Complexation of Zn arylporphyrinates with leucine methyl ester

Article abstract of DOI:10.1023/B:RUCO.0000030157.98943.43

Extra coordination of L-leucine methyl ester with seventeen different Zn arylporphyrinates is studied by spectrophotometric titration and capability of Zn porphyrinates with the active OH groups to recognize LeiOCH₃ in toluene at 20°C is determined. The formation of associates of the composition amino acid etherporphyrinate depending on the substituent positions in a macrocycle is studied by the ¹H NMR method. The most strong donor-acceptor bonds between Zn porphyrinate and LeiOCH₃ are observed in the case of pyridine-substituted porphyrins and porphyrins with phenyl rings containing electron-donor substituents in the m-position. The best recognizing capabilities with respect to leucine are shown by Zn porphyrinates with di- and tetra-4-OH-phenyl substitution in the meso-positions of a macrocycle.

Full text of DOI:10.1023/B:RUCO.0000030157.98943.43

Russian Journal of Coordination Chemistry, Vol. 30, No. 6, 2004, pp. 388–391. Translated from Koordinatsionnaya Khimiya, Vol. 30, No. 6, 2004, pp. 416–420.
Original Russian Text Copyright © 2004 by G. Mamardashvili, Storonkina, N. Mamardashvili.
Complexation of Zn Arylporphyrinates
with Leucine Methyl Ester
G. M. Mamardashvili*, O. E. Storonkina**, and N. Zh. Mamardashvili*
*Institute of Solution Chemistry, Russian Academy of Sciences, ul. Akademicheskaya 1, Ivanovo, 153045 Russia
**Ivanovo State University, Ivanovo, Russia
Received March 18, 2003
Abstract—Extra coordination of L-leucine methyl ester with seventeen different Zn arylporphyrinates is stud-
ied by spectrophotometric titration and capability of Zn porphyrinates with the active OH groups to recognize
LeiOCH3 in toluene at 20°ë is determined. The formation of associates of the composition amino acid ether–
porphyrinate depending on the substituent positions in a macrocycle is studied by the 1H NMR method. The
most strong donor–acceptor bonds between Zn porphyrinate and LeiOCH3 are observed in the case of pyridine-
substituted porphyrins and porphyrins with phenyl rings containing electron-donor substituents in the m-posi-
tion. The best recognizing capabilities with respect to leucine are shown by Zn porphyrinates with di- and tetra-
4-OH-phenyl substitution in the meso-positions of a macrocycle.
The study of interaction between porphyrin mole- higher the complex stability, the better the recognizing
cules and the protein surrounding in biological systems capability of this porphyrin.
is one of the topical lines of research in biochemistry
Porphyrins with the high recognizing capability are
today. The reaction of porphyrins with amino acids and
used for selective binding of amino acids, for their
proteins can occur in different ways, namely, through
chiral recognition, and for modeling artificial receptors
the formation of covalent bonds or ionic association in
[1–5].
aggregates, via the donor–acceptor interaction or
The structure and composition of molecular com-
hydrogen bonds between separate covalently bonded
plexes porphyrin–amino acid are studied by the NMR,
fragments. In the latter case, so called self-organizing
circular dichroism, and other methods, while their for-
systems are formed.
mation constants (association constants) are obtained
from the spectrophotometric titration data.
This work is devoted to the study of molecular com-
plexes of zinc arylporphyrinates (ZnP) with leucine
methyl ester (LeiOCH3) in toluene. Such complexes are
formed due to donor–acceptor interaction between NH2
groups of amino acid and Zn(II) atom of metallopor-
phyrinate, whereas in the case of zinc arylporphyrinates
with OH groups, they are formed also due to hydrogen
bonds –éç···é= formed between the hydroxyl groups
of porphyrinate and the oxygen atom of amino acid:
Table 1. Association constants for ZnP(OCH3Lei) com-
plexes in toluene at 20°C
ka,
ka,
Complex
Complex
(mol/l)–1
(mol/l)–1
I–LeiOCH3
1370
1660
2060
1760
1120
2040
1380
1790
1105
C H
4
9
H
II–LeiOCH3
IV–LeiOCH3
VI–LeiOCH3
VIII–LeiOCH3
X–LeiOCH3
III–LeiOCH3
V–LeiOCH3
2790
1670
2560
1850
2480
1390
2720
1950
CO CH
2
3
NH
Zn
2
VII–LeiOCH3
IX–LeiOCH3
XI–LeiOCH3
XIII–LeiOCH3
XV–LeiOCH3
XVII–LeiOCH3
HO
OH
ZnP(OCH3Lei)
XII–LeiOCH3
XIV–LeiOCH3
XVI–LeiOCH3
Hydrogen bonds in the molecular complex
ZnP(OCH3Lei) make it significantly more stable. When
porphyrins form hydrogen bonds with amino acids (or
with the other biological objects) they are considered to
be capable of recognizing the given amino acid, and the
1070-3284/04/3006-0388 © 2004 åÄIä “Nauka /Interperiodica”

