key: cord-0882344-pomothl2
authors: Habib, Ahsan; Serniabad, Salma; Khan, Mohammad Shamim; Islam, Rokayea; Chakraborty, Mrittika; Nargis, Aklima; Quayum, Md Emran; Alam, Md Ashraful; rapozzi, Valentina; Tabata, Masaaki
title: Kinetics and mechanism of formation of nickel(II)porphyrin and its interaction with DNA in aqueous medium
date: 2021-08-03
journal: J Chem Sci (Bangalore)
DOI: 10.1007/s12039-021-01945-y
sha: e952d4e27ab3c99f2c1f92fa5913734ab352eaa9
doc_id: 882344
cord_uid: pomothl2

Kinetics between 5,10,15,20-tetrakis(N-methylpyridium-4-yl)porphyrin and Ni(2+) species were investigated in aqueous solution at 25 ±1 °C in I = 0.10 M (NaNO(3)). Speciation of Ni(2+) was done in I = 0.10 M (NaNO(3)) for knowing distribution of Ni(2+) species with solution pH. Experimental data were compared with speciation diagram constructed from the values of hydrolysis constants of Ni(2+) ion. Speciation data showed that hexaaquanickel(II) ions took place in hydrolysis reactions through formation of [Ni(OH(2))(6-n)(OH)(n)](2-n) species with solution pH. According to speciation of Ni(2+) and pH dependent rate constants, rate expression can be written as: d[Ni(TMPyP)(4+)]/dt = (k(1)[Ni(2+)((aq))] + k(2)[Ni(OH)(+)((aq))] + k(3)[Ni(OH)(2)(o)((aq))] + k(4)[Ni(OH)(3)(-)((aq))])[H(2)TMPyP(4+)], where k(1), k(2), k(3) and k(4) were found to be k(1) = (0.62 ± 0.22) × 10(-2); k(2) = (3.60 ± 0.40) × 10(-2); k(3) = (2.09 ± 0.52) × 10(-2), k(4) = (0.53 ± 0.04) × 10(-2) M(-1)s(-1) at 25 ±1 °C, respectively. Formation of hydrogen bonding between [Ni(H(2)O)(5)(OH)](+) and [H(2)TMPyP](4+) causes enhanced reactivity. Rate of formation of [Ni(II)TMPyP](4+) complex was to be 3.99 × 10(-2) M(-1)s(-1) in I = 0.10 M, NaNO(3) (25 ± 1 °C). UV-Vis and fluorescence data suggested that [Ni(II)TMPyP](4+) and [H(2)(TMPyP)](4+) interact with DNA via outside binding with self-stacking and intercalation, respectively. SYNOPSIS [Figure: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12039-021-01945-y.

