Molecular Recognition of Imidazole Derivatives by Co(III)-Porphyrins in Phosphate Buffer (pH = 7.4) and Cetylpyridinium Chloride Containing Solutions

Sallam G., Shaban S.Y., Nassar A., El-Khouly M.E.

Here we report the photophysical and sensing properties of the aqueous solution of meso-tetra(N-methyl-4-pyridyl)porphyrin toluene sulfonate (TMPP) for simultaneous detection of toxic metal ions in an aqueous medium by using different physiochemical methods such as UV-vis absorption, steady state and time resolved fluorescence, stopped flow, and cyclic voltammetry. The steady-state absorption and fluorescence spectra in organic solvents (EtOH, DMSO, DMF, MeOH and ACN) showed the formation of monomer form (λmaxabs = 426 nm and λmaxflu = 654 and 715 nm). In THF and water, different spectral features were recorded suggested the formation of aggregated forms in both solvents. The formation of aggregated form in water was confirmed by recording the remarkable fluorescence quenching of the singlet excited TMPP with increasing the concentrations of TMPP. In cationic micelles (CTAB), both the absorption and fluorescence spectra were significantly decreased with increasing the concentrations of CTAB with a break at CMC value at 6.0 × 10-5 M. In an anionic micelle (SDS), the CMC value was found to be 1.0 × 10-4 M. Upon interacting with different metal ions, the absorption and fluorescence spectra of TMPP showed different features depending on the metal ions. While the optical studies of TMPP showed no significant interaction in the presence of Mn+2, Co+2, Ba2+, and Ni+2, TMPP showed that it can function as a single optical chemical sensor for the toxic metal ions in water, particularly Hg+2, Pb+2, Cu+2, and Cd+2 ions.

Lazovskiy D.A., Mamardashvili G.M., Khodov I.A., Mamardashvili N.Z.

This paper reports the results of the synthesis and identification of water soluble trans-diaxial complexes of Sn(IV)-5,10,15,20-tetra-(4-sulfophenyl)porphyrin with fluorescein, in which the organic ligands are bound to the tin cation of the tetrapyrrolic macrocycle via a carboxyl (triad I) or a hydroxyl (triad II) group. The structures of triads (I, II) were confirmed by the methods of one- and two-dimensional NMR and quantum-chemical modeling. A spectrophotometric method was used to study the spectral, acidic and fluorescence properties of the synthesized compounds. The paper also discusses the possible mechanisms of protolytic and tautomeric equilibria in the processes involving fluorescein ligands in the axial complexes with hydrophilic Sn(IV)porphyrin. It is found that the fractional distribution of the triads with the lactone, quinoid, and zwitterionic forms of fluorescein axial ligands depends on the medium acidity, exhibiting high pH sensitivity in the ranges where this substance and its derivatives in the free state do not exhibit fluorescence. As a result, the ability of the porphyrin-fluorescein triads to determine water acidity can be used to develop an effective method of detecting pH-dependent biological processes and environmental pollution. This method will facilitate the production of new fluorescent sensors for biomedical purposes (drug delivery triggered by pH changes or oxygen distribution in tissues) and engineering applications (wastewater detection).

Mamardashvili G.M., Kaigorodova E.Y., Simonova O.R., Lazovskiy D.A., Mamardashvili N.Z.

Processes of anionic Sn(IV)-tetra(4-sulfonatophenyl)porphyrin axial complexes with three different ligands (hydroxyl, methoxidol and tyrosine) inclusion in an oppositely charged surfactant in a phosphate buffer at 25 °C were studied. It was shown how the association and localization of the porphyrins into spherical cetyltrimethylammonium bromide micelles affect the aggregation, micelle formation, fluorescent properties and photochemical stability of the systems formed depending on the nature of the Sn(IV)-porphyrin axial ligands. The results obtained determine conditions for quenching or enhancement the fluorescence of the hydrophilic Sn(IV)-porphyrin complexes while reducing the possibility of their photochemical destruction and can be useful in the design of new types of photosensitizers for PDT. • Processes of anionic Sn-porphyrins interaction with cationic surfactant were studied. • Porphyrin localization into micelle affects fluorescent properties and photochemical stability. • Systems with improved fluorescence and photo-stability were designed.