COMPLEXATION OF ZN ARYLPORPHYRINATES
389
The spectrophotometric titration and NMR meth- donor–acceptor interaction with LeiOCH3 and on the
ods are used in this work in order to study the associa- formation of hydrogen bonds between them in the
tive complexes ZnP(OCH3Lei) containing different case of zinc porphyrinates with OH groups. The struc-
porphyrinates and to establish the effect of the struc- tures of porphyrinates I–XVII under study are given
ture of separate fragments of Zn porphyrinate on its below:
X1 = X2 = X3 = X4 = H
(I)
(II)
(III)
(IV)
(V)
X1 = X3 = Ph; X2 = X4 = H
X1 = X3 = Py; X2 = X4 = H
X1 = X2 = X3 = Ph; X4 = H
X1 = X2 = X3 = Py; X4 = H
X1 = X2 = X3 = X4 = Ph
X1 = X2 = X3 = X4 = Py
X4
Zn
X2
C4H9
C4H9
(VI)
(VII)
CH3
X1
CH3
CH3
X3
N
N
X1 = X2 = (4-OCH3Ph); X2 = X4 = H (VIII)
N
N
X1 = X2 = (4-OHPh); X2 = X4 = H
X1 = X2 = (3-OCH3Ph); X2 = X4 = H
X1 = X2 = (3-OHPh); X2 = X4 = H
X1 = X2 = (2-OCH3Ph); X2 = X4 = H
X1 = X2 = (2-OHPh); X2 = X4 = H
X1 = X2 = X3 = (4-OCH3Ph); X4 = H
X1 = X2 = X3 = (4-OHPh); X4 = H
X1 = X2 = X3 = X4 = (4-OCH3Ph)
(IX)
(X)
(XI)
(XII)
(XIII)
(XIV)
(XV)
(XVI)
CH3
C4H9
C4H9
X1 = X2 = X3 = X4 = (4-OHPh)
(XVII)
EXPERIMENTAL
was added and the mixture was stirred for 1 h. Then,
5ml of methanol was added and the stirring was contin-
ued for another 30 min. the solution obtained was neu-
tralized with ammonia solution, evaporated, and chro-
matographed on silica gel with chloroform. The yield
was 98.5 mg (97%). Rf = 0.76, silufol, ethylacetate–
heptane (3 : 1). IR spectrum (KBr pellets), ν, cm–1:
3300 (ν (O–H)), 1345 (δ(O–H)), 1275 (ν(C–O)). The
electronic absorption spectrum, λmax, nm (logε): 570.7
The following complexes were synthesized using
the corresponding procedures: I [6]; II, III, X, XII [7];
IV, V, XIV [8]; VI, VII, XVI [9]; XV–XVII [10]. L-
leucine methyl ester was synthesized from the corre-
sponding amino acid following the procedure [11].
Synthesis of Zn-trans-5,15,-di(4-methoxyphen-
yl)-2,8,12,18-tetrabutyl-3,7,13,17-tetramethylpor-
phyrin (VIII) [10]. The yield was 94%. The electronic
absorption spectra, λmax, nm (logε): 573.7 (3.88), 536.1
(3.62), 401.9 (5.16). The 1H NMR spectrum of porphy-
rinate VIII, δ, ppm: 10.19 (s, 2H meso-H), 7.76 (d, 2H,
Ó-phenyl), 7.65 (m, 6H, m-, o-phenyl), 5.14 (s, 1H,
OH), 3.96 (t, 8H, β-CH2CH2CH2CH3), 2.51 (s, 12H, β-
CH3), 2.16 (p, 8H, β-CH2CH2CH2CH3), 1.62 (sq, 8H, β-
CH2CH2CH2CH3), 1.02 (t, 8H, β-CH2CH2CH2CH3).
1
(3.95), 533.1 (3.60), 403.3 (5.20). The H NMR spec-
trum of porphyrinate IX, δ, ppm: 10.01 (s, 2H, meso-
H), 7.86 (d, 4H, Ó-phenyl), 7.19 (d, 4H, m-phenyl), 4.94
(s, 1H, OH), 3.85 (t, 8H, β-CH2CH2CH2CH3), 2.42 (s,
12H, β-CH3), 2.10 (p, 8H, β-CH2CH2CH2CH3), 1.61
(sq, 8H, β-CH2CH2CH2CH3), 0.99 (t, 8H, β-
CH2CH2CH2CH3).
The 1H NMR spectrum of the IX–LeiOCH3 associ-
ate, δ, ppm: 10.02 (s, 2H, meso-H), 7.89 (d, 4H, Ó-phe-
nyl), 7.21 (d, 4H, m-phenyl), 5.73 (s, 1H, OH), 3.82 (t,
8H, β-CH2CH2CH2CH3), 2.40 (s, 12H, β-CH3), 2.13 (p.
8H, β-CH2CH2CH2CH3), 1.64 (sq, 8H, β-
CH2CH2CH2CH3), 1.02 (t, 8H, β-CH2CH2CH2CH3).
1
The H NMR spectrum of the associate of leucine
methyl ester with porphyrinate VIII, δ, ppm: 10.16 (s,
2H, meso-H), 7.80 (d, 2H, Ó-phenyl), 7.62 (m, 6H, m-,
o-phenyl), 5.52 (s, 1H, OH), 3.93 (t, 8H, β-
CH2CH2CH2CH3), 2.54 (s, 12H, β-CH3), 2.12 (p, 8H, β-
CH2CH2CH2CH3), 1.60 (sq, 8H, β-CH2CH2CH2CH3),
1.00 (t, 8H, β-CH2CH2CH2CH3).
The elemental analysis of the IX–LeiOCH3 associ-
ate:
Synthesis
of
Zn-5,15-di(4-hydroxyphenyl)-
2,8,12,18-tetrabutyl-3,7,13,17-tetramethylporphy-
rin (IX). To a solution of porphyrinate VIII (105 mg,
0.13 mmol) in 10 ml of chloroform, a solution of boron
tribromide (0.15 ml, 1.57 mol) in 5 ml of chloroform
For C52H62N4O4Zn
Anal. calcd. (%): C, 71.64; H, 7.12; N, 6.43; Zn, 7.46.
Found (%):
C, 71.61; H, 7.10; N, 6.40; Zn, 7.43.
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 30 No. 6 2004

