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Статья Paper
Synthesis of Monohydroxy-Substituted Diarylporphyrins and Their Binding Ability towards Aminobenzoic Acids
Nugzar Zh. Mamardashvili,@ and Mikhail O. Koifman
Institute of Solution Chemistry of Russian Academy of Sciences, 153045 Ivanovo, Russia ®Corresponding author E-mail: ngm@isc-ras.ru
Synthesis of some new monohydroxy-substituted diarylporphyrins with different positions of the reactionary center in the macrocycle was performed. An ability of their zinc complexes to bind methyl esters of ortho-, meta- andpara-aminobenzoic acids in toluene was studied by spectrophotometric titration and HNMR spectroscopy.
Keywords: Zinc diarylporphyrinate, synthesis, binding ability, methyl ester of aminobenzoic acid, hydrogen bond, spectrophotometric titration, NMR spectroscopy.
Introduction
Porphyrins are widely used for binding of amino acids which usually occurs due to donor-acceptor interaction between NH-groups of amino acid and Zn11 atom of metalloporphyrinate.[1,2] In the case of zinc porphyrinates with OH groups the possibility of additional hydrogen bonds formation between the hydroxyl groups of porphyrinate and oxygen atom of amino acid appears. Hydrogen bonds in the resulting molecular complex make it significantly more stable.
When porphyrins form hydrogen bonds with amino acids (or with other biological objects) they are considered to be capable of recognizing the given substrates, and the higher the complex stability, the better is the recognizing ability of this porphyrin.
This work is devoted to the synthesis of new mono-hydroxysubstituted zinc porphyrinates with different positions of reactionary centres and investigation of their binding ability towards amino acids. To this end we used synthetic approach on the basis of key 10-arylsubstituted a,c-biladiene dihydrobromides which according to the literature data are widely employed for obtaining of mono-functionalized porphyrins.[3-6] By the method of spectrophotometric titration and 1H NMR spectroscopy a binding ability of the zinc porphyrinates (ZnP) regarding to the methyl esters of ortho- (L1), meta- (L2), and para- (L3) aminobenzoic acids in toluene have been studied.
Experimental
During the research were used commercially available aromatic aldehydes (2-hydroxybenzaldehyde, 2-hydroxymethylenoxybenzaldehyde and 4-hydroxyphenylen-(4-methylenoxy)benzaldehyde from Sigma and OttavaChemicals. 2,18-Dimethyl-3,7,8,12,13,17-hexaethyl-10-phenylbiladiene-a,c dihydrobromide was obtained as described earlier.[7] Zinc 10,20-diphenyl-2,8,12,18-tetramethyl-3,7,13, 17-tetraethylporphyrinate was obtained as described in [8]. Electronic absorption spectra were obtained in toluene using Cary 100 spectrophotometer. IR-spectra were obtained in tablets of KBr using spectrometer Specord
M-80. The mass spectra (electronic impact, 70 eV) were obtained on an MKh-1310 instrument (ion source temperature 150-200 0C). Reactions were monitored by thin layer chromatography and spectrophotometry. Neutral alumina (Merck; Brockmann activity grade II) was used for column chromatography.
10-Phenyl-20-(2-hydroxyphenylen)-2,18-dimethyl-3,7,8,12,13,17-hexaethylporphyrin (2). A solution of 2,18-dimethyl-3,7,8,12,13,17-hexaethyl-10-phenylbiladiene-a,c dihydrobromide (5.0 g, 0.6 mmol), 2-hydroxybenzaldehyde (0.10 ml, 1 mmol) and hydrobromic acid (1 ml, 46 %) was heated under reflux for 4 h in 50 ml of methanol. Iodine (0.10 g) was then added and the mixture was refluxed for additional 15 min. After cooling, the precipitate was filtered off, washed with methanol and dried. The crude porphyrin was dissolved in methylene chloride and subjected to chromatography on alumina (Brockmann activity grade II), with methylene chloride-methanol mixture (1:1) as an eluent. The eluate was partly evaporated, and the porphyrin was precipitated with methanol (0.11 g, 30% yield). Rf 0.27, (Al2O3, eluent - benzene). m/z (ESI): 675 (91 %) [(M+H)+]. UV-vis (toluene) ^max nm (lgs): 628 (3.06), 578 (3.59), 551 (3.23), 515 (4.14), 412 (4.98). *H NMR (CDCl3, 295 K) 8 ppm: 10.11 (2H, s, meso-H), 7.50 (3H, m, Ar-
H^oX 7 33 OH d ^etaX 724 № ^ ^-H^aX 712 № t, Ar-Hpara), 5.09 (1H, s, -OH), 2.97-2.92 (12H, m, CH2CH^„uail)t 2.28 (6H, s, C^) ), 1.11 (18H, t, CH2CH3(378 121317)), -3.03 (2H, bd. s., NH). IR (KBr) cm-1: vNH 3310, vOH 3213, 8Oh 1451, SNH 969,
Ynh 697, Vch 2980, 8ch 1502, Ych 83°.