Mondal S., Banerjee A., Das B.

A comprehensive investigation on the interactions between equine heart hemoglobin and different surface active agents including ionic liquid surfactants (ILs) was performed in aqueous buffer (pH = 7.4) by ultraviolet-visible and fluorescence spectroscopic techniques coupled with tensiometry. The surface active agents include a cationic surfactant cetyltrimethylammonium bromide (CTAB), two cationic ILs 1-hexadecyl-3-methylimidazolium chloride (C16MeImCl), 1-butyl-3-methylimidazolium octyl sulfate (C4MeImOS), three anionic surfactants sodium N-dodecanoyl sarcosinate (SDDS), sodium dodecylbenzene sulfonate (SDBS), sodium cholate (NaC), and a non-ionic surfactant N-decanoyl-N-methylglucamine (Mega 10). In particular, surfactant-induced conversion of the iron coordination and spin states of hemoglobin was monitored by the shifts of the Soret peak. Fluorescence studies indicated exposure of the tryptophan and tyrosine residues of hemoglobin to polar environment when surface active agents were introduced, the relative contributions of these amino acids to the fluorescence intensity being different for different surfactants. Hemoglobin was found to be unfolded in surfactant solutions. Unfolding of hemoglobin was found to be more pronounced in presence of ionic surfactants than in presence of the non-ionic one.

Maaskant R.V., Polanco E.A., van Lier R.C., Roelfes G.

Here, we report that the combination of cationic iron porphyrins with sodium dodecyl sulphate (SDS) gives rise to efficient micellar catalysis of cyclopropanation reactions of styrene derivatives, using diazoacetates as carbene precursors.

Allen S.A., Datta S., Sandoval J., Tomilov A., Sears T., Woolard K., Angelastro J.M., Cortopassi G.A.

AMP-activated protein kinase (AMPK) is a eukaryotic energy sensor and protector from mitochondrial/energetic stress that is also a therapeutic target for cancer and metabolic disease. Metformin is an AMPK inducer that has been used in cancer therapeutic trials. Through screening we isolated cetylpyridinium chloride (CPC), a drug known to dose-dependently inhibit mitochondrial complex 1, as a potent and dose-dependent AMPK stimulator. Mitochondrial biogenesis and bioenergetics changes have also been implicated in glioblastoma, which is the most aggressive form of brain tumors. Cetylpyridinium chloride has been administered in humans as a safe drug-disinfectant for several decades, and we report here that under in vitro conditions, cetylpyridinium chloride kills glioblastoma cells in a dose dependent manner at a higher efficacy compared to current standard of care drug, temozolomide.

Mamardashvili G.M., Kaigorodova E.Y., Khodov I.A., Scheblykin I., Mamardashvili N.Z., Koifman O.I.

Mamardashvili G.M., Maltceva O.V., Lazovskiy D.A., Khodov I.A., Borovkov V., Mamardashvili N.Z., Koifman O.I.

Supramolecular triads consisting of hydrophilic Sn(IV)-tetra(4-sulfophenyl)-porphyrin and two axial guests such as propylphenol, tyrosine, and 2-(2-hydroxyphenyl)-benzoxazole were synthesized. The structures of synthesized complexes were identified by experimental spectroscopic and quantum-chemical simulation methods, and their fluorescent properties were studied in various viscosity media (mixed phosphate buffer-glycerin solvents of different composition). The effect of axial ligand structure on the fluorescent properties of these triads (due to the hydrogen bonding or π-π stacking between the components of «host-guest» systems) is discussed. The potential use of synthesized complexes as environmental probes of local viscosity is proposed.

Mondal B., Saha S., Borah D., Mazumdar R., Mondal B.