Substantial studies by many research groups have been carried out on kinetics and mechanism of formation of metalloporphyrins because of their possible applications as therapeutic agents in medical and biological fields. [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] The structural similarity of the porphyrins with chlorophylls, green pigments of leaves, has also been attracted by researchers for their potential use in an artificial photosynthetic system. 20 In the human body system, the protoporphyrin IX ring is continuously synthesized during biosynthesis of heme, and iron(II) is subsequently coordinated to the porphyrin core. Studies of the kinetics of incorporation of metal ions into the porphyrins' core provide the mechanistic pathways of the formation of metalloporphyrins. By knowing proper reaction pathways of the formation of metalloporphyrins, it may possible to formulate porphyrin-based new drugs. Hambright and Chock (1974) proposed a general mechanism of formation of metalloporphyrins for the first time, and later that was reviewed by a number of research groups from different kinetic standpoints. [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] Among the standpoints, the presence of the hydroxo group of the central metal ion enhances the reactivity of macrocyclic porphyrins through the formation of hydrogen bonding between the oxygen atom of the hydroxo-ligand and the pyrrolic hydrogen atom of the free base porphyrin. 23, 27, 34 Nickel is an essential element for humans as well as for other animals in functioning many metabolic reactions. The known multifunctional properties of the porphyrins and metalloporphyrins have been extended the porphyrins' research in various fields. So, the study of kinetics and mechanism of the formation of Ni(II)porphyrin may open a new research arena of applications of nickel-porphyrin complexes. Nickel is a transition metal having d 8 electronic configuration, thus exhibits the least reactivity in complex formation. However, in our previous study, we found enhanced reactivity of Au 3? ion in the formation of complexes with the macrocyclic tetrakis(N-methylpyridinium-4yl)porphyrin, [H 2 TMPyP] 4? , where Au 3? ion belongs to the d 8 electronic configuration. 27 According to the speciation diagram of Au 3? ion with solution pH, the monohydroxotrichloroaurate(III), [AuCl 3 (OH)] -, was found as a predominant species under the experimental condition. 27 The negatively charged [AuCl 3 (OH)]ion can easily approach the core of the tetracationic porphyrin and the presence of the hydroxo-ligand in the Au 3? species causes enhanced reactivity in the formation of the [Au(III)TMPyP] 5? complex. This is because the hydroxo-ligand of the [AuCl 3 (OH)]species forms hydrogen bonding with the pyrrolic hydrogen atom of the porphyrin, which resulted in an enhanced rate of the reaction. Thus, it is suspected that the monohydroxonickel(II), [Ni(H 2 O) 5 (OH)] ? , species may also exhibit enhance reactivity with the free-base porphyrin, [H 2 TMPyP] 4? . In kinetic studies, the speciation of central metal ion plays a vital role to investigate the reactivity and mechanism of the reactions. Though some attempts have already been paid to study the kinetics of formation of Ni(II)porphyrins, [35] [36] [37] [38] speciation of Ni(II) ion from the geo-and hydrothermal points of view is available. 39, 40 Much attention has been paid to explore the interaction between the cationic porphyrins and nucleic acids because of the promising properties of the porphyrins in medical and biological applications. 2, 3, [5] [6] [7] [9] [10] [11] [12] [13] [14] [15] [16] [17] [41] [42] [43] [44] [45] [46] [47] [48] [49] [50] [51] The potential uses of the porphyrins in medical and biological fields are due to their anticancer, 11, 13, 17 antiviral and/or antibacterial/ anti-inflammatory 4,6,10,14-16 and antifungal 6,52 activities. Porphyrins are also being used as imaging agents in medical imaging systems. 6,53-55 Cationic porphyrins interact with DNA in various modes. Three major modes of interaction between porphyrins and DNA are intercalation, outside binding without self-stacking, and outside binding with self-stacking along the DNA surface. [41] [42] [43] [44] [45] [46] Partial intercalation has also been suggested. 45, 46 It is noted that potential applications of porphyrins in medical and biological systems depend mainly on the modes of interaction of the porphyrin-DNA adducts.

Very recently Liu and Li (2020) studied the severe health effect of the novel coronavirus (COVID-19) worldwide by applying theoretical models. 56, 57 They used conserved domain analysis, homology modeling and molecular docking models to compare the biological roles of specific proteins of the COVID-19, and found the novel coronavirus attacks the 1-beta chain of the haemoglobin and captures the protoporphyrin IX to inhibit human heme metabolism. The theoretical results suggest that the coronavirus has a strong affinity for porphyrins. The noble but clinically relevant finding encouraged us to investigate possible applications of the porphyrins as anti-COVID-19 agents.

In this paper, speciation of Ni 2? in an aqueous medium with different solution pH in I = 0.10 M (NaNO 3 ) and 0.10 M NaCl at 25 ±1°C has been characterized. By applying the distribution of the Ni 2? solution was used to standardize the porphyrin solution by using spectrophotometric titration (molar ratio method). 27, 46, 47 Nickel solution was prepared by dissolving the requisite amount of NiCl 2 .6H 2 O (Merck, Germany) in an aqueous solution and the concentration was measured by using an atomic absorption spectrophotometer (Perkin Elmer, AAanalyst 200). Sodium nitrate, sodium hydroxide and hydrochloric acid were purchased from Merck, Germany. All the chemicals/ reagents were used without further purification. Tetracation nickel(II) porphyrin, [Ni(II)TMPyP] 4? , was prepared and absorption spectra were recorded in water at pH 9.50 containing 0.10 M NaNO 3 . Absorption maximum (k max ) and molar extinction coefficient (e) of the prepared [Ni(II)TMPyP] 4? complex were 436 nm and 114 9 10 3 M -1 cm -1 , respectively ( Figure 1 ). 58 A stock solution of salmon fish sperm DNA, purchased from Sigma-Aldrich, was prepared by dissolving in distilled water and the concentration in base pairs was determined by knowing the absorbance at k max = 260 nm and using the molar extinction coefficient, e 260 =1.32 9 104 M -1 cm -1 . 45, 46 Stock solution of the DNA was kept in a refrigerator at -4°C. The frozen DNA solution was incubated in a water bath at 37°C for an hour and diluted as required before the experiment. Acetate/sodium acetate and 2-[4-(2-hydroxyethyl)-1-piperazinyl] ethanesulfonic acid (HEPES, Sigma-Aldrich) buffer solution was prepared in 100 mL distilled water as stock solutions and used with required dilution throughout the experiments. pH of the HEPES solution (0.10 M) was adjusted to 7.40 upon addition of either NaOH or HCl. In this work, distilled water was used to perform all the experiments.

