro)platinum(II) complexes
(14ꢀ22)
/
8.10. The diamine-dihydrochlorides 10ꢀ
/
13
Diamine-dihydrochlorides (10ꢀ
diamines 1,2-diaminoethane, 1,2-diamino-4-chloroben-
zylethane, 1,2-diamino-2-(4-methoxybenzyl)propane,
trans-1,2-diaminocyclohexane, 2-aminomethylpyridine,
respectively, were dissolved in H2O or a mixture of
water and tert-BuOH and the pH was brought to 6. An
aqueous solution of K2PtCl4 (125 mg, 0.30 mmol) was
added. The complexation took place at r.t. or in a bath
of maximal 40 8C. During the reaction a yellow pre-
cipitate was formed and the pH dropped. With 0.1 N
/
13) (0.30 mmol) or the
Under N2 protection LiAlH4 (1.35 g, 35.7 mmol) was
suspended in 50 ml of ether. Diazide 6ꢀ9 of (6.46
/
mmol), respectively, dissolved in 50 ml of ether, was
added dropwise at 0 8C. After 30 min stirring at 0 8C the
reaction mixture was refluxed for 1 h and hydrolyzed
with 10 ml of H2O. The residue was washed with ether
and the organic phase was dried with MgSO4. Removal
of the solvent gave the diamine as a yellow oil. The oil
was dissolved in 20 ml of methanol. At 0 8C dry HCl
was passed through the methanol solution. 200 ml of
ether was added to the yellow solution affording the
NaOH it was successively adjusted to pH 5ꢀ6. The
/
reaction was finished, when the pH no longer changed.
The precipitate was filtered, washed with water and
ethanol and dried.
diamine-dihydrochlorides 10ꢀ13 as white precipitates.
/

46
H. Brunner, K.-M. Schellerer / Inorganica Chimica Acta 350 (2003) 39ꢀ48
/
8.11.1. [1,2-Diamino-1-(3-methoxyphenyl-2-
phenylethane](dichloro)platinum(II) (14)
Diamine-dihydrochloride (10), solvent water, reaction
3210, 3100, 3020, 2960, 2920, 2830, 1605, 1575, 1550, 320
cmꢂ1. 1H NMR (DMF-d7): d 7.32, 6.93 (2d, 3Jꢃ
8.6 Hz,
4H, C6H4), 5.92, 4.92 (2s, 4H, NH2), 3.80 (s, 3H, OCH3),
/
2
time 4 h. Yield: 120 mg (74%). Yellow powder (m.p.ꢁ
/
3.17, 3.05 (2d, Jꢃ13.2 Hz, 2H, CH2), 2.54 (m, 2H,
/
250 8C). Anal. Calc. for C15H18Cl2N2OPt (508.29): C,
35.44; H, 3.57; N, 5.51. Found: C, 35.87; H, 3.27; N,
5.51%. IR (KBr): n 3260, 3220, 3040, 2980, 2900, 2830,
CH2NH2), 1.37 (s, 3H, CH3).
8.11.6. 2-Aminomethylpyridine(dichloro)platinum(II)
(22)
2-Aminomethylpyridine, solvent water, reaction time
1605, 1575, 1550, 320 cmꢂ1
.
8.11.2. [1,2-Diamino-1,2-bis(3-
methoxyphenyl)ethane](dichloro)platinum(II) (15)
Diamine-dihydrochloride (11), solvent water, reaction
6 h. Yield: 75 mg (62%). Yellow powder (m.p.ꢁ250 8C).