The reaction of a cobalt porphyrin complex, [(F8TPP)Co], 1 {F8TPP = 5,10,15,20- tetrakis(2,6-difluorophenyl)porphyrinate dianion} in dichloromethane with nitric oxide (NO) led to the nitrosyl complex, [(F8TPP)Co(NO)], 2. Spectroscopic studies and structural characterization revealed it as a bent nitrosyl of {CoNO}8 description. It was stable in the presence of dioxygen. However, it reacts with H2O2 in acetonitrile (or THF) solution at -40 °C (or -80 °C) to result in the corresponding Co(III)-nitrate complex, [(F8TPP)Co(NO3)], 3. The reaction presumably proceeds via the formation of a Co-peroxynitrite intermediate. X-Band electron paramagnetic resonance and electrospray ionization-mass spectroscopic studies suggest the intermediate formation of the [(porphyrin)Co(III)-O•] radical, which in turn supports the generation of the corresponding Co(IV)-oxo species during the reaction. This is in accord with the homolytic cleavage of the O-O bond in heme-peroxynitrite proposed in the nitric oxide dioxygenases activity. In addition, the characteristic peroxynitrite-induced phenol ring reaction was also observed.

Mamardashvili G., Kaigorodova E., Simonova O., Mamardashvili N.

By spectrophotometric titration, 1H NMR and cyclic voltammetry the processes of Co(II)-5,10,15,20-tetraphenylporphyrin, Co(II)-5,10,15,20-tetraphenyl-2,3,7,8,12,13,17,18-tetrabenzoporphyrin, Co(II)...

Kaigorodova E.Y., Mamardashvili G.M., Mamardashvili N.Z.

The substitutions of water molecules in the bisaqua axial complex of carboxy-substituted Co(III)-tetraphenylporphyrin by drug molecules based on amines and nitrogen-containing heterocycles are studied. The strongest bonded Co(III)-porphyrin complexes are formed with imidazole and pyridine derivatives. Depending on the nature and positions of functional groups in the heterocyclic moiety, imidazole- and pyridine- containing compounds can form either mono- or bis-axial complexes with Co(III) porphyrinate, these complexes having various stabilities. Aniline and quinuclidine drugs were found to react with Co(III) porphyrinate in aqueous media to produce only unstable monoaxial complexes.

Mamardashvili G.M., Chizhova N.V., Kaigorodova E.Y., Mamardashvili N.Z.

Comparison of tetrabenzoporphyrin complexation reactions and transmetalation of cadmium(II) tetrabenzoporphyrinate with cobalt(II) acetate and chloride in dimethylformamide (DMF) has been carried out Cobalt(III) tetrabenzoporphyrinate has been prepared and identified. Acido ligands displacement in Co(III) tetrabenzoporphyrinate by pyridine, imidazole, and quinuclidine molecules has been studied.

Maltceva O., Mamardashvili G., Khodov I., Lazovskiy D., Khodova V., Krest’yaninov M., Mamardashvili N., Dehaen W.

Abstract By means of spectrophotometric titration and 1H NMR spectroscopy, the selective binding ability of the Zn-5,15-bis-(2,6-dodecyloxyphenyl)porphyrin towards nitrogen containing organic molecules of various nature has been studied. It has been found that the presence of long alkoxy substituents at the ortho-positions of the Zn-porphyrin phenyl rings prevents the axial coordination of tertiary amines and, conversely, creates favourable conditions for binding of a primary diamine due to the presence of additional binding sites, namely the oxygen atoms of the ortho–ortho′- dodecyloxy substituents of the meso phenyl groups. The formation of stable complexes with multiple binding sites has been confirmed by DFT quantum chemical calculations and two-dimensional NMR experiments.

Biedermann F., Schneider H.

On the basis of many literature measurements, a critical overview is given on essential noncovalent interactions in synthetic supramolecular complexes, accompanied by analyses with selected proteins. The methods, which can be applied to derive binding increments for single noncovalent interactions, start with the evaluation of consistency and additivity with a sufficiently large number of different host-guest complexes by applying linear free energy relations. Other strategies involve the use of double mutant cycles, of molecular balances, of dynamic combinatorial libraries, and of crystal structures. Promises and limitations of these strategies are discussed. Most of the analyses stem from solution studies, but a few also from gas phase. The empirically derived interactions are then presented on the basis of selected complexes with respect to ion pairing, hydrogen bonding, electrostatic contributions, halogen bonding, π-π-stacking, dispersive forces, cation-π and anion-π interactions, and contributions from the hydrophobic effect. Cooperativity in host-guest complexes as well as in self-assembly, and entropy factors are briefly highlighted. Tables with typical values for single noncovalent free energies and polarity parameters are in the Supporting Information.