10-Phenyl-20-(2-hydroxymethylenoxy)phenylen-2,18-dimethyl-3,7,8,12,13,17-hexaethylporphyrin (3) and 10-phenyl-20-[4-hydroxyphenylen-(4-methylenoxy)phenylen]-2,18-dimethyl-3,7,8,12,13,17-hexaethylporphyrin (4) were obtained similarly.
10-Phenyl-20-(2-hydroxy-methylenoxy)phenylen-2,18-di-methyl-3,7,8,12,13,17-hexaethylporphyrin (3). Yield 20 %. Rf 0.31 (Al2O3, eluent - benzene). m/z (ESI): 705 (96%) [(M+H)+]. UV-vis (toluene) ^max nm (lgs): 629 (3.29), 581 (3.85), 552 (3.40), 517 (4.36), 411 "(5.08). *H NMR (CDCl3, 295 K) 8 ppm: 10.19 (2H, s, meso-H), 7.70 (3H, m, Ar-Hortho), 7.53 (1H, d, Ar-Hmeta), 7.47 (3H, t, Ar-Hmeta), 7.32 (2H, t, Ar-HJ, 5.89 (1H, s, -OH), 3.61 (2H, s, 0CH2)a 2.18-2.12 (12H, mparCH2CH3(3 7 8 12 13 17)), 2.58 (6H, s, CH3(218)), 1.09 (18H, t, CH2CH3(3 7 8 12 13 17)),' ■-3.01 (2H, bd.s., NH).
IR (KBr) cm-1: Vnh 3315, Voh 3217, ^oh 1455, V coc 1260, v„ c-o-c 1232, 8nh 969, Ynh 697, v^ 2986, 8ch 1501, y^ 837.
10-Phenyl-20-[4-hydroxyphenylen-(4-methylenoxy) phenylen]-2,18-dimethyl-3,7,8,12,13,17-hexaethylporphyrin (4). Yield 23%. Rf 0.37, (Al2O3, eluent - benzene). m/z (ESI): 780
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Макрогетероциклы /Macroheterocycles 2011 4(1) 30-33
(83%) [(M+H)+]. UV-vis (toluene) Xmax nm (lge): 630 (3.32), 583 (3.92), 553 (3.45), 518 (4.44), 412 (5.11). 'H NMR (CDCl3, 295 K) 8 ppm: 10.23 (2H, s, meso-H), 7.52 (4H, d, Ar-Hortho), 7.22 (4H, d, Ar-H t), 5.17 (1H, s, -OH), 3.71 (2H, s, OCH2), 2.20-2.16
(12H, m, CH2CH CH„CH,
^ 3(3,7.8.12,13.17)
), 2.52 (6H, s, CH3(218)), 1.12 (18H, t
3(3 78121317)), -3.05 (2H, bd.s., NH). IR (KBr) cm-1: Vnh 3320, V0H 32273 S0H M60, V c.0.c 1276, V^coc 1243, Snh 971, YNH 691, Vch 2990, Sch 1510, Ych 841
Zinc 10-phenyl-20-(2-hydroxyphenylen)-2,18-dimethyl-3,7,8,12,13,17-hexaethylporphyrinate (5). 10 times excess of zinc acetate was added to the solution of 10-phenyl-20-(2-hydroxyphenyl)-2,18-dimethyl-3,7,8,12,13,17-hexaethylporphyrin (30 mg) in dimethylformamide (70 ml) and the reactionary mixture was heated under reflux for 30 min. On cooling the solution was diluted with water (1:1), the precipitated substances were filtered off and dried at room temperature. The crude porphyrin was dissolved in methylene chloride and subjected to chromatography on alumina (Brockmann activity grade II), with methylene chloride-hexane