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Photophysical properties of meso-tetrakis(4-N-methylpyridiniumyl)porphyrin (TMpyP4) and its metallocomplexes M(II)TMpyP4 (M = Zn, Cu, Ni, Co) bound to natural DNA and synthetic poly-, oligo- and mononucleotides are considered with a primary emphasis placed upon intermolecular interaction of the photoexcited porphyrins with the nearest environment. Quenching of the fluorescent S₁ (but not triplet T₁) state due to guanine to porphyrin electron transfer is observed for TMpyP4 intercalated between GC base pairs of the double-strand helixes, whereas in the case of TMpyP4 complexed with guanosine monophosphate (GMP) both S₁ and T₁ states of the porphyrin are quenched. Furthermore, a dependence of the efficiency of TMpyP4 triplet state quenching by the dissolved molecular oxygen from air on the porphyrin localization enables one to readily distinguish porphyrin groove binding mode from intercalation. Excited states of the TMpyP4 complexes with transition metals, in spite of their very short lifetimes, also interact with nucleic acid components by means of an axial ligand binding/release to/from the metal. A possible structure of the five-coordinate excited complex (“exciplex”) formed in case of CuTMpyP4 groove binding to some single- and double-strand polynucleotides is discussed.

In this review, porphyrins bearing quaternary azaaromatic moieties are described as follows: firstly those with useful physicochemical properties, then, species showing biological activities and finally, porphyrins bound with fullerenes and with cyclodextrins.

Binding properties of two water-soluble porphyrins, manganese(III) 5-(1-(4-carboxybutyl)pyridinium-4-yl) 10,15,20-tris(1-methylpyridinium-4-yl)porphyrin (Mn(III)5-CBPyP) and manganese(III) 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (Mn(III)TMPyP), in the presence of various concentration of calf thymus DNA (ct-DNA), has been studied in 7.5 mM phosphate buffer, pH = 7.2 and at various temperatures by UV-vis absorption, resonance light scattering (RLS) and fluorescence spectroscopy and viscosity measurement. Optical absorption and RLS measurements have demonstrated three different species of both porphyrins form in DNA solution. The thermodynamic parameters were calculated by van't Hoff equation at various temperatures. The values of -4.89 kJ.mol^-1 and +65.98 J.mol^-1.K^-1 for Mn(III)5-CBPyP and -14.92 kJ.mol^-1 and +15.46 J mol^-1.K^-1 for TMPyP were estimated for enthalpy and entropy changes of interaction, respectively. The data indicate that the process is exothermic and enthalpy- and entropy-driven, suggesting that electrostatic forces play a considerable role in the interaction process. The binding of both porphyins to DNA quenches fluorescence emission of ethidium bromide (EB) and the quenching process obeys linear Stern-Volmer relationship, indicating the quenching of electron transfer of EB from its binding sites by these porphyrins. The results of using these techniques indicate the external mode of binding for both porphyrins and a higher binding affinity of Mn(III)5-CBPyP with respect to Mn(III)TMPyP.

In the present study, the activity of the new water-soluble cationic meso-tetra(4-N-oxyethylpyridyl)porphyrin and its Zn, Ag and Co metal derivatives as anti-tumor agents was explored. The tumor was induced by 7,12-dimethylbenz[a]antracene (DMBA) on rats of Wistar strain. The levels of DNA damage induced by porphyrins T4OEPyP, AgT4OEPyP, ZnT4OEPyP and CoT4OEPyP in tumor tissue were analyzed. Thermodynamic parameters of DNA were investigated by thermal melting method and differential scanning microcalorimetry to understand the differences in DNA structure of three types of rat: normal, dieseased with tumor, and treated by porphyrins. Agarose gel electrophoresis method was used to detect porphyrin-induced apoptosis or necroses. Based on the data obtained, we concluded that the investigated ZnTOEPyP and AgTOEPyP porphyrins have more anti-tumor activity than CoTOEPyP and TOEPyP.

Recent developments in DNA-mediated nanostructuring have paved the way for the development of novel reaction centers. As part of a project focused on nanostructured reaction centers for reactions catalyzed by porphyrins, we have developed a solid-phase synthesis of tetrakis(p-hydroxyphenyl)porphyrin-oligonucleotide hybrids. In these hybrids, up to four nucleic acid chains are linked to the phenolic substituents of the porphyrin via phosphodiester linkages. A representative hybrid with one oligonucleotide chain of the sequence TTAA was found to survive light irradiation under aerobic conditions for 2 h with less than 35% oxidation of the DNA chain. An assay measuring the diastereo- and enantioselectivity of the photosensitized ene reaction of mesitylol with singlet oxygen was set up that provides diastereomeric ratios via NMR of aliquots of the reaction solution. Enantiomers were separated gas chromatographically on a chiral stationary phase and were assigned based on the product distribution obtained with an enantiomerically enriched starting material. Our results are a starting point for the exploration of nanostructured reaction media based on DNA and porphyrins.

