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4Porphyrins Порфирины
Шкрогэтароцмклы
http://macroheterocycles.isuct.ru
Paper Статья
DOI: 10.6060/mhc213945b
Formation of Associates of Porphyrins and Water in C6D6 Medium
Dmitriy V. Belykha@ and Alexander L. Stolypkob
aInstitute of Chemistry of Komi Scientific Centre of Ural Branch of Russian Academy of Sciences, 167000 Syktyvkar, Russian
Federation
hPitirim Sorokin Syktyvkar State University, 167001 Syktyvkar, Russian Federation
@Corresponding author. E-mail: [email protected]
Using the DOSY method, the equilibrium constants (KJ for the formation - decomposition of molecular associates for a number of porphyrins and chlorins with a water molecule in the C6D6 medium were determined. Kc and the proportion of porphyrin-bound water were determined experimentally from the dependences of the self-diffusion coefficients D on the diffusion time tm, D(tm). The formation ofwater-porphyrin associates is a necessary condition for proton exchange between porphyrin and water in the C6D6 medium. It was established that the ability of the studied macroheterocyclic compounds to form associates with water molecules due to the formation of intermolecular hydrogen bonds, as a rule, increases with an increase in the deviation from the planarity of the macrocycle and, consequently, an increase in the steric accessibility of intracyclic NH groups and nitrogen atoms. The obtained data indicate that the K value in the absence of substituents capable of forming hydrogen bonds in the studied macroheterocyclic compounds can be used as an independent criterion for assessing the nonplanarity of the macrocycle in addition to the currently existing structural, spectral and computational methods, as well as to the data obtained in the study of other model reactions.
Keywords: Porphyrins, DOSY spectroscopy, proton exchange, associates, deuteroporphyrin IX, tetraphenylporphine, methylpyropheophorbide a, chlorin e
Образование ассоциатов порфиринов и воды в среде C6D6
Д. В. Белых,а@ А. Л. Столыпко11
аИнститут химии Коми научного центра Уральского отделения Российской академии наук, 167000 Сыктывкар,
Российская Федерация
Сыктывкарский государственный университет им. Питирима Сорокина, 167001 Сыктывкар, Российская Федерация
@Е-таИ: [email protected]
Методом DOSY определены константы (К) равновесия образования-распада ассоциатов молекул ряда порфиринов и хлоринов с молекулой воды в среде С р. Кс и доля связанной с порфирином воды определены экспериментально из зависимостей коэффициентов самодиффузии D от времени диффузии т, D(tт). Показано, что образование ассоциатов «вода-порфирин» является необходимым условием протонного обмена между порфирином и водой в среде Ср. Установлено, что способность исследованных макрогетероциклических соединений к формированию ассоциатов с молекулами воды за счет образования межмолекулярных водородных связей, как правило, повышается с ростом отклонения от планарности макроцикла и, следовательно, стерической доступности внутрициклических групп ЫНи атомов азота. Полученные данные свидетельствуют о том, что величина К при отсутствии у исследуемых макрогетероциклических соединений заместителей, способных образовывать водородные связи, может быть использована в качестве независимого критерия оценки непланарности макроцикла в дополнение к существующим структурным, спектральным и расчетным методам, а также данным изучения других модельных реакций.
Ключевые слова: Порфирины, спектроскопия DOSY, протонный обмен, ассоциаты, дейтеропорфирин IX, тетрафенилпорфин, метилпирофеофорбид а, хлорин e6.