Solutions of 5.00 9 10 -3 M NiCl 2 with changing solution pH from 2.97 to 11.40, were prepared in 50 mL volumetric flasks separately. The requisite volume of sodium nitrate was added to each solution in order to maintain ionic strength (I = 0.10 M). Solution pH was adjusted by the addition of either HCl or NaOH in acetate buffer ([Acetate] = 0.02 M). The UV-Vis spectra of the Ni 2? species were recorded by using a double beam UV-Vis spectrophotometer (SHIMADZU, Model UV-1800) within a range from 350 to 500 nm. A number of Ni 2? solutions (5.00 9 10 -3 M) with different concentration of acetate ion ranging from 0 to 1.00 910 -2 M was prepared under the same experimental conditions to investigate the interaction between Ni 2? and acetate ions and found no formation of Ni(II)acetate complex. A pH meter (HANNA HI 2211) was used to measure the solution pH. 

Pseudo-first order condition was kept constant throughout the experiment in order to explore the kinetics of the reactions between tetracationic freebase porphyrin and Ni 2? species in I = 0.10 M (NaNO 3 ) at 25 ±1°C where the pH of the solutions were varied from 2.97 to 11.05. The concentration of Ni 2? was varied from 0.50 9 10 -3 to 5.00 9 10 -3 M while that for the porphyrin, [H 2 TMPyP] 4? , was kept constant at 1.24 9 10 -5 M. The metalloporphyrin was prepared by mixing the porphyrin solution with the Ni 2? solution in a 1-cm cell compartment and preequilibrated at 25 ±1°C. The change in the absorbance was monitored as a function of time at 422 nm (k max of [H 2 TMPyP] 4? ) by using a UV-Vis spectrophotometer (SHIMADZU, Model UV-1800). Formation of the [Ni(II)TMPyP] 4? complex was monitored by observing isosbestic points at 431, 490 and 546 nm in the visible region as the porphyrin reacted with the Ni 2? species. Appearing the isosbestic points is confirming the free-base porphyrin and Ni(II)porphyrin complex are only the absorbing species. Figure 1 shows such a spectral pattern of the formation of the [Ni(II)TMPyP] 4? complex with time.

To obtain the observed rate constants (k obs ), values of ln(A t -A a ) were plotted with time and found linearity over two half-lives. Rate constants for the reactions between the free-base porphyrin and Ni 2? species were determined by varying solution pH, nickel concentrations and ionic strengths. The duplicate runs under the same conditions agreed within a 5% error. A pH meter (HANNA HI 2211) was used to measure the pH of the solution.

The UV-Vis spectra of the free base porphyrin and [Ni(II)TMPyP] 4? complex upon addition of DNA were recorded by using a double-beam UV-Vis spectrophotometer (UV-1800, Shimadzu, Japan). A fluorescence spectrophotometer (F-7000, Hitachi, Japan) was used to record the luminescence spectra for the free base porphyrin and the Ni(II)porphyrin in the presence of DNA. The fluorescence emission wavelength was scanned from 550 to 800 nm by setting the excitation wavelength at 446 4 ? , the absorbance and luminescence spectra of the porphyrin solutions were not affected by the species adsorbed on the surface of the cell wall. These were confirmed by recording a UV-vis spectrum of ethanol-water after discarding the analyte solution and found no peaks from the ethanol-water. All the experiments were carried out under room light. HEPES solution of 0.02 M (pH 7.40) was used throughout the experiment. A pH meter (HANNA HI 2211) was used to measure the solution pH.