Khodov I.A., Kiselev M.G., Efimov S.V., Klochkov V.V.

Kaigorodova E.Y., Mamardashvili G.M., Mamardashvili N.Z.

Mamardashvili G., Kaigorodova E., Solomonova N., Mamardashvili N.

Kaigorodova E.Y., Mamardashvili G.M., Kurochkin I.Y., Mamardashvili N.Z.

The processes of supramolecular self-assembly of Co(III)-meso-tetra-(4-trimethylammoniophenyl)porphyrin (CoP) and bis-(4-(1-imidazolyl)-phenol)-Sn(IV)-meso-tetra(4-sulfophenyl)porphyrin (SnP) were studied using electronic, steady-state and time-resolved fluorescence, one- and two-dimensional NMR spectroscopy in aqueous media. The main product of such interaction at a 2:1 M ratio of Co and Sn porphyrinates was found to be supramolecular porphyrin trimer CoP–SnP–CoP formed due to donor-acceptor, hydrogen and electrostatic interactions. The distinctive features of the resulting trimer are: significant distortion of the spatial structure of the Co-porphyrin fragments and strong quenching of the Sn-porphyrin macrocycles fluorescence (by 70 %). The distortion of the spatial structure of Co porphyrinates is in good agreement with the quantum chemical calculations as well as with the electronic and NMR spectroscopy data. Adding surfactants – both anionic (Cetyltrimethylammonium bromide - CTAB) and cationic (Sodium dodecyl sulfate - SDS) – even at concentrations below the critical micelle concentration (CMC) leads to the supramolecular trimer destruction. In solutions of ionic surfactants, supramolecular trimer destruction is caused by the interaction of either the peripheral macrocycles of the trimer (CoP) with SDS micelles (premicellar aggregates) or the central macrocycle (SnP) with CTAB micelles (premicellar aggregates). This process is prolonged and the rate of trimer destruction depends on the surfactant concentration. The sizes of the CTAB and SDS micelles solubilized with porphyrin molecules were established by dynamic light scattering. In general, surfactant additions lead to an increase in the SnP fluorescence at least due to the destruction of the supramolecular self-assembly, as well as due to the changes in the state of its microenvironment.

Mamardashvili G.M., Kaigorodova E.Y., Khodov I.A., Mamardashvili N.Z.

The study explores the interactions between 5,10,15,20-tetra(N-methylpyridyl)porphyrin (H2P) and sodium dodecyl sulfate (SDS) at concentrations below the critical micelle concentration (CMC) in aqueous solutions employing spectrophotometric and fluorescence methods. The composition and structure of the complexes involved in the association of H2P with premicellar SDS aggregates of varying compositions denoted as [H2P-5·SDS], [H2P-10·SDS] and [H2P-20·SDS] were characterized using mass spectrometry, DOSY, and 1D NOESY techniques. Possible reasons for the decrease in the intensity of absorption and emission of porphyrin in micellar aggregates of SDS compared to porphyrin in an aqueous environment are analyzed. The research has revealed that SDS can act as both a catalyst and an inhibitor, depending on its concentration in the reaction of complexation of H2P with metal cations (Co2+). The spectrophotometric approach examined interaction processes between 5,10,15,20-tetra(N-methylpyridyl)porphyrinate Co(III) and premicellar SDS aggregates, which proceed similarly to the processes with the porphyrin ligand. The study demonstrated the impact of premicellar aggregates on the binding capacity of Co(III) porphyrinate with electron-donating molecules using imidazole as an illustrative example.

Mamardashvili G.M., Kaigorodova E.Y., Mamardashvili N.Z., Koifman O.I.

Zvezdina S.V., Chizhova N.V., Mamardashvili N.Z.