Introduction
The deviation of aromatic macrocycles of porphyrins and their analogs from a planar structure significantly affects the chemical, spectral and other properties of these compounds.[1-6] Therefore, the assessment of the nonplanar-ity of porphyrin macrocycles is of considerable interest.™ To assess the nonplanarity of a porphyrin macrocycle, several mutually complementing groups of methods are used: direct structural methods (X-ray diffraction analysis (XRD) and electron diffraction), spectral methods (fluorescence spectroscopy, resonance Raman spectroscopy, 'H NMR spectroscopy, etc), as well as various computational methods.™ Moreover, to assess the nonplanarity of a macrocycle, data on the reactivity of the coordination center of the macrocycle are widely used (for example, in reactions of complex formation, acid dissociation of intracyclic NH groups, etc.).[1] The formation of an associate of porphyrin with water that involves the formation of intermolecular hydrogen bonds of intracyclic NH groups and nitrogen atoms of the macrocycle can be used as a model reaction to assess the nonplanarity of the porphyrin macrocycle. The strength of the porphyrin-water hydrogen bond should depend on the steric accessibility of the intracyclic NH groups and nitrogen atoms, which, in turn, depends on the degree of distortion of the porphyrin macrocycle (the stronger the deviation from the planar structure, the more sterically accessible the NH groups and nitrogen atoms). Therefore, the values of the equilibrium constants for the formation - decomposition of the porphyrin-water associate can be used for comparison of the nonplanarity of various porphyrins. We have previously shown that proton exchange between water molecules and various natural and synthetic porphyrins in the CDCl3 and C6D6 medium is manifested in DOSY by an increase in the self-diffusion coefficients D of protons of the intracyclic NH group (DNH) in comparison with the C-H protons of the porphyrin molecule (DCH).[7-9] As we found out, the constants of the rate of transfer of the intracyclic proton of the NH group of porphyrin to a water molecule (kNH) and the reverse process (kW) for dimethyl ester of deuteroporphyrin IX in CDCl3[8] and for a number of natural and synthetic porphyrins in C6D6[9] differ from each other, with kW always exceeding kNH. The disparity between the kNH and kW values is explained by the formation of water-porphyrin associates due to intermolecular hydrogen bonds with the participation of intra-cyclic nitrogen atoms of porphyrin, resulting in a decrease in the self-diffusion coefficients of water molecules D ,
what takes place not only due to proton exchange, but also due to the fact that for a fraction of the time water slowly diffuses as part of the associate.17,81 According to the conceptions of the mechanism of proton exchange generalized in the literature,1101 without the formation of a porphyrin-water associate, the implementation of proton exchange is impossible; therefore, the study of the formation of such associates makes it possible to obtain information that is of interest not only from the point of view of assessing the nonplanarity of the macrocycle, but also from the point of view of describing proton exchange as a whole. In this work, using the DOSY method, we have registered the formation of porphyrin-water associates for a number of natural and synthetic porphyrins 1-6 (Scheme 1) and determined the equilibrium constants for these processes.
Materials and Methods
Methylpyropheophorbide a (1), deuteroporphyrin dimethyl ester (5) and meso-tetraphenylporphine (6) were obtained according to [11]. Dibutylamide (2),[12] chlorin e6 methylamide (3),[13] ethanolamide (4)[14] were obtained according the known procedures. The spectral characteristics of the studied compounds correspond to the literature data.[8] The solutions under study were sealed in standard Bruker NMR ampoules with a diameter of 5 mm. All experiments performed with these samples showed that the samples are stable for at least 2 years. The measurements were performed on a Bruker Avance II spectrometer (operating frequency 300 MHz). NMR and DOSY spectra were processed using the MestReNova 14.2.1-27684 program. The concentration ofthe compounds under study in C6D6 was 0.005-0.010 M. The concentration of water in C6D6 was 0.01 M. Parameters of the experiment were as follows: the pulse sequence "double stimulated echo with bipolar gradient pulses" was implemented on a Bruker Avance II spectrometer using the standard dstebpgp3s program with convection compensation; the duration of diffusion D20 varied from 0.025 s to 1 s; the duration of gradient pulses P30 varied from 150 to 1,500 ^s; the accumulation number NS = 64; the number of gradient spectra td (F1) = 16; each spectrum has a sampling frequency of 16k. Time D1 = 5 s (relaxation times for all measured lines of the NMR spectrum did not exceed 1.8 s). The experiments were carried out with temperature stabilization (25 °C) using an air cushion to reduce the influence of external vibrations. The air flow rate in the thermostat was 670 L/h.