Speciation of Ni 2? ion in aqueous solution in the presence of 0.10 M of NaNO 3 (I) at 25 ±1°C was carried out to investigate the kinetics of the reaction between the free-base porphyrin, [H 2 TMPyP] 4? , and the Ni 2? species. In order to investigate the kinetics of the metalation reaction, it is highly expected to know the speciation of the relevant metal ion. This is because the speciation diagram provides species distribution that is required to establish the reaction mechanism for the relevant reaction. Figure 2 shows the speciation diagram generated from the hydrolysis constants of Ni 2? species with the solution pH. 59 As (aq) , species predominantly exists from the acidic to even alkaline pH (*9.50) and is converting to hydroxo species, [Ni(H 2 O) 6-n (OH) n ] 2-n , through successive replacement of the H 2 O molecule by the OHgroups with increasing the solution pH. The aqua-monohydroxo Ni 2? , [Ni(H 2 O) 5 (OH)] ? , species is distributed from pH *7.90 to 11.00 with the maximum distribution that observed at pH 9.50 ( Figure 2 ). Like Ni 2?

(aq) ions, the monohydroxo Ni 2? ions, [Ni(H 2-O) 5 (OH)] ? , are also aquatic species, thus they take part in metalation reaction with the water-soluble free-base porphyrin, [H 2 TMPyP] 4? , significantly in the aqueous medium.

On the other hand, a small fraction of the dihydroxo Ni 2? , [Ni(H 2 O) 4 (OH) 2 ] 0 , species reacts with the free-base porphyrin, [H 2 TMPyP] 4? , because of its very poor existence in the aqueous system under the present experimental conditions. The solubility product for the dihydroxo Ni 2? species is only K b S10 = -15.7, thus it starts to precipitate at pH *8.15 for 10 -3 M of Ni 2? solution. 59 This causes the presence of a small fraction of the [Ni(H 2 O) 4 (OH) 2 ] 0 species in this study ( Figure 2 ). According to the speciation diagram, the [Ni(H 2 O) 4 (OH) 2 ] 0 species is distributed from pH *8.25 to the higher pH ( C 12.00) where its maximum distribution is observed at pH *10.30 ( Figure 2 3 ]species is distributed from pH 9.4 to the higher pH [ 12.00 while its distribution is so small *1-2% at the experimental solution pH, 9.50 ( Figure 2) .

The UV-Vis spectral data also confirm the stepwise formation of the hydroxo Ni 2? , [Ni(H 2 O) 6-n (OH) n ] 2-n , species as a function of the solution pH (Figure S1, Supplementary Information). As mentioned above, the 6 ] 2? species shows the ligand to metal charge transfer (LMCT) transition and the absorption maximum is centered at k max = 391 nm in the UV region ( Figure S1 , Supplementary Information). The LMCT transitions have been assigned due to the charge transfer from bonding or nonbonding p-orbital of ligand to high energy antibonding dp*-orbital of the metal ion. 60 The UV-Vis absorption spectra for Ni 2? (1.0910 -3 M) in 0.10 M NaNO 3 solutions with different solution pH are shown in Figure S1 , Supplementary Information. As seen from Figure S1 , Supplementary Information, the intensity of the peak centered at k max 391 nm that gradually decreases as a function of solution pH and reaches at a flat with the higher pH value, *10. 30 4 (OH) 2 ] 0 , species and then phases out from the aqueous solution as Ni(OH) 2 0 (K b S10 = -15.7), thereby resulting in presence of an insignificant amount of the UV-active species in the aqueous system ( Figure S1 , Supplementary Information). 59 

where k obs is the observed first-order rate constant and k f is the second order formation rate constant. From the reactions between the [H 2 TMPyP] 4? and Ni 2? species at different solution pH, the observed rate constants (k obs ) were measured to explore the reactivity of the various [Ni(H 2 O) 6-n (OH) n ] 2-n species. The values of the observed rate constants for the reactions of the free base porphyrins with the Ni 2? species as a function of solution pH are shown in Figure 3 . As seen from Figure 3 , the observed rate constant increases as a function of the solution pH and goes to its maximum value at pH 9.50 and then slows down as pH is being increased. The rising trend for the rate constants almost remains constant until pH 6.60 and then increases sharply with pH. These results suggest that the reacting species of the Ni 2? ion is mostly hexaaqua Ni 2? ion, [Ni(H 2 O) 6 ] 2? written as Ni 2?