mixture (1:1) as an eluent. The eluate was partly evaporated, and the porphyrin was precipitated with methylene chloride-methanol mixture (1:2) (24.70 mg, 83% yield). R7 0.40, (Al2O3, eluent -benzene). UV-vis (toluene) X nm (lge): 578 (3.56), 542 (3.99), 410 (4.92). IR (KBr) cm-1: vj^ 320, Voh 3210, Soh 1448, Snh 978, Ynh 689, vcH 2987, ScH 1512, ych 838. 1H NMR (CDCl3, 295 K) 8 ppm: 10.13 (2H, s, meso-H), 7.52 (3H, m, Ar-Hortho), 7.31 (1H, d, Ar-H f), 7.22 (3H, t, Ar-H f), 7.10 (2H, t, Ar-H °), 5.11 (1H, s,
meta7' v ' ' meta7' v ' ' para7' v ' '
-OH), 3.0°-2.82 (12H, m, CHt^^ 2.22 № ^ CH3(218) ),
1.15 (18H, t, CH2CH3(3 78 12 13 17)). 1H NMR for the complex 5-L1 (CDCl3, 295 K) 8 ppm: "l°."l(:) (2H, s, meso-H), 7.49 (3H, m, Ar-H „ ), 7.28 (1H, d, Ar-H f), 7.17 (3H, t, Ar-H f), 7.05 (2H, t, Ar-
ortho meta meta
Hpara), 6.28 (2H, m, L-H), 5.11 (1H, s, -OH), 4.53 (3H, s, L-OCH3),
3.83 (2H, t, L-H), 3.02-2.86 (12H, m, CHCH
), 2.23 (6H,
3(3,7,8,12,13,17)
s, CH3(2,18) ),1.56 (2H, S, ^^ 1.18 (18H t, CH2CH3(3 7 ,1,13,7)).
Zinc 10-phenyl-20-(2-hydroxymethylenoxy)phenylen-2,18-dimethyl-3,7,8,12,13,17-hexaethylporphyrinate (6) and zinc 10-phenyl-20-[4-hydroxyphenylen-(4-methylenoxy)phenylen]-2,18-dimethyl-3,7,8,12,13,17-hexaethylporphyrinate (7) were obtained similarly.
Zinc 10-phenyl-20-(2-hydroxymethylenoxy)phenylen-2,18-dimethyl-3,7,8,12,13,17-hexaethylporphyrinate (6). Yield 86%. R^ 0.49, (Al2O3, eluent - benzene). UV-vis (toluene) A,max nm (lge): 579 (3.57), 540 (3.98), 412 (4.91). IR (KBr) cm-1: vNH"3311, voh
3217, S0H 1455, Vs c.o.c 1260, Vas c-o-c 1232, SNH 973, Ynh 698, V^
2984, ScH 1501, ycH 839. 1H NMR (CDCl3, 295 K) S ppm: 10.05 (2H, s, meso-H), 7.55 (3H, m, Ar-Hortho), 7.31 (1H, d, Ar-Hmeta), 7.20 (3H, t, Ar-H f), 7.02 (2H, t, Ar-H ), 5.92 (1H, s, -OH),
meta para
3.61 (2H, s, 0CH2), 2.78-2.54 (12H, m, CH2CH3 (3781213 17)), 2.28 (6H, s., CH3(218)), 1.04 (18H, t, CH2CH3(3 7 8 12 13 17)). (H NMR for the complex 6-L2 (CDCl3, 295 K) S ppm: 10.02 (2H, s, meso-H), 7.51 (3H, m, Ar-H th), 7.32 (1H, d, Ar-H t), 7.19 (3H, t, Ar-H t), 7.00
ortho meta meta
(2H, t, Ar-Hpara), 6.70 (1H, s, -OH), 6.35 (3H, m, L-H), 4.55 (3H, s, L-OCH3), 3.81 (1H, s, L-H), 3.57 (2H, s, 0CH2), 2.72-2.50 (12H,
m, CH2CH3(3.7.8.12.13.17)), 2.24 (6H, S., CH3 (,18) ), 1270 (2H, S, L-NH2), 1.01 (18H,t C^2^H3(3,A1,1,17)).