390
MAMARDASHVILI et al.
Table 2. Energy of hydrogen bonds (∆Ghyd.b), extra coordination (∆Gextr), and total free energy of association (∆Gtot) of Zn
porphyrinate–LeiOCH3
Complex
IX–LeiOCH3
∆Gtot, kJ/mol*
∆Gextr, kJ/mol*
∆Ghyd.b, kJ/mol*
Reference porphyrin
–17.95
–18.56
–17.32
–18.93
–18.13
–16.80
–18.23
–17.32
–17.93
–16.77
–1.15
–0.33
0
VIII
X
XI–LeiOCH3
XIII–LeiOCH3
XV–LeiOCH3
XII
XIV
XVI
–1.00
–1.36
XVII–LeiOCH3
* ∆G = –RTlnk ; ∆G
'
''
= –RTln(k /k ); ∆G = ∆G – ∆G .
hyd.b
tot
a
hyd.b
extr
tot
a
a
The syntheses of Zn-5,15-di(3-hydroxyphenyl)- (KBr pellets). The electronic absorption spectra were
2,8,12,18-tetrabutyl-3,7,13,17-tetramethylporphyrin
measured in chloroform on a Specord M40 spectropho-
(XI)
and
Zn-trans-5,15-di(2-hydroxyphenyl)- tometer.
2,8,12,18-tetrabutyl-3,7,13,17-tetramethylporphyrin
(XIII) were carried out analogously.
RESULTS AND DISCUSSION
The reactions of LeiOCH3 with porphyrinates I–
XVII were studied by spectrophotometric titration with
the increasing and decreasing wave lengths as described
in [1–5]. Before titration, a solution of zinc porphyrinate
in toluene with concentration ~6 × 10–6 mol/l and a solu-
tion of amino acid with a specific concentration were
placed in a 1-cm quartz cell (the measurements were
performed at 20°ë). The optical density was measured
at two wave lengths, where its changes were almost the
same. The association constant (ka) was calculated as
follows
The association constants (Table 1) for complexes
of porphyrinates I–VIII, X, XII, XIV, and XVI with
LeiOCH3 are in fact constants of extra coordination that
determine the stability of the porphyrinate–extra ligand
complexes.
Zinc is a typical Group II metal. The cations of this
group have formal charge +2 and are disposed to the
sp3- and d2sp3- hybridization. They are forced to acquire
the dsp2-configuration under the influence of a rigid
porphyrin ligand. The Zn2+ cations firmly bind one N-
donor extra ligand and form M(L)P and weakly coordi-
nate the oxygen- and sulfur-containing molecular
ligands.
As regards their capability to coordinate to Zn por-
phyrinate as extra ligands, amino acids are intermediate
between pyridine and pyrrole, for which the stability
constants of their complexes with Zn porphyrinate in
toluene are, respectively, 5700 and 200 [12].
Depending on the nature of porphyrin, the stability
constant of complexes M(L)P (in our case, ka) changes
2–3 times as maximum. This is supported by the data
[12] and by our data (Table 1).
∆Di ∆D