(aq) , within the pH range from 2.97 to *8.00 which is one of the less reactive among the [Ni(H 2 O) 6-n (OH) n ] 2-n [n = 1, ….,6] species ( Figure 2) . Thus, at low pH (3.00-6.60) and 0. 10 4 2-] species as a function of solution pH that stated in equations 1-4. In our previous study, it has also been reported that Zn 2? ion exists predominantly as a hexaaqua, [Zn(H 2 O) 6 ] 2? , species at low pH (*2-5) in 0.10 M NaNO 3 , and changes to hydroxo species stepwise and finally converts to tetrahydroxo [Zn(OH) 4 -] species at higher solution pH. 34 As mentioned above, Ni 2? ion predominantly exists as hexaaquanickel(II), [Ni(H 2 O) 6 ] 2? , species at solution pH 3.0-8.0 and showed less reactivity in incorporation into the free base porphyrin, H 2 TMPyP 4? . As the distribution of aqua-monohydroxo, [Ni(H 2 O) 5 (OH)] ? , species increases, the reactivity of the Ni 2? ion also increases. As shown in Figure 3 , the maximum observed rate constant is found at pH 9.50. This result is confirming the maximum distribution of the [Ni(H 2 O) 5 

Ni(OH) þ ðaqÞ þ H 2 P 4þ

Ni(OH) 2ðaqÞ þ H 2 P 4þ 4 ? is very poor and its negligible presence at pH 9.50, thus, eqs. (10) can be ignored. Therefore, eqs. (6) to (9) are taken into account in order to calculate the observed rate constants, k obs . Therefore; k obs ¼ k 1 Ni 2þ

As described above, the speciation diagram exhibited the distribution of the Ni 2? species, [Ni(H 2 O) 6n (OH) n ] 2-n , with solution pH, accordingly, their kinetics were also different. According to equ (11) , the rate constants such as k 1 , k 2 , k 3 and k 4 belong to hexaaquanickel(II), dihydroxonickel(II), trihydroxonickelate(II) and tetrahydroxonickelate(II) species, respectively. Thus, the individual rate constant was calculated by taking as a mean of the observed rate constants. The calculated observed rate constants are as follows: k 1 = (0.62 ± 0.22) 9 10 -2 ; k 2 = (3.60 ± 0.40) 9 10 -2 ; k 3 = (2.09 ± 0.52) 9 10 -2 , k 4 = (0.53 ± 0.04) 9 10 -2 M -1 s -1 at 25 ±1°C in I = 0. 10 . 34 The monohydroxotrichloroaurate(III) species, [AuCl 3 (OH)] -, also showed enhanced reactivity towards the [H 2-TMPyP] 4 27 Schneider (1975) reported that monohydroxocopper(II), [Cu(OH)] ? , species exhibited much more reactivity towards the same free base porphyrin, [H 2 TMPyP] 4? , compared to that of aquacopper(II), Cu 2?

(aq) , species, i.e., k Cu(OH)

? . 63 The oxygen atom of the [Cu(OH)] ? species forms H-bonding with the pyrrolic hydrogen atom of the porphyrin core. This is the reason for its substantial reactivity with the free base porphyrin. It is, therefore, concluded that the presence of the OHgroup of the aqua-monohydroxo, [Ni(H 2 O) 5 27 Paquette and Zador (1978) also reported that the reactivity of Zn 2? ion towards hematoporphyrin IX decreases with an increasing number of the OHgroup coordinated to the Zn 2? ion and the reactivity order follows the sequence: 60 Cabbiness and Margerum (1969) . This is because the aqua-dihydroxonickel(II) species take part in hydrolysis reaction at solution pH 8.20 and then phases out from the aqueous system through precipitation reaction at higher pH, e.g., 9.50. The precipitation reaction causes lesser distribution of the dihydroxonickel(II) species compared to the aquamonohydroxonickel(II) species at solution pH 9.50 ( Figure 2 ). The anionic trihydroxonickelate(II), [Ni(H 2 O) 3 (OH) 3 ] -, species seems to be exhibited better reactivity towards the cationic porphyrin ([H 2-TMPyP] 4? ), however, the presence of the higher number of the hydroxo groups slows down its kinetics. 27, 32, 34, 60 These results suggest that though the first OHligand is responsible for the formation of hydrogen bonding with the pyrrolic hydrogen atom, however, displacement of the remaining OHseems slow.