Reactions of complex formation of 5,10,15,20-tetra-(2,6-dichlorophenyl)porphyrin, 5,10,15,20-tetra-(2,6-difluorophenyl)porphyrin and metal exchange of their cadmium complexes with manganese chloride(II) in dimethylformamide were investigated. ortho -Substituted manganese complexes were synthesized by prolonged refluxing of the corresponding porphyrins with an excess of MnCl2 in dimethylformamide. Using the metal exchange reaction of Cd(II)-5,10,15,20-tetra-(2,6-dichlorophenyl)porphyrin and Cd(II)-5,10,15,20-tetra-(2,6-difluorophenyl) porphyrin, the corresponding Mn(III)-tetraphenylporphyrins were obtained. On the contrary, the coordination reactions of porphyrins substituted at the pyrrole and phenyl rings with manganese chloride in dimethylformamide proceed under mild conditions with the formation of complexes Mn(II)-2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetra-(2,6-dichlorophenyl)porphyrin [the compound oxidizes in air to a mixture of Mn(II) and Mn(III)-porphyrins] and Mn(II)-2,3,7,8,12,13,17,18-octachloro-5,10,15,20-tetra-(2,6-difluorophenyl)porphyrin. The synthesized compounds were identified using UV-Vis, 1H NMR spectroscopy and mass-spectrometry. Metal exchange reaction of ortho -substituted Cd(II)-porphyrins and complex formation of 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetra-(2,6-dichlorophenyl)porphyrin with manganese chloride in dimethylformamide were studied by the spectrophotometric method. The kinetic parameters of the reactions were calculated. A strong effect of β- and ortho -substitution on the reactions of complex formation and metal exchange of the studied compounds was found.

Zvezdina S.V., Chizhova N.V., Mamardashvili N.Z.

The complexation of 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin and 5,10,15,20-tetrakis(2,6-difluorophenyl)porphyrin and metal exchange reactions of their cadmium complexes with manganese(II) chloride in DMF were studied with the goal of finding optimal conditions for the synthesis of manganese(II) and manganese(III) complexes with tetrapyrrole macrocyclic compounds. ortho-Substituted manganese com­plexes were synthesized by prolonged heating of the corresponding porphyrins with excess MnCl2 in boiling DMF. Metal exchange reactions of cadmium(II) 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin and cadmium(II) 5,10,15,20-tetrakis(2,6-difluorophenyl)porphyrin with MnCl2 in DMF produced the corresponding manganese(III) tetraphenylporphyrins. In contrast, the complexation of tetraphenylporphyrins substituted at both pyrrole and phenyl rings with manganese(II) chloride in DMF under mild conditions afforded manga­nese(II) 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin, which was oxidized to a mixture of manganese(II) and manganese(III) porphyrins on exposure to air, and manganese(II) 2,3,7,8,12,13,17,18-octachloro-5,10,15,20-tetrakis(2,6-difluorophenyl)porphyrin. The synthesized compounds were identified by electronic absorption spectroscopy, 1H NMR, and mass spectrometry. The metal exchange reactions of ortho-substituted cadmium(II) tetraphenylporphyrins and the complexation of 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin with manganese(II) chloride in DMF were studied by spectrophotometry, and their kinetic and activation parameters were determined. A significant effect of β- and ortho-substitution on the complexation and metal exchange reactions was revealed.

Mamardashvili G., Kaigorodova E., Lebedev I., Mamardashvili N.

The methods of 1H NMR, spectrophotometric titration, mass spectrometry and elemental analysis are applied to determine the selective binding ability of Co(III)- and Zn(II)-coproporphyrins I towards a series of imidazole-based drug molecules with a wide spectrum of pharmacological activity (metronidazole, histamine, histidine, tinidazole, mercazolil, and pilocarpine) in phosphate buffer (pH 7.4) simulating the blood plasma environment. It is shown that in aqueous buffer media, Co(III)-coproporphyrin I, unlike Zn(II)-coproporphyrin I, binds two imidazole derivatives, and the stability of mono-axial Co-coproporphyrin imidazole complexes is two to three orders of magnitude higher than that of similar complexes of Zn-coproporphyrin I. The studied porphyrinates are found to have the highest binding ability to histamine and histidine due to the formation of two additional hydrogen bonds between the carboxyl groups of the porphyrinate side chains and the binding sites of the ligands in the case of histidine and a hydrogen bond between the amino group of the ligand and the carbonyl oxygen atom of the carboxyl group of the porphyrinate in the case of histamine. The structures of the resulting complexes are optimized by DFT quantum chemical calculations. The results of these studies may be of use in the design of biosensors, including those for the detection, control and verification of various veterinary drug residues in human food samples.