/
Anal. Calc. for C6H8Cl2N2Pt (374.12): C, 19.26; H, 2.16;
N, 7.48. Found: C, 19.27; H, 2.39; N, 7.28%. IR (KBr):
1
time 6 h. Yield: 125 mg (64%). Yellow powder (m.p.ꢁ
/
n 3220, 3190, 3120, 2950, 2925, 1605, 320 cmꢂ1. H
NMR (DMF-d7): d 9.25 (m, 1H, H-6), 8.19 (m, 1H, H-
250 8C). Anal. Calc. for C16H20Cl2N2O2Pt (538.32): C,
35.70; H, 3.74; N, 5.20. Found: C, 35.78; H, 3.72; N,
5.38%. IR (KBr): n 3250, 3210, 3170, 3000, 2960, 2940,
4), 7.73 (m, 1H, H-3), 7.54 (m, 1H, H-5), 6.24 (s, 2H,
3
NH2), 4.37 (t, Jꢃ/6.0 Hz, 2H, CH2).
2830, 1605, 320 cmꢂ1. 1H NMR (DMF-d7): d 7.37ꢀ
6.75
/
(m, 8H, Har), 6.17, 5.64 (2s, 4H, NH2), 3.67 (s, 6H,
OCH3).
8.12. The diamine(porphyrinato-O,O?)platinum(II)
complexes (23ꢀ31)
/
8.11.3. {1,2-Diamino-1-[3-(2-methoxyethoxy)phenyl]-
2-phenylethane}(dichloro)platinum(II) (16)
Diamine-dihydrochloride (12), solvent water. The
precipitate which formed within 1 h was discarded.
The reaction was accelerated by heating to 40 8C for 3 h.
Diamine(dichloro)platinum(II) complex (14ꢀ20) (0.20
/
mmol), respectively, was suspended in 30 ml of H2O by
stirring and ultrasound sonification. AgNO3 (68 mg,
0.40 mmol) was added and the reaction mixture was
stirred at r.t. for 7 days in the dark. The precipitated
AgCl was filtered off. The filtrate was brought on top of
25 g of a strongly basic ion exchanger (Fa. Merck,
Ionenaustauscher III) which had been activated with
100 ml of 2 N NaOH and eluted with H2O to pH 9. The
solution leaving the ion exchanger dropped into the
solution of 0.20 mmol of the porphyrin ligand (hema-
toporphyrin or 13,17-bis(2-carboxyethyl)-3,8-bis[1-
(ethyleneglycolmonoethylether)oxyethyl]-2,7,12,18-tet-
ramethylporphin), dissolved in methanol. After stirring
at r.t. for 20 h, the precipitate was isolated by filtration,
washed with water and methanol and dried.
Yield: 95 mg (32%). Yellow powder (m.p.ꢁ250 8C).
/
Anal. Calc. for C17H22Cl2N2O2Pt (552.34): C, 36.96; H,
4.01; N, 5.07. Found: C, 36.56; H, 4.11; N, 4.97%. IR
(KBr): n 3190, 3090, 2920, 2870, 1590, 1575, 325 cmꢂ1
.
1H NMR (DMF-d7): d 7.59ꢀ
6.72 (m, 11H, Har, CH),
6.33, 5.67 (2s, 4H, NH2), 4.13, 3.66 (2m, 4H, OCH2),
3.33 (s, 3H, OCH3).
/
8.11.4. {1,2-Diamino-1,2-bis[4-(2-
methoxyethoxy)phenyl]ethane}(dichloro)platinum(II)
(17)
Diamine-dihydrochloride (13), solvent 40 ml of water
and 6 ml of tert-BuOH. The reaction was accelerated by
heating to 40 8C for 3 h. Yield: 65 mg (31%). Yellow
8.12.1. [1,2-Diamino-1-(3-methoxyphenyl)-2-
phenylethane-N,N?][13,17-bis(2-carboxylatoethyl)-3,8-
bis(1-hydroxyethyl)-2,7,12,18-tetramethylporphin-
O,O?]platinum(II) (23)
powder
C20H28Cl2N2O4Pt (626.42): C, 38.34; H, 4.51; N, 4.47.
(m.p.ꢁ
/
250 8C).
Anal.