It has been reported that the OHgroup is strongly coordinated to the metal ion having d 8 electronic configuration like Pt 2? ion. 64 The electronic configuration of Ni 2? is also d 8 , so their chemical properties are supposed to be similar; hence the OHgroups are also strongly coordinated with the Ni 2? ion. Bailey and Hambright (2003) reported that Cu 2? ion exhibited the highest reactivity among the other first transition metal ions, such as Zn 2? , Co 2? and Ni 2? towards the free base H 2 -BrP(4) 4? and tricationic H-BrP(4) 3? porphyrins at 25°C in I = 0.10 M (NaNO 3 ) and the reactivity order was found to be Cu 2?

[ Zn 2? [ Co 2? [ Ni 2? . 65 It is expected that the reactivity of Ni 2? among the divalent metal ions towards the porphyrins would be less because of its d 8 electronic configuration. However, the presence of hydroxo-ligands with the Ni 2? species enhances its reactivity in incorporation with the free-base porphyrin, [H 2 TMPyP] 4? . Similar results have also been observed for Au 3? ion (d 8 electronic configuration) towards the [H 2 TMPyP] 4? . 27 

Kinetics of the incorporation of Ni 2? ion into the [H 2 TMPyP] 4? with a variation of the concentration of Ni 2? (I = 0.10 M, NaNO 3 ; pH 9.50) at 25 ±1°C has also been studied in order to ascertain the formation rate constant for the metalation reaction. The observed rate constants (k obs ) with a concentration of Ni 2? were 