Zinc 10-phenyl-20-[4-hydroxyphenylen(4-methylenoxy)-phe-nylen]-2,18-dimethyl-3,7,8,12,13,17-hexaethylporphyrinate (7). Yield 84%. R 0.53, (Al2O3, eluent - benzene). UV-vis (toluene) I nm (lge): 581 (3.63X 543 (3.97), 410 (5.15). IR (KBr) cm-1:
C 33160, Voh 3222, S0H 1462, Vs c-0-c 1266, V^ c-o-c 1247, SNH 971,
Ynh 690, vcH 2993, ScH 1510, ych 841. 1H NMR (CDCl3, 295 K) S ppm: 10.2H1 (2H, s, meso-H), 7.54 (4H, d, Ar-Hoitio), 7.23 (4H, d, Ar-H t), 5.17 (1H, s, -OH), 3.74 (2H, s, 0CH2), 2.21-2.17 (12H, nTCH2CH3(3,8,,1,17)), 2.4 (6H, s., CH3(218) ), 1.10 (18H, t, CH2CH3(3 7 8 12 13 17)). 1H NMR for the complex 7-L- (CDCl3, 295 K) S ppm: 10.19 (2H, s, meso-H), 7.51 (4H, d, Ar-HortJ, 7.20 (4H, d, Ar-Hmeta), 6.22 (2H, m, L-H), 5.63 (1H, s, -OH), °4.53 (3H, s, L-OCH3m)e, 3.86 (2H, t, L-H), 3.71 (2H, s, 0CH2), 2.18-2.12 (12H, m, CH2C}^,(X1X1%1X17;), 2.3 (6H, s., CH3(2,18) ), 1.53 (2H, s, L-N]), 1.07
(18H, t, CH2CH3(3 7 8 12 13 17)). 1H NMR for the complex 7-L2 (CDCl3, 295 K) S ppm: 10.20 (2H, s, meso-H), 7.56 (4H, d, Ar-Hortho), 7.24 (4H, d, Ar-Hmeta), 6.37 (3H, m, L-H), 5.47 (1H, s, -OH), 4.5°5 (3H, s, L-OCH3), 3.84 (1H, s, L-H), 3.76 (2H, s, 0CH2), 2.23-2.15 (12H,
m, CH2CH3(3.,,1,13.17)), 2.51 (6H, S., CH3(2.18)), 1.65 (2H, ^ L-NH2),
1.13 (18H, ^ CH2CH3(,,,1,1,17)).
The reactions of L--L3 with ZnP were studied by spectrophotometric titration method on the increasing and decreasing wavelengths as described earlier.[9,10] Before titration, a solution of ZnP in toluene with 6T0-6 M concentration and a solution of amino acid with a fixed concentration were placed into 1 cm quartz cell (the measurements were performed at 20 0C). The optical density was measured on two wavelengths, where its changes were almost the same. The stability constant (K) was calculated as follows:
[ZnPL] [ZnP][L]
= l/c
AA[ &A°h AA? AAi
where is the wavelength with decreasing intensity, X2 is the wavelength with growing intensity, c is the concentration of amino acid, A0 is the maximum change of optical density at the given wavelength, A' is the optical density of solution at the given wavelength and at the given concentration. The error of Ka determination was ± 10%.
The cocentration interval of amino acid ester solutions, where the changes of the optical density are observed, ranges from (7-10)-10-6 M to (7-10)-10-4 M depending on the porphyrinate type. The smaller the concentration interval with the observed changes in the optical density the better is the recognizing capability of porphyrinate.
The dependence of the formation of amino acid - ZnP associates on the position of hydroxy-substituents in a macrocycle was confirmed by the method of 1H NMR spectroscopy. 1H NMR spectra were recorded on a Bruker AC-500 spectrometer at 500.17 MHz. Chemical shifts are given in ppm from tetramethylsilane (TMS); solvent - deuterochloroform.
Results and Discussion
By the reaction of 10-phenylsubstituted a,c-biladiene dihydrobromide - with corresponding aromatic aldehydes new mono-hydroxysubstituted porphyrins 2-4 were obtained. The strength of organic acids (trifluoroacetic acid, chloroacetic acid, acetic acid) used as the catalyst only slightly effects on the yield of the target products 2-4. Hydrobromic acid is the most convenient and provides the optimum yield (30%).