Calc.
for
Found: C, 38.39; H, 4.76; N, 4.30%. IR (KBr): n 3180,
3090, 2960, 2910, 2865, 2800, 1600, 320 cmꢂ1. 1H NMR
Pt complex 14, ligand hematoporphyrin in 50 ml of
MeOH. Yield: 140 mg (70%). Redꢀ
/
brown solid (m.p.ꢁ
/
3
(DMF-d7): d 7.80, 6.82 (2d, Jꢃ/8.6 Hz, 8H, C6H4),
250 8C). C49H54N6O7Pt (1034.09). IR (KBr): n 3400,
3305, 3210, 3140, 2980, 2930, 2840, 1610, 1370, 370
6.57, 5.98, 5.53, 3.70 (4s, 4H, NH2), 4.06, 3.64 (2m, 8H,
OCH2), 3.51 (s, 3H, OCH3), 2.91, 2.74 (2m, 2H,
CHNH2). 195Pt NMR (DMF-d7, 86 MHz, Na2PtCl6
cmꢂ1. PI-LISIMS (glycerolꢀ
/DMSO): 1032 (10, MH),
599 (100, LigH). UVꢀ/Vis (DMSO): l (nm) (log o) 407
ext.): d ꢂ
/
2266 (m).
(5.05), 505 (4.13), 535 (3.91), 570 (3.86), 623 (3.48).
8.11.5. [D,L-1,2-Diamino-2-(4-
methoxybenzyl)propane](dichloro)platinum(II) (20)
8.12.2. [1,2-Diamino-1,2-bis(3-methoxyphenyl)ethane-
N,N?]{13,17-bis(2-carboxylatoethyl)-3,8-bis[1-
(ethyleneglycolylmonoethylether)oxyethyl]-2,7,12,18-
tetra-methylporphin-O,O?}platinum(II) (24)
1,2-Diamino-2-(4-methoxybenzyl)propane,
water, reaction time 5 h. Yield: 217 mg (78%). Yellow
solvent
powder
C11H18Cl2N2O2Pt (460.25): C, 28.70; H, 3.94; N, 6.08.
Found: C, 28.68; H, 3.89; N, 6.12%. IR (KBr): n 3260,
(m.p.ꢁ
/
250 8C).
Anal.
Calc.
for
Pt complex 15, ligand 13,17-bis(2-carboxyethyl)-3,
8-bis[1-(ethyleneglycolmonoethylether)oxyethyl]-
2,7,12,18-tetramethylporphin in 50 ml of MeOH. Yield:

H. Brunner, K.-M. Schellerer / Inorganica Chimica Acta 350 (2003) 39ꢀ
/
48
47
120 mg (51%). Redꢀ
/
brown solid (m.p.ꢁ
/
250 8C). Anal.
(log o): 401 (4.35), 501 (3.35), 535 (3.12), 572 (3.08),
621 (2.81).
Calc. for C58H72N6O10Pt (1208.25): C, 57.65; H, 6.01;
N, 6.95. Found: C, 57.72; H, 6.22; N, 7.02%. IR (KBr):
n 3300, 3200, 3130, 2960, 2910, 2850, 1590, 1370, 375
cmꢂ1. 1H NMR (DMF-d7): d 10.78, 10.73, 10.56, 10.35
8.12.6. [1,2-Diamino-1-(4-chlorobenzyl)ethane-
N,N?][13,17-bis(2-carboxylatoethyl)-3,8-bis(1-
hydroxyethyl)-2,7,12,18-tetramethylporphin-
O,O?]platinum(II) (28)
(4s, 4H, CH), 7.06ꢀ
4.47 (m, 4H, CCH2), 4.00ꢀ
CCH3, CH2CO2, OCH3, CCH3), 2.23 (d, Jꢃ
6H, CHCH3), 1.07 (m, 6H, CH2CH3), ꢂ3.66 (s, 2H,
NH). 195Pt NMR (DMF-d7, 86 MHz, Na2PtCl6 ext.): d
1811 (m). UVꢀVis (DMSO): l (nm) (log o) 402 (5.30),
/6.19 (m, 14H, C6H4, NH2, CHCH3),
/
2.94 (m, 34H, OCH2, OCH3,
3
/6.5 Hz,
Platinum complex 19, ligand hematoporphyrin in 25
/
ml of MeOH. Yield: 75 mg (36%). Brown solid (m.p.ꢁ
/
250 8C). Anal. Calc. for C43H49ClN6O6Pt×
/2H2O
ꢂ
/
/
(1012.37): C, 51.02; H, 5.27; N, 8.30. Found: C, 51.20;
H 5.00; N, 7.91%. IR (KBr): n 3420, 3310, 3230, 2970,
499 (4.39), 534 (4.26), 568 (4.21), 621 (4.09).