The rate constants of a reaction for opposite charged reacting species decrease as the ionic strength increases while that increase for the same charged species. 66 Figure 5 shows the dependence of the ionic strength on the rate constants for the reaction between the free-base porphyrin, [H 2 TMPyP] 4? , and Ni 2? species in I = 0 -10.0 9 10 -2 M (NaNO 3 ) at pH 9.50 where the experimental conditions were kept constant. The observed rate constants (k obs ) were obtained by plotting the ln(A t -A a ) vs time at different ionic strengths ( Figure 5 ). As seen from Figure 5 , the observed rate constants (k obs ) exponentially decrease with the ionic strengths. These results suggest that the reacting compounds exist as oppositely charged species in solution, however, the speciation diagram is indicating the existence of the monopositive monohydroxo Ni 2? , [Ni(H 2 O) 5 (OH)] ? , species at solution pH 9.50. In our previous study, we also found the retardation of the kinetics between the dihydroxo 4 ? also decrease exponentially with ionic strength and the calculated net charge of the free base porphyrin was found to be ?3.4 by using the Fuoss equation. 27 However, in this study, we found a less decreasing tendency of the rate constants as the ionic strength increases. This may be due to the existence of monopositive monohydroxo ion took part in the reactions with the free-base porphyrin, [H 2 TMPyP] 4? , at pH 9.50. 6,27,34 Figure 6 shows the Brønsted-Bjerrum plot for nickel incorporation into the tetracationic porphyrin, [H 2-TMPyP] 4? , where Debye-Hückel Limiting (DHL) ionic strength function was applied. As seen from Figure 6 , regression coefficient (R 2 ), error bars and slope for the plot are 0.974, 1% and -3.59, respectively. It is expected that the intercept for the plot of logk obs vs HI should be zero, however, that is observed as -0.273. This is because of the presence of inherent ions that cause intrinsic ionic strength. Nwaeme and Hambright (1984) studied the effects of ionic strength on the rate of the reactions for both the positive and negative porphyrins with divalent metal ions. 67 They reported that the rates of the reactions for positive porphyrins with positive divalent metal ions increase as increasing the ionic strength and that decrease for oppositely charged reacting species with the ionic strength. Williams et al. (1979) also reported the anionic effect on the reaction rate for tetracationic porphyrins in detergent solution. 68 According to the speciation diagram (Figure 2 Figure S2b, Supplementary Information) . The heavy atom effect by the nickel causes weak intensity for the [Ni(II)TMPyP] 4? complex. In our previous study, we also found weak intensities from the Ru 2? -, Pd 2? -, Pt 2? -and [Au(III)TMPyP] 5? porphyrins in an aqueous solution because of the heavy atom effect. 45, 46 The fluorescence intensity for the [Ni(II)TMPyP] 4? complex is significantly decreased upon addition of a low concentration of DNA, and then increased with further addition of DNA ( Figure S2a , Supplementary  Information) . The porphyrin molecules aggregate on the negatively charged phosphate network of the DNA molecules through self-stacking in the presence of a low concentration of DNA, however, de-aggregation occurs upon the addition of additional DNA. This causes the increasing the fluorescence intensity of the metalloporphyrin. 45, 46 On the other hand, the intensity of the fluorescence centered at 660 nm did not change but the intensity of the hump appeared at *628 nm is increased with a low concentration of DNA into the [H 2 TMPyP] 4? solution. The intensity of the hump increases with the addition of DNA and the fluorescence spectrum is finally centered at 630 nm ( Figure S2b , Supplementary  Information) . These results suggested that the cationic free base porphyrin initially interacts with DNA via a negatively charged phosphate network in the presence of a low concentration of DNA, and then de-stacking occurs upon further addition of DNA. 45, 46 From the UV-vis and fluorescence spectral results, it is confirmed that both the metalloporphyrin, [Ni(II)TMPyP] 4? , and the free base porphyrin interact with DNA but their modes of interaction are different. As seen from Figure 6a , the hypochromicity and Bathochromic shift (Dk) for the [Ni(II)TMPyP] 4? are only * 13% (at k max 436 nm) and *1 nm upon addition of high concentration of DNA, respectively. These results suggested that [Ni(II)TMPyP] 4? interacts with DNA via outside binding with self-stacking. [41] [42] [43] [44] [45] [46] However, the significant hypochromicity (* 31% at 422 nm) and a wide Bathochromic shift (Dk = 17 nm) for the free base porphyrin upon addition of the same amount of DNA confirm its interaction with DNA through intercalation. [41] [42] [43] [44] [45] [46] The presence of metal ion in the porphyrin core is responsible for carrying water molecules as axial ligands that make the bulkiness of the metalloporphyrin molecules. The large size of the metalloporphyrin molecules interact with DNA via outside binding rather than intercalation, however, the free base porphyrin interacts with DNA via intercalation because of its smaller size that facilitates easy excess into the DNA grooves. Metalloporphyrins that are outside binders have catalytic effects to cleave DNA, 45, 46, 71, 72 thus it is expected that the [Ni(II)TMPyP] 4? complex can be used as a chemotherapeutic agent in the medical as well as in the biological fields.

In this work, kinetics and mechanism of formation of [Ni(II)TMPyP] 4? have been studied at 25 ±1°C in I = 0.10 M (NaNO 3 ) within a pH range from 2.97 to 11.40 in an aqueous medium. Speciation of Ni 2? ions in an aqueous medium has also been done in 0.10 M NaNO 3 in order to provide the distribution of the Ni 2? species as a function of solution pH for the kinetic study. The experimental data have been compared with the speciation diagram generated from the values of hydrolysis constants of Ni 2? ion. The speciation data exhibited the stepwise formation of [Ni(H 2 O) 6 Total concentration of porphyrin is 1.14 9 10 -5 M. Cell path length is 10 mm.

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Kinetics and mechanisms of metalloporphyrin reactions Coord

-sulfonatophenyl) porphine and its differential rates as applied to the kinetic determination of copper(II) and zinc(II) in serum Microchim

Kinetics and mechanism of cadmium(II) ion assisted incorporation of manganese(II) into 5,10,15,20tetrakis(4-sulphonatophenyl)-porphyrinate(4-)

Kinetics and mechanism of gold(III) incorporation into tetrakis(1-methylpyridium-4-yl)porphyrin in aqueous solution

Porphyrindiketopyrrolopyrrole conjugates and related structures: Synthesis, properties and applications

Exchange reactions of transition metal ions and labile cadmium porphyrins

Kinetics and mechanism for the formation and dissociation reactions of 21-(4-nitrobenzyl