X = 2-OH (2,5), 2-0cH20H (3,6), 4-0cH2c6H4(4-0H) (4,7); M = H2 (2-4), Zn (5-7)
Heating of the porphyrins 2-4 with zinc acetate in dimethylformamide allowed obtaining zinc porphyrinates
Hydroxy-Substituted Diarylporphyrins
5-7 with the yield of 85%. The spectral characteristics of 2-7 are in full agreement with the proposed structures.
alcohols.[10,11] The ligands L1-L3 are most similar to pyridine (K = 5000 M-1) in their extra coordination properties.
Figure 1. a) Changes of the UV-vis spectra of 5 upon addition of L1 in toluene; b) binding isotherm of the complexation (C , = 6.2106 M, C = 0-8.6 10-3 M).
v porph. 7 ester /
The Figure 1 shows changes of the electron absorption spectrum in the Soret region upon addition of L1 methyl ester to porphyrinate 5. The presence of isosbestic points in the UV-vis spectra of the reactionary system, one step titration curve of the complexation and the data of 1H NMR spectroscopy of 5 - L1 complex indicate the formation of complex 8 with reagents ratio of 1:1. Since the processes of extra coordination of amino acids to zinc porphyrinates were the subjects of our previous studies[9,10] we shall not consider this topic in details in this work.
The stability constants determined for 8 are similar for the complexes 9 between zinc 10,20-diphenyl-2,8,12,18-tetramethyl-3,7,13,17-tetraethylporphyrinate 10 (porphyrin without hydroxy-group) and L1-L3 (Table 1). Basing on the results we can conclude that 8 and 9 are the complexes with a single binding point (through coordination to ZnII).
By comparison of the obtained Ka values with published data for analogous complexes of tetraphenylporphyrin in toluene, we should admit that L1-L3 are less strong extraligands than piperidine (Ka = 80900 M-1), imidazole (Ka = 24000 M-1) and quinoline (Ka = 16900 M-1) but considerably stronger than pyrrole (Ka = 200 M-1), methanol (Ka = 5 M-1) and other
cH3o,
Table 1. Stability constants (Ka*, M-1) of zinc porphyrinates 5-7 and 10 with amino acids methyl esters in toluene at 200C.
Porphyrinate L1 L2 L3
5 1020 1050 990
6 980 3380 960
7 2420 1730 870
10 1009 1023 979
* The error of K determination is ~7%
Changes of the electron absorption spectra upon addition of L1-L3 to the porphyrinate 6 or 7 are similar to that during
Figure 2. XH NMR spectra of 6 and 6-L2 (11 ) in CDCl3 at 25 0C.
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Макрогетероциклы /Macroheterocycles 2011 4(1) 30-33
the complexation of 5 with L- But the reactionary system saturation occurs at less concentration of the reagents and the interactions are characterized by higher stability constants (Table 1). A sharp increasing of the stability constants in the systems 6-L2, 7-L1 and 7-L2 could be explained by the formation of the complexes 11, 12 with two binding points through coordination to Zn" and additional hydrogen bonding between hydroxy-group of porphyrinate and oxygen atom of amino acid.
a)
b)
Figure 3. Top (a) and side (b) views of structure of complex 11 optimized by semi-empirical method AM1.
Formation of the complexes was also studied by 1H NMR spectroscopy. In the spectra of complex 11 the OH signal is shifted downfield by 0.8 ppm (Figure 2). The similar shifts (5 = 0.5 and 0.3 ppm, correspondingly) were observed for the complexes 12. According to the literature data[1] and results of our own calculations (Figure 3), the formation of the strong hydrogen bonds between the carbonyl oxygen atom of amino acid and hydrogen atom of porphyrinate's hydroxy-group is confirmed.
Conclusions
Thus, the developed synthetic methods allow obtaining hydroxysubstituted porphyrinates, which due to the good geometrical conformity between the reactionary centers
of the reagents are able to coordinate ortho- and meta-aminobenzoic acids simultaneously through the central metal cation and hydroxy group on the macrocycle's periphery. Selectivity and high sensitivity of porphyrins to low-energy effects make the tetrapyrrolic macrocycles to be the ideal candidates for the substrates determination, separation and extraction.
Acknowledgements. The work was done with the support of Federal Purposeful Program «Research and educational staff of Russia in 2009-2013» (State contract № 02.740.11.0857) and the Seventh Framework Program of the European Community for Research, Technological Development and Demonstration Activities (Grant Agreement Number: IRSES-GA-2009-247260).
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Received 21.10.2010 Accepted 27.01.2011