0λ 
λ1
[ZnPL]
2
----------------------
k = ----------------------- = 1 / c
,

a
∆D0 ∆Di
[ZnP][L]
λ 
λ1
2
where λ1 is the decreasing wave length, λ2 is the
increasing wave length, c is the concentration of amino
acid ether, D0 is the maximum change in the optical
density of a solution at the given wave length, Di is the
optical density of a solution at the given wave length
and at the given concentration. The error of determina-
tion ka was 10%.
The concentration interval of solutions of the
amino acid ether where the changes in the optical density
are observed ranges from (7–10) × 10–6 to (7–100) ×
10−4 mol/l depending on the porphyrinate type. The
smaller the concentration interval with the observed
changes in the optical density the better the recognizing
capability of porphyrinate.
In general, the introduction of aryl substituents
(phenyl or pyridine substituents) into the porphyrin
molecule increases ka, which agrees with the concepts
of the electronic structure of M(L)P.
Substituents with the negative induction effect (with
respect to porphyrin) diminish the electron density in a
The formation of associates of the composition macrocycle and thus make the bond Zn–extra ligand in
amino acid–zinc porphyrinate depending on the posi- the complex less stable. Such substituents include the
tion of substituents in a macrocycle was investigated by phenyl and pyridine substituents, phenyl rings with the
1
the H NMR method. The spectra were recorded on a electron-acceptor substituents, independent of the posi-
Bruker 200 instrument with the working frequency tions of the latter in the aryl fragment, and the phenyl
200 MHz at 21°ë with deuterochloroform as a solvent. rings with the electron-donor substituents in the m-posi-
IR spectrum was taken on a Specord M80 spectrometer tion. The positive induction effect with respect to the por-
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 30 No. 6 2004