2920, 2860, 1610, 1375, 375 cmꢂ1. UVꢀ
Vis (DMSO): l
(nm) (log o) 401 (5.16), 499 (4.32), 534 (4.21), 568 (4.16),
621 (4.07).
/
8.12.3. {1,2-Diamino-1-[3-(2-methoxyethoxy)phenyl]-
2-phenylethane-N,N?}{13,17-bis(2-carboxylatoethyl)-
3,8-bis[1-(ethyleneglycolylmonoethylether)oxyethyl]-
2,7,12,18-tetramethylporphin-O,O?}platinum(II) (25)
Pt complex 16, ligand 13,17-bis(2-carboxyethyl)-3,
8-bis[1-(ethylenegylcolmonoethylether)oxyethyl]-
2,7,12,18-tetramethylporphin in 40 ml of MeOH. Yield:
8.12.7. [1,2-Diamino-2-(4-methoxybenzyl)propane-
N,N?]{13,17-bis(2-carboxylatoethyl)-3,8-
bis(ethylen-eglycolmonoethylether)oxyethyl]-2,7,12,18-
tetramethyl-porphin-O,O?}platinum(II) (29)
Pt complex 20, ligand 13,17-bis(2-carboxyethyl)-3,8-
bis[1-(ethylenegylcolmonoethylether)oxyethyl]-
2,7,12,18-tetramethylporphin in 30 ml of MeOH. Yield:
40 mg (17%). Brown solid (m.p. ꢁ 250 8C).
C59H74N6O10Pt (1222.36). IR (KBr): n 3300, 3220,
3110, 2970, 2900, 2840, 1590, 1370, 370 cmꢂ1. PI-
/
155 mg (33%). Redꢀ
C53H70N6O9Pt (1130.18). IR (KBr): n 3300, 3220,
3100, 2980, 2930, 1620, 1370, 370 cmꢂ1 1H NMR
(DMF-d7): d 10.72, 10.71, 10.66, 10.62 (4s, 4H, CH),
/
brown solid (m.p.ꢁ
/
250 8C).
LISIMS (glycerol ꢀ
/
DMSO): m /z 1301 (80, Mꢁ
/
DMSOꢁH), 1223 (80, MH), 743 (100, LigH). UVꢀ
/
/
.
Vis (DMSO): l (nm) (log o) 403 (5.19), 502 (4.14), 536
(3.95), 571 (3.86), 622 (3.49). Fluorescence (DMSO): l
(nm) (rel. units) 514 (135.7), 627 (21.4).