Results and Discussion
As noted above, one of the pathways of interaction of porphyrin and water in C6D6 medium is the reversible
X = H(1); X = CON(C4H9)2(2)
NHX
OCHj X = CH3(3); X = CH2CH2OH (4)
Scheme 1.
formation of a porphyrin-water associate according to schematic reaction (1).
H2O + P <-> P---H2O
(1)
In a solution for the reversible association-dissociation reaction described by (1), a dynamic equilibrium is established, so that the amount of the formed water-porphyrin (WP) associates and, accordingly, the proportion of por-phyrin-bound water will be constant over time. The value of the equilibrium concentration of water-porphyrin associates [WP]œ can be determined from the condition of dynamic chemical equilibrium:
= *1-([W„ ]-[( WP }])-([Po ]-[WP])-k 2.[( WP )] = 0,
(2)
where k1 and k2 are the rate constants of the forward and reverse reaction (1), [W0] and [P0] are the equilibrium concentrations of water and porphyrin in the solution, [WP] is the concentration of the water-porphyrin associate in the solution.
Then the expression for the equilibrium constant can be written as follows:
= ^ =
[WP],
k ([ w„ ]- [wpl)-([ p„ ]- [WP],)
(3)
The formation of the porphyrin-water associate should affect the average over the observation time self-diffusion coefficient D of water protons (DW). Since for a fraction of the time the water molecule moves as part of the associate, DW should decrease in comparison with D of water molecules in the absence of porphyrin in the solution, and the more time the water molecule spends as part of the associate (that is, the more stable the associate), the more DW decreases. The change in D can be measured by the DOSY method. However, the detection of the porphyrin-water associate by the DOSY method is complicated by the fact that DW changes not only during the formation of the associate itself, but also due to the participation of water in proton exchange. It is known[7,8,15-17] that the D value of exchanging protons depends on the time of diffusion observation tm (D20). If the change in DW was associated only with the exchange, then at t = 0 Dw should coincide with the value of the diffu-
mW
sion coefficient of free water Dw_ (Dw_ is D for water in CD
WFv WF 6 6
without porphyrin), since the exchange did not yet occur. Nevertheless, a noticeable difference between the values of Dw (0) and Dw_ was observed at t close to zero.[7,8] This
W WF m
difference may be a result of the formation of porphyrin-
water associates. In practice, DOSY measurements at tm = 0 are impossible for technical reasons associated with imperfect parameters of radio frequency and gradient pulses. The minimum possible value for the available equipment was tm ~ 0.02 s. However, the extrapolation of the DW(tm) dependences allows to obtain sufficiently accurate DW(0) values for all measured samples.
Since porphyrin-associated water molecules have a self-diffusion coefficient that coincides with the self-diffusion coefficient Dp for porphyrin, the average observed self-diffusion coefficient of water DW(0) can be expressed by the relation:
dw („) = Dwf-(1 -bw) + Dp • bw
(4)
where Dw_ is the self-diffusion coefficient of water in benzene
WF
in the absence of porphyrin, bw is the fraction of the associated water. Thus, if we know b , we can find , and then from expression (3) we can determine the equilibrium constant Kc. The values of Kc obtained in this way are presented in Table 1. The 'H NMR and DOSY spectra are provided in the Supporting materials.