A porphycene with a hydroxyethyl side chain was coupled to the 3′-terminus of an oligodeoxynucleotide via solid-phase synthesis. The resulting porphycene-DNA hybrid binds to a complementary region of a DNA target strand with greater affinity than the unmodified control oligonucleotide, resulting in an increase of the UV-melting point of 12.7 °C. Duplex formation is accompanied by an increase in porphycene fluorescence at 640 nm by 18%. When a tetrakis(p-hydroxyphenyl)porphyrin appended to the 5′-terminus of another DNA-strand is brought into close proximity of the porphycene by hybridizing it to the downstream-region of the template strand, 94% of the porphycene fluorescence is quenched. By quenching each others fluorescence to different degrees, porphycene and porphyrin, together, report on local DNA structure in a fashion reminiscent of that of molecular beacons. The introduction of porphycenes and the porphycene-porphyrin "two hybrid system'' to DNA-based structuring may open up new avenues to designed functional materials.

The binding mode of a porphyrin dimer to double stranded native DNA was investigated in this study using normal electric absorption, circular dichroism (CD) and linear dichroism (LD) spectroscopies. At the time of mixing, the spectral properties of the porphyrin dimer upon its association with DNA were characterized by hypochromism and a red shift in the absorption spectrum and by complicated CD and negative LD in the Soret region. As time elapsed, the CD spectrum became a negative single band and the negative LD signal increased. These spectral changes suggested that the majority of both porphyrin moieties of the dimer intercalated between the DNA base-pairs. The changes in the spectral characteristics of the DNA bound porphyrin-dimer were similar when the minor groove of DNA was saturated by 4′,6-diamidino-2-phenylindole (DAPI), which is well-known minor groove binding molecule. The spectral properties of DAPI, which can be summarized by a large positive induced CD in the DAPI absorption region (300~400 nm) and wavelength-independent positive reduced LD, remained intact when the porphyrin dimer was present. These observations indicated that both DAPI and porphyrin bind to DNA simultaneously, and furthermore, the bis-intercalation of the porphyrin dimer occurs in the major groove.

One of the porphyrin moieties of the porphyrin dimer intercalates rapidly between the DNA base-pairs, followed by the slow intercalation of the other. The slow intercalation of the second porphyrin moiety of porphyrin dimer to poly[d(G-C)₂] was investigated by normal absorption and circular dichroism spectroscopy. The change in absorbance in the Soret band of porphyrin upon association with poly[d(G-C)₂] can be best elucidated by the combination of the two single exponential curves, suggesting the intercalation occurred via two independent first order reactions. Activation energies of these two first order reactions were calculated to be 0.37 kcal/mol and 3.19 kcal/mol, respectively. The intercalation associated with lower activation energy can be assigned to the intercalation of second porphyrin moiety to 5′CG3′ site while that with higher activation energy to 5′GC3′ intercalation site. Increasing the flexibility of poly[d(G-C)₂] by adding Na⁺ ion resulted in an enhancement of the reaction rate for both steps in an exponential manner.

The influence of water soluble cationic meso-tetra(4N-hydroxyethyl)pyridyl porphyrin (H₂THOEtPyP4) and it's metal complexes with Ni(II), Cu(II), Co(II) and Zn(II) on hydrodynamic and spectral behavior of DNA solutions has been studied by viscometry and UV-vis absorption methods. It was shown that the presence of planar porphyrins, such as H₂THOEtPyP4, NiTHOEtPyP4 and CuTHOEtPyP4 leads to an increase in viscosity at relatively small concentrations, and then decreases to stable values. Such behavior corresponds to intercalation of these porphyrins in DNA structure, which results in a decrease of helical twist and lengthening of the DNA molecule. In the case of porphyrins with axial ligands, such as ZnTHOEtPyP4 and CoTHOEtPyP4, the relative viscosity decreases, which is explained by self-stacking of these porphyrins on DNA surface. Calculation and interpretation of binding parameters (K_b and n) demonstrated good agreement of viscometric and spectrophotometric measurements.