3
7.10, 6.86 (2d, Jꢃ
CHCH3), 4.33 (m, 4H, CCH2), 3.75 (s, 3H, OCH3),
3.70, 3.68, 3.61, 3.55 (4s, 12H, CCH3), 3.51ꢀ3.21 (m,
12H, OCH2), 3.03 (m, 4H, CH2CO2), 2.17 (m, 6H,
/
8.1 Hz, 4H, C6H4), 6.26 (m, 2H,
/
8.12.4. {1,2-Diamino-1,2-bis[4-(2-methoxyethoxy)
phenyl]ethane-N,N?}{13,17-bis(2-carboxylatoethyl)-
3,8-bis[1-(ethyleneglycolmonoethylether)oxyethyl]-
2,7,12,18-tetramethylporphin-O,O?}platinum(II) (26)
Platinum complex 17, ligand 13,17-bis(2-carboxy-
ethyl)-3,8-bis[1-(ethyleneglycolmonoethylether)ox-
y-ethyl]-2,7,12,18-tetramethylporphin in 30 ml of
3
CHCH3), 1.22 (s, 3H, CH3), 1.04 (t, Jꢃ
CH2CH3), ꢂ3.85 (s, 2H, NH). PI-LISIMS (glycerolꢀ
DMSO): m /z 1130 (10, M H), 1041 (7, Mꢂ
OCH2CH2OCH2CH3ꢁH), 743 (100, LigH), 670 (30,
Lig à CH2 CH2 OCH2 CH3 ꢁH), 654 (50, Lig Ã
OCH2CH2OCH2CH3ꢁH). UVꢀVis (DMSO): l (nm)
/6.7 Hz, 6H,
/
/
/
/
/
/
/
/
/
MeOH. Yield: 25 mg (10%). Brown solid (m.p. ꢁ
/
(log o) 408 (5.10), 503 (4.08), 532 (3.88), 568 (3.83), 622
(3.46).
250 8C). C60H82N6O12Pt (1274.35). IR (KBr): n 3290,
3220, 3180, 2940, 2905, 2830, 1595, 1365, 370 cmꢂ1. PI-
LISIMS (glycerol ꢀ
/
DMSO): m /z 1351 (30, Mꢁ
/
8.12.8. [trans-1,2-Diaminocyclohexane-N,N?]{13,17-
bis(2-carboxylatoethyl)-3,8-bis[1-
(ethyleneglycolylmonoethylether)oxyethyl]-2,7,12,18-
DMSOꢁH), 1273 (40, MH), 743 (100, LigH). UVꢀ
/
/
Vis (DMSO): l (nm) (log o) 407 (4.84), 507 (3.71), 543
(3.62), 571 (3.51), 638 (3.30).
tetramethylporphin-O,O?}platinum(II) (30)
Platinum complex 21, ligand 13,17-bis(2-carbox-
yethyl)-3,8-bis[1-(ethyleneglycolmonoethylether)ox-
yethyl]-2,7,12,18-tetramethylporphin in 50 ml of MeOH.
8.12.5. (1,2-Diaminoethane-N,N?)[13,17-bis(2-
carboxylatoethyl)-3,8-bis(1-hydroxyethyl)-2,7,12,18-
tetramethylporphin-O,O?]platinum(II) (27)
Yield: 125 mg (60%). Brown solid (m.p.ꢁ250 8C). Anal.
/
Pt complex 18, ligand deuteroporphyrin in 30 ml of
EtOH and 40 ml of THF. Yield: 85 mg (59%). Brown
Calc. for C48H66N6O8Pt (1050.10): C, 54.90; H, 6.34; N,
8.00. Found: C, 55.45; H, 6.63; N, 7.56%. IR (KBr): n
3300, 3205, 3080, 2960, 2910, 2850, 1600, 1360, 375
cmꢂ1. 1H NMR (DMF-d7): d 10.84, 10.73, 10.69, 10.34
(4s, 4H, CH), 6.36 (m, 2H, CHCH3), 4.39 (m, 4H,
CCH2), 4.01 (m, 2H, CH2CHNH2), 3.80, 3.77, 3.70, 3.68
solid (m.p.ꢁ250 8C). Anal. Calc. for C30H36N6O4Pt
/
(739.68): C, 48.71; H, 4.91; N, 11.36. Found: C, 48.32;
H, 5.01; N, 10.51%. IR (KBr): n 3300, 3200, 2950, 2900,
2835, 1600, 1365, 370 cmꢂ1. PI-LISIMS (glycerolꢀ
/
DMSO): m/z 817 (45, Mꢁ
/
DMSOꢁ
Vis (DMSO): l (nm)
/
H), 739 (50,
(4s, 12H, CCH3), 3.62ꢀ3.36 (m, 12H, OCH2), 3.15 (m,
/
3
MH), 541 (100, LigH). UVꢀ
/
4H, CH2CO2), 2.24 (d, Jꢃ6.2 Hz, 6H, CHCH3), 1.78
/

48
H. Brunner, K.-M. Schellerer / Inorganica Chimica Acta 350 (2003) 39ꢀ48
/
3
[6] H. Brunner, K.-M. Schellerer, B. Treittinger, Inorg. Chim. Acta
264 (1997) 67.