COMPLEXATION OF ZN ARYLPORPHYRINATES
391
phyrin molecule is exhibited by the aryl groups with the position of substituents in the phenyl fragments of a
1
electron-donor substituents in positions 2 and 4.
macrocycle was also studied by the H NMR method.
In the presence of LeiOCH3 (with a fivefold excess of
amino acid ether with respect to porphyrinate), the
spectrum of porphyrinate IX exhibits a downfield shift
of a signal from a proton of the OH group of the phenyl
fragment (by 0.8 ppm). This fact, according to the data
in [1], suggests the formation of the strong hydrogen
bonds between the carbonyl oxygen atom of amino acid
and the hydrogen atom of the hydroxy-substituted frag-
ment of a macrocycle.
Thus, the stability of the Zn–LeiOCH3 bond in phe-
nylporphyrinates increases, while in the CH3O- and
OH-phenylporphyrinates (with substituents in position
4) decreases as compared to phenylporphyrinates II,
IV, VI and with octaalkylporphyrinate I. The effect of
the CH3O- and OH-substitution in the phenyl rings on
extra coordination is almost identical. The number and
symmetric location of the phenyl and pyridine rings in
a macrocycle only slightly influence the strength of the
Zn–LeiOCH3 bond (Table 1).
Thus, the capabilities of Zn arylporphyrinates to
recognize leucine methyl ester in toluene depends on
the position of hydroxy groups in the phenyl fragments.
The best recognizing capabilities with respect to leu-
cine methyl ester are shown by Zn phenylporphyrinates
with hydroxy groups in position 4. The most strong
extra coordination of leucine methyl ester is observed
Porphyrinates IX, XI, XIII, and XVII have potenti-
alities of forming hydrogen bonds between the OH
group of porphyrinate and the ëOOCH3 group of leu-
'
''
'
cine methyl ester. The ratio ka/ka (where ka is the con-
stant of association of porphyrinate with hydroxy
''
group, ka is the constant of association of porphyrinate in the case of pyridine-substituted porphyrinates and
porphyrinates with the phenyl rings containing elec-
tron-donor substituents in position 3.
with the similar structure but without hydroxy group) is
a quantitative measure of an increase in the association
strength due to hydrogen bond formation. As seen from
Table 1, the hydrogen bonds are not always formed
between the oxygen atom of amino acid ether and the
hydrogen atom of hydroxyl group of porphyrinate,
when amino acid ether is coordinated to metallopor-
phyrinate and the hydroxy group is incorporated in por-
phyrinate.
ACKNOWLEDGMENTS
This work was supported by INTAS (project
no. YSF-00-37).
REFERENCES
Of the three porphyrinates IX, XI, and XIII that dif-
fer in the position of the hydroxy group in the phenyl
ring, the hydrogen bonds are formed only in the cases
where the hydroxy group is in position 4. For the hydro-
gen bond to be formed, the ester groups of LeiOCH3
should lie at a specific angle with respect to the hydroxy
groups of porphyrin. This angle should be determined
by the steric repulsion between the bulky substituent in
amino acid ether (R = –ëç2ëç(ëç3)2 in LeiOCH3)
and the porphyrin plane. These steric repulsions are
likely to send the ester groups toward the hydroxy
groups and to give the conformation favorable for the
formation of hydrogen bonds. That is why position 4 in
the phenyl ring is, evidently, the most favorable posi-
tion for the formation of hydrogen bonds.
The formulas in footnote to Table 2 were used to cal-
culate the contributions to the total energy of formation
of associate (∆Gtot) of the energy of extra coordination
(∆Gextr) and of H bonds (∆Ghyd.b). One can see that the
highest energy of hydrogen bonds that are formed in the
ZnP(OCH3Lei) complexes is 1.36 kJ/mol.
1. Mizutani, T., Ema, T., Yoshida, T., et al., Inorg. Chem.,
1993, vol. 32, no. 10, p. 2072.
2. Mizutani, T., Ema, T., Tomita, T., et al., J. Am. Chem.
Soc., 1994, vol. 116, no. 10, p. 4240.
3. Ogoshi, H., Hatakeyama, H., Yamamura, K., and
Kuroda, Y., Chem. Lett., 1990, vol. 19, no. 1, p. 51.
4. Ogoshi, H., Hatakeyama, H., Kotani, J., et al., J. Am.
Chem. Soc., 1991, vol. 113, no. 21, p. 8181.
5. Král, V. and Sessler, J.L., Tetrahedron, 1995, vol. 51,
no. 4, p. 539.
6. Jackson, A.H., Kenner, G.W., and Wass, J., J. Chem.
Soc., Perkin Trans. 1, 1972, no. 10, p. 1475.
7. Mamardashvili, N.Zh., Semeikin,A.S., Golubchikov, O.A.,
and Berezin, B.D., Zh. Org. Khim., 1993, vol. 29, no. 6,
p. 1213.
8. Mamardashvili, N.Zh., Semeikin, A.S., Golubchi-
kov, O.A., and Berezin, B.D., Abstracts of Papers, III
Vsesoyuz. konf. po khimii i biokhimii makrotsikl. soedin.
(III All-Union Conf. on the Chemistry and Biochemistry
of Macrocyclic Comp.), Ivanovo, 1988, p. 318.
9. Adler, A.D., Longo, F.R., and Finarelli, J.D., J. Org.
Chem., 1967, vol. 32, no. 2, p. 476.
The amount of the phenyl fragments containing the
hydroxy groups also affects the value of ka, but to a
lesser extent. The maximum difference is observed in
the cases with the symmetric and asymmetric positions
of the phenyl rings.
10. Mamardashvili, N.Zh., Cand. Sci. (Chem.) Dissertation,
Ivanovo, 1990.
11. Brenner, M. and Huber, W., Helv. Chim. Acta, 1953,
vol. 36, no. 8, p. 1109.
The formation of associates of the composition
amino acid ether–Zn porphyrinate depending on the
12. Berezin, B.D. and Enikolopyan, N.S., Metalloporfiriny
(Metalloporphyrins), Moscow: Nauka, 1988.
RUSSIAN JOURNAL OF COORDINATION CHEMISTRY Vol. 30 No. 6 2004