Zvezdina S.V., Chizhova N.V., Mamardashvili N.Z., Koifman O.I.

Mamardashvili G.M., Yu. Kaigorodova E., Lebedev I.S., Khodov I.A., Mamardashvili N.Z.

• Hydrophilic Co-porphyrins self-assembly with bidentate ligands in water were studied. • Encapsulation of the supramolecular assembles into micelles were investigated. • Supramolecular porphyrin based assembles with preprogrammed lifetime were designed. The processes of hydrophilic Co(III)-tetra(4-sulfonatophenyl)porphyrin supramolecular assembly with 4,4-bipyridyl in aqueous buffer media have been studied by UV–vis, 1D and 2D 1 H NMR-spectroscopy. In the case of 1,4-diazabicyclo[2.2.2]octane, pyrazine and piperazine in aqueous solutions, no assembly was observed. Interactions of the hydrophilic Co(III)-tetraarylporphyrin with ionic micelles (cationic surfactants with different alkyl tail lengths) in buffer media were investigated. These studies were performed by the UV–vis, 1 D NOESY-spectroscopy and dynamic lightscattering (DLS) methods. The metalloporphyrins were incorporated into the hydrophobic part of micelles, which led to Co(III) reduction to Co(II) in the Co-porphyrinate composition. The rate of Co(III) reduction accompanied by detachment of additional ligands coordinated on Co(III)-porphyrins or disruption of supramolecular dimers and depends on the surfactant concentration and nature. The results obtained indicate the possibility of creating of supramolecular porphyrin-based assembles with the preprogrammed lifetime (from several hours to several days) and could be used in the creation of host – guest systems for recognition, selective binding and prolonged release of bioactive substrates as the means in the designing of biomimetic systems with effective binding affinities to heterocycles, DNA base pairs and RNA.

Kaigorodova E.Y., Mamardashvili G.M., Mamardashvili N.Z.

The processes of hydrophilic Co(III)-tetra(4-sulfonatophenyl)porphyrin supramolecular assembly with 4,4-bipyridyl in aqueous buffer media have been studied by UV-vis, 1D and 2D 1H NMR-spectroscopy. In the case of 1,4-diazabicyclo[2.2.2]octane, pyrazine and piperazine in aqueous solutions, no assembly was observed. Interactions of the hydrophilic Co(III)-tetraarylporphyrin with ionic micelles (cationic surfactants with different alkyl tail lengths) in buffer media were investigated. These studies were performed by the UV-vis, 1D NOESY-spectroscopy and dynamic lightscattering (DLS) methods. The metalloporphyrins were incorporated into the hydrophobic part of micelles, which led to Co(III) reduction to Co(II) in the Co-porphyrinate composition. The rate of Co(III) reduction accompanied by detachment of additional ligands coordinated on Co(III)-porphyrins or disruption of supramolecular dimers and depends on the surfactant concentration and nature. The results obtained indicate the possibility of creating supramolecular porphyrin-based assemblies with the preprogrammed lifetime (from several hours to several days) and could be used in the creation of host-guest systems for recognition, selective binding and the prolonged release of bioactive substrates as the means in the designing of biomimetic systems with effective binding affinities to heterocycles, DNA base pairs and RNA.

Mamardashvili G., Mamardashvili N., Koifman O.

Molecular recognition of host/guest molecules represents the basis of many biological processes and phenomena. Enzymatic catalysis and inhibition, immunological response, reproduction of genetic information, biological regulatory functions, the effects of drugs, and ion transfer—all these processes include the stage of structure recognition during complexation. The goal of this review is to solicit and publish the latest advances in the design and sensing and binding abilities of porphyrin-based heterotopic receptors with well-defined geometries, the recognition ability of which is realized due to ionic, H-bridge, charge transfer, hydrophobic, and hydrophilic interactions. The dissection of the considered low-energy processes at the molecular scale expands our capabilities in the development of effective systems for controlled recognition, selective delivery, and prolonged release of substrates of different natures (including drugs) to their sites of functioning.