(m, 4H, CH2), 1.08 (t, Jꢃ
(m, 4H, CH2), ꢂ3.67 (s, 2H, NH). PI-LISIMS
(glycerolꢀDMSO): m/z 1051 (65, MH), 846 (100, Mꢂ
OCH2CH2OCH2CH3ꢁH), 743 (55, LigH). UVꢀVis
/
6.2 Hz, 6H, CH2CH3), 0.87
/
[7] C. Lottner, K.-C. Bart, G. Bernhardt, H. Brunner, J. Med. Chem
45 (2002) 2064.
/
/
/
/
[8] C. Lottner, K.-C. Bart, G. Bernhardt, H. Brunner, J. Med. Chem.
45 (2002) 2079.
(DMSO): l (nm) (log o) 404 (4.48), 503 (3.40), 536
(3.19), 569 (3.11), 622 (2.75).
[9] H. Brunner, K.-M. Schellerer, Chem. Monthly 133 (2002) 679.
[10] B. Lippert, W. Beck, Chem. Unserer Zeit. 17 (1983) 190.
[11] J. Reedijk, Inorg. Chim. Acta 198ꢀ200 (1992) 873.
/
8.12.9. (2-Aminomethylpyridine-N,N?)[13,17-bis(2-
carboxylatoethyl)-3,8-bis(1-hydroxyethyl)-2,7,12,18-
tetramethylporphin-O,O?]platinum(II) (31)
Platinum complex 20, ligand hematoporphyrin in 40
ml of water. Yield: 100 mg (46%). Brown solid (m.p.ꢁ
[12] K.-M. Schellerer, Dissertation, Universitat Regensburg, Regens-
burg, 1996.
¨
[13] B.E. Maryanoff, A.B. Reitz, Chem. Rev. 89 (1989) 863.
[14] W.C. Groutas, D. Felker, Synthesis (1980) 861.
[15] I. Fleming, Chem. Soc. Rev. 10 (1981) 83.
[16] M. Lissel, K. Drechsler, Synthesis (1980) 459.
[17] B. Bogdanovic, A. Bolte, J. Organomet. Chem. 502 (1995) 109.
[18] D. Pini, A. Iuliano, C. Rosini, P. Salvadori, Synthesis (1990) 1023.
[19] J.M. Brown, B.A. Murrer, J. Chem. Soc., Perkin Trans. 2 (1982)
489.
/
250 8C). C40H44N6O6Pt (1091.99). IR (KBr): n 3420,
3300, 3220, 2970, 2910, 2840, 1600, 1370, 375 cmꢂ1. PI-
LISIMS (glycerolꢀ
/
DMSO): m/z 1169 (40, Mꢁ
/
DMSOꢁH), 1091 (50, MH), 599 (100, LigH). UVꢀ
/
/
[20] H. Brunner, P. Hankofer, U. Holzinger, B. Treittinger, H.
Schonenberger, Eur. J. Med. Chem. 25 (1990) 35.
¨
Vis (DMSO): l (nm) (log o) 402 (5.45), 502 (4.53), 535
(4.39), 570 (4.31), 622 (4.16).
[21] E. Holler, in: K.B. Keppler (Ed.), Metal Complexes in Cancer
Chemotherapy, VCH, Weinheim, 1993, p. 41.
[22] T.S. Mang, T.J. Dougherty, W.R. Potter, D.G. Boyle, S. Sommer,
J. Moan, Photochem. Photobiol. 50 (1989) 221.
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¨
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