Macrocyclic effect on the stability of copper(II) tetramine complexes

The Chemistry and Biochemistry of N-Substituted Porphyrins

Kinetics and mechanism of incorporation of zinc(II) into tetrakis(1-methylpyridium-4-yl)porphyrin in aqueous solution Arab

Kinetics of metal-ion complexation with N-methyltetraphenylporphyrin. Evidence concerning a general mechanism of porphyrin metalation

Activation parameters and a mechanism for metal-porphyrin formation reactions

The Kinetics of the incorporation of metals into tetraphenylporphyrin with metal salts in high-temperature water Indust

Insertion of Ni(I) into porphyrins at room temperature: preparation of Ni(II)-porphyrins, and Ni(II)chlorins and observation of hydroporphyrin intermediates

Sorption Speciation of Nickel(II) onto Ca-Montmorillonite: Batch, EXAFS Techniques and Modeling Dalton Trans

Speciation of nickel(II) chloride complexes in hydrothermal fluids

Intercalative and nonintercalative binding of large cationic porphyrin ligands to calf thymus DNA Nucl. Acids Res

Intercalation of tetracationic metalloporphyrins and related compounds into DNA

Porphyrin-nucleic acid interactions: a review

N-methylpyridinium-4-yl)porphyrin fully intercalates at 5'-CG-3' steps of duplex DNA in solution Biochem

Fluorescence and phosphorescence spectra of Au(III), Pt(II) and Pd(II) porphyrins with DNA at room temperature Inorg

Interactions of DNA with H2TMPyP4? and Ru(II)TMPyP4?: Probable Lead Compounds for African Sleeping Sickness Bangla Pharma

DNA photocleavage, singlet oxygen photogeneration and two photon absorption properties of ruthenium-phenanthroline porphyrins

Conjugating a groovebinding motif to an Ir(iii) complex for the enhancement of G-quadruplex probe behavior

Targeted live-cell nuclear delivery of the DNA 'light-switching' Ru(II) complex via ion-pairing with chlorophenolate counter-anions: the critical role of binding stability and lipophilicity of the ion-pairing complexes

Structural intermediates of a DNA-ligase complex illuminate the role of the catalytic metal ion and mechanism of phosphodiester bond formation

Beyond solvent exclusion: i-Motif detecting capability and an alternative DNA light-switching mechanism in a ruthenium(II) polypyridyl complex

Preparation, nano purification, quality control and labeling optimization of

Development of a radiothallium(III) labeld porphyrin complex as a potential imaging agent Radiochim

COVID-19 Disease: ORF8 and Surface Glycoprotein Inhibit Heme Metabolism by Binding to Porphyrin ChemRxiv

COVID-19: hemoglobin, iron, and hypoxia beyond inflammation. A narrative review Clin

Chemistry of Water Soluble

The Hydrolysis of Cations

Kinetics of interaction of Zn(II) with hematoporphyrin IX in basic aqueous solution

Peripheral charge effects on the kinetics of Zn(II)-porphyrin system

The effects of peripheral substituents on the kinetics of zinc ion incorporation and acid catalyzed removal from water soluble sulfonated porphyrins

Kinetics and mechanism of metalloporphyrin formation

Hard and soft acids and bases

Kinetics of the reactions of divalent copper, zinc, cobalt, and nickel with a deformed water soluble centrally monoprotic porphyrin Inorg

Effect of ionic strength on the kinetics of trypsin and alpha chymotrypsin

Magnitudes of ionic strength effects in porphyrin metalation and acid solvolysis reactions

Synthesis, characterization and copper incorporation into 5-(4-pyridyl)-10,15,20-triphenylporphyrin Inorg

The Porphyrins D Dolphin

Study of the aqueous equilibrium system involving meso-tetrapyridylporphine, alkali metal ions, and hydrogen ions

Metalloporphyrin mediated DNA cleavage by a low concentration of HaeIII restriction enzyme

DNA Cleavage and Trypanosomes Death by a Combination of Alamar Blue and Au(III)

The authors acknowledge the Ministry of Science and Technology, the People's Republic of Bangladesh for financial support to carry out this work under the project ''Photoelectrochemical splitting of water into hydrogen using solar light''.

Competing interests The authors declare no competing financial/commercial interest.

Absorption spectra of Ni(II) in 0. 10