Ternary complexes composed of protoheme (heme(Fe³⁺)) or 13,17-bis(2-carboxylatoethyl)-3,7-diethyl-12,18-trimethyl-2,8-ditrifluoromethylporphyrinatoiron(III) (2,8-DPF(Fe³⁺)), a parallel G-quadruplex DNA formed from a single repeat sequence of the human telomere, d(TTAGGG), and imidazole (Im), in a ratio of 1:1:1, were prepared and their structures were characterized using optical, circular dichroism, and NMR spectroscopies. The study revealed that heme(Fe³⁺) and 2,8-DPF(Fe³⁺) stack onto the 3′-terminal G-quartet of the G-quadruplex DNA, ~0.4 nm apart, and that Im is coordinated to the Fe atom on the side of the heme opposite to the G-quartet in the complex. The stacking of the pseudo-C₂ symmetric heme(Fe³⁺) onto the C₄ symmetric G-quartet in the complex resulted in the formation of two isomers with heme orientations differing by 180° about the pseudo-C₂ axis, with respect to the DNA. The Im affinity of the 2,8-DPF(Fe³⁺)-DNA complex was higher by a factor of ~2 than that of the heme(Fe³⁺)-DNA one, which is possibly due to the stronger ligand-to-metal π donation in the 2,8-DPF(Fe³⁺) as a result of a decrease in the electron density of the heme Fe atom caused by substitution of the two strongly electron-withdrawing trifluoromethyl groups.

Guanine-rich single-stranded nucleic acids self-assemble into G-quadruplex nanostructures (predominately in the presence of K⁺-ions). Metalloporphyrins bind to the G-quadruplex nanostructures to form supramolecular assemblies exhibiting unique catalytic, electrocatalytic and photophysical properties. This paper addresses the advances in the characterization and the implementation of the metalloporphyrin/G-quadruplexes complexes for various applications. Out of the different complexes, the most extensively studied complexes are the hemin/G-quadruplex horseradish peroxidase-mimicking DNAzyme and the Zn(II)-protoporphyrin IX-functionalized G-quadruplex. Specifically, the hemin/G-quadruplex was found to act as a catalyst for driving different chemical transformations that mimic the native horseradish peroxidase enzyme, and, also, to function as an electrocatalyst for the reduction of H₂O₂. Also, the hemin/G-quadruplex stimulates interesting photophysical and photocatalytic processes such as the electron-transfer quenching of semiconductor quantum dots or the chemiluminescence resonance energy transfer to semiconductor quantum dots. Alternatively, Zn(II)-protoporphyrin IX associated with G-quadruplexes exhibit intensified fluorescence properties. Beyond the straight forward application of the metalloporphyrin/G-quadruplexes as catalysts that stimulate different chemical transformations, the specific catalytic, electrocatalytic and photocatalytic functions of hemin/G-quadruplexes are heavily implemented to develop sophisticated colorimetric, electrochemical, and optical sensing platforms. Also, the unique fluorescence properties of Zn(II)-protoporphyrin IX-functionalized G-quadruplexes are applied to develop fluorescence sensing platforms. The article exemplifies different sensing assays for analyzing DNA, ligand-aptamer complexes and telomerase activity using the metalloporphyrins/G-quadruplexes as transducing labels. Also, the use of the hemin/G-quadruplex as a probe to follow the operations of DNA machines is discussed.

Two novel water-soluble porphyrin-phosphonate conjugates were synthesized and characterized. Although both conjugates showed significant potential in photodynamic therapy, the variety of their structure induced the obvious differences in the binding manner with calf thymus DNA, the cytotoxicity and the cellular sublocalization.

The first oxidative cleavage of DNA by manganese $N$-confused porphyrin [chloro(2-aza-2-methyl-5,10,15,20-tetrakis($p$-chlorophenyl)-21-carbaporphyrin)manganese(III), 1] using H₂O₂ as oxidant agent and its magnetic, calf thymus DNA(ct-DNA)- and human serum albumin (HSA) binding properties were investigated. The magnitude of the axial (D) zero-field splitting for the mononuclear Mn(III) center in 1 was determined to be approximately 2.71 cm${}^{-1}$ by paramagnetic susceptibility measurements. The DNA- and HSA binding experimental results showed that 1 bound to ct-DNA via an outside groove binding mode and the hydrophobic cavity located in subdomain IIA of HSA with the binding constant of 4.144 × 10⁵ M${}^{-1}$ and $\sim$ 10⁶ M${}^{-1}$, respectively. Thermodynamic parameters revealed that both DNA- and HSA binding were spontaneous process. The main driven forces were the hydrogen bond and van der Waals for the former, but hydrophobic interaction for the latter, which were further confirmed by molecular docking modeling. Manganese $N$-confused porphyrin 1 could cleave the supercoiled plasmid DNA efficiently in the presence of hydrogen peroxide. Hydroxyl radical (${}^{•}$OH) was found the active species for oxidative damage of DNA.