The porphyrins and chlorins 1-6 studied in this work differ from each other in the degree of nonplanarity ofthe macrocycle both due to the hydrogenation of one of the pyrrole rings (chlorins 1-4 and porphyrins 5, 6) and, for compounds with a chlorin macrocycle, due to the presence (compounds 1 and 2) or the absence (compounds 3 and 4) of an exocycle. Compound 4, in addition, has a hydroxyl group at the periphery of the macrocycle, which should also affect its ability to bind water molecules. In accordance with the Kc values determined in this work (Table 1), the studied compounds can be divided into two groups. The lowest Kc values are observed for porphyrins 5 and 6, what corresponds to a greater planarity of the macrocycle and, accordingly, a lower steric accessibility of intracyclic NH groups and nitrogen atoms of the macrocycle in comparison with chlorins 1-4. Despite the different nature of substitution in macrocycles 5 and 6, the Kc values within the error limits do not differ. In most cases, hydrogenation of one of the pyrrole rings in chlorins 1-4 leads to an increase in their ability to bind water, which is expressed in a significant increase in the Kc value. The exception is dibutylamide 4, the Kc value of which (although it is somewhat higher than that of porphyrins 5 and 6), contrary to expectations, is closer to porphyrins than to chlorins 1-3. This may be due to the influence of peripheral substituents incapable of forming hydrogen bonds on the interaction with water. The reason for this influence is not clear. Apparently, intermolecular interactions in a solution of this compound have a more complex nature. The same reason may be respon-
Table 1. Equilibrium constants (Kc) of porphyrin-water associates formation for compounds 1-6 in C6D6 medium at 25 oC.
Compound Kc (L-mol-1) Compound Kc (L-mol-1)
5 0.32±0.03 1 2.1±0.2
6 0.33±0.03 3 2.2±0.2
2 0.41±0.04 4 4.4±0.4
Scheme 2
Figure 1. Experimental and calculated dependences of the self-diffusion coefficients D (110-9 m2/s) on the diffusion time tm (s)
for compounds 1-6. a - DWF is the self-diffusion coefficient for free water; b - DW is the self-diffusion coefficient for the NMR
line of water; c - DNH is for NMR lines of intracyclic NH groups (both equivalent groups for compounds 5 and 6 and I-NH
for compounds 1-4); d - DNH is for NMR lines of intracyclic groups III-NH (for compounds 1-4); e - Dp is the self-diffusion coefficient
of protons of carbon atoms of deuteroporphyrin.
sible for the fact that very similar Kc values are observed for chlorin 1 that has an exocycle and chlorin 3 that does not have an exocycle. In the case of chlorin 4 that has an OH group capable of forming hydrogen bonds at the periphery of the macrocycle, Kc was significantly higher, which indicates the possibility of binding a water molecule by such peripheral substituents (Scheme 2). A significant increase in Kc in the case of chlorin 4 in comparison with chlorin 3 that is similar in the structure of the macrocycle and peripheral substituents are also consistent with the significantly higher steric accessibility of the hydroxyl group compared to the intracyclic NH groups and nitrogen atoms.
Conclusion
In this work, we used the DOSY method to determine the equilibrium constants (K) of the formation-decomposition of molecular associates of a number of porphyrins
and chlorins with a water molecule in the C D medium.
6 6
Kc and the proportion of porphyrin-associated water were experimentally determined from the dependences of the self-diffusion coefficients D on the diffusion time t , D(tm). We showed that the formation of water-porphyrin associates is a necessary condition for proton exchange between porphyrin and water in the C6D6 medium. We established that the ability of the studied macroheterocyclic compounds to form associates with water molecules due to the formation of intermolecular hydrogen bonds, as a rule, increases with an increase in the deviation from the planar-ity of the macrocycle and, consequently, in the steric accessibility of intracyclic NH groups and nitrogen atoms. Kc for derivatives with a porphyrin macrocycle is always lower than for derivatives with a chlorin macrocycle. The introduction to the periphery of the macrocycle of a hydroxyl group which is not only capable of forming hydrogen bonds but is also sterically more accessible in comparison with intracyclic NH groups and nitrogen atoms results in a sharp increase in K. The data obtained indicate that the K value
cc
in the absence of substituents capable of forming hydrogen bonds in the studied macroheterocyclic compounds can be used as an independent criterion for assessing the nonpla-narity of the macrocycle in addition to the currently existing structural, spectral and computational methods, as well as to the data obtained in the study of other model reactions.
Acknowledgements. Spectral data were obtained using the equipment of the Centre for Collective Usage "Chemistry" of the Institute of Chemistry of the Komi Scientific Centre of the Ural Branch of the Russian Academy of Sciences (Syktyvkar).
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Received 21.09.2021 Accepted 24.10.2021
Макрогетероциклы /Macroheterocycles 2021 14(3) 209-213
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