The influence of porphyrin molecules configuration on their ability to affect on DNA structure were investigated for water-soluble cationic meso-tetra-(3N-hydroxyethylpyridyl) porphyrin (H₂THOEtPyP3) and its metal complexes with Cu, Ni, Co, Zn using viscometry and UV-vis absorption spectroscopy. A comparative analysis was performed with the results of previously conducted similar studies of meso-tetra-(4N-hydroxyethylpyridyl) porphyrin (H₂THOEtPyP4). Viscosity measurements show that the change in position of peripheral radicals on pyridylic ring has absolutely no effect on the laws of interaction of investigated porphyrins with DNA in case of outside binders such as CoTHOEPyP3 and ZnTHOEPyP3. In the presence of planar porphyrins, such as CuTHOEPyP3 and NiTHOEPyP3 the laws of structural changes of DNA are the same as in the case of H₂THOEtPyP3, with some differences. Comparison of different locations of peripheral radicals on pyridylic rings leads to the conclusion that H₂THOEtPyP3 and its metal complexes bind to DNA preferably more than H₂THOEtPyP4 and its metal complexes. This fact may be explained only suggesting that porphyrins with hydroxyethyl groups at 3N-position are favorably located relative to the DNA helix axis than at 4N-position.

Present research continues the development of viscometry method for studying porphyrin–DNA interactions.Water soluble cationic meso-tetra-(3$N$-alylpyridyl) porphyrin (H₂TAlPyP3) and its Cu-, Co- and Zn-containing derivatives were studied using UV-vis absorption spectroscopy and viscometry in order to clarify the effect of chemical structure (presence of double bond in structure of a side radical) of porphyrins and ability to affect the DNA structure. Their binding constant ($K_b)$ and stoichiometry ($n)$ were determined based on the absorbance spectra for each DNA–porphyrin complex. The results were compared with results of previously conducted similar studies with meso-tetra-(3$N$-hydroxyethylpyridyl) porphyrins. It was shown, that the planar porphyrins H₂TAlPyP3 and CuTAlPyP3 interact with DNA predominantly by intercalation at low relative concentrations of $r$(($r$$=$ [Porphyrin]/[DNA])) and by external binding mode at high values of $r$, whereas the change of chemical structure of peripheral radicals of porphyrins does not absolutely affect on the mechanism of interaction of outside binders CoTAlPyP3 and ZnTAlPyP3 with DNA.

A new tin(IV) corrole, 5,10,15-tris(4-methoxycarbonylphenyl) corrole tin(IV) (1-Sn) was synthesized and characterized. The DNA binding, photocleavage and anti-cancer activity were studied and compared with its free-base. The interaction of 1-Sn and its free-base 1 with calf thymus DNA had been investigated by spectroscopic methods, viscosity measurements and molecular docking analysis. The results revealed that 1-Sn and 1 could interact with calf thymus DNA via an outside groove binding mode. Furthermore, although 1 displayed no photonuclease activity, 1-Sn exhibited good photonuclease activity as indicated by agarose gel electrophoresis, and superoxide anion might be the active intermediate for the DNA scission. Finally, 1 was nontoxic but 1-Sn displayed cytotoxicity towards A549 tumor cell lines.

The influence of water soluble cationic meso-tetra-(4N-allylpyridyl) porphyrin (H₂TAlPyP4) and its metal complexes with Cu, Co and Zn on hydrodynamic and spectral behavior of DNA solutions has been studied by viscometry, CD and UV-vis spectroscopy methods. The results were compared with the results of previously conducted similar studies on meso-tetra-(3N-allylpyridyl) porphyrin (H₂TAllPyP3). It has been shown that the change in position of peripheral radicals on the pyridylic ring has absolutely no effect on the rules of interaction of investigated porphyrins with DNA in the case of outside binders CoTAllPyP4 and ZnTAllPyP4. Planar porphyrin H₂TAllPyP4 interacts with DNA predominantly by the intercalation mode at low relative concentrations of $r$ ($r=$ [Porphyrin]/[DNA]) and by external binding mode at high values of $r$. CuTAllPyP4 shows unusual behavior by interacting with DNA via a non-classical (partial) intercalation binding mode. It was shown that H${}_{\mathrm{\text{2}}}$TAllPyP3 and its metal complexes bind to DNA much more intensely than H₂TAllPyP4 and its metal complexes.

We studied the interaction of water-soluble cationic metalloporphyrins, $p$Py and TMPyP, with the DNA double helix in ionic liquid solutions using CD and absorption spectra. The dispersibility of their porphyrin complexes was improved by electrostatic interactions of the anions of the ionic liquid. In the case of Cu(II) and Zn(II) complexes, the $p$Py complexes with pyridinium cations attached to the meso-phenyl groups via methylene groups intercalated into the DNA double helix, while the compact TMPyP complexes with pyridinium cations at the meso-position could not interact with DNA. Thus, it was suggested that the solvation behavior by ionic liquids depends on the structure of the porphyrin and also affects its interaction with DNA. Neither Mn(III) complexes with axial ligands could interact with DNA, regardless of the presence of the ionic liquids, due to their steric hindrance.