Theoretical study of the interaction between a high‐valent manganese porphyrin oxyl‐(hydroxo)‐Mn(IV)‐TMPyP and double‐stranded DNA

Abstract

Cationic porphyrin derivatives such as meso-tetrakis(4-N-methylpyridinium)porphyrin, TMPyP, have been shown to interact with double-stranded DNA. The manganese derivative, Mn(III)-TMPyP, activated by an oxygen donor like potassium monopersulfate, provides an efficient DNA-cleaving system. Previous experimental work1 has shown that DNA cleavage by the Mn(III)-TMPyP/KHSO(5) system was due to an oxidative attack, within the minor groove of B-DNA, at the C5' or C1' carbons of deoxyribose units. The aim of this study was to use molecular modeling to elucidate the specificity of the interactions between the transient active species oxyl-Mn(IV)-TMPyP and the DNA target. Geometric parameters, charges, and force field constants consistent with the AMBER 98 force field were calculated by DFT methods. Molecular modeling (mechanics and dynamic simulations) were performed for oxyl-(hydroxo)-Mn(IV)-TMPyP bound in the minor groove of the dodecamer d(5'-TCGTCAAACCGC)-d(5'-GCGGTTTGACGA). Geometry, interactions, and binding energy of the metalloporphyrin located at the A.T triplet region of the dodecamer were analyzed. These studies show no significant structural change of the DNA structure upon ligand binding. Mobility of the metalloporphyrin in the minor groove was restrained by the formation of a hydrogen bond between the hydroxo ligand trans to the metal-oxyl and a DNA phosphate, restricting the access of the oxyl group to the (pro-S) H atom at C5'.

Interaction of Cationic Nickel and Manganese Porphyrins with the Minor Groove of DNA

“…46,47,51 The preferred binding and cleavage site of Mn-TMPyP/KHSO 5 consists of three consecutive AT base pairs, referred to as an (AT) 3 box. [44][45][46][47]52 The binding constant of Mn-TMPyP for this particular site is very high: 10 6 -10 7 M -1 . 7,23, 43 In the absence of KHSO 5 , Mn-TMPyP binds to DNA but is unable to perform oxidative cleavage.…”

Porphyrins in complex with DNA: Modes of interaction and oxidation reactions

“…As will be detailed later, the signature of minor groove location of Mn III -TMPyP4 is the 3'-shifted DNA M a n u s c r i p t cleavage of complementary DNA strands [60]. Molecular modelling studies of the interaction of its corresponding oxo-manganese species confirm that minor groove interaction is possible for di-axially liganded metalloporphyrins [61]. Ni II -TMPyP4 was found in the minor groove in a crystal structure, this second mode of binding was a consequence of crystal packing [57].…”

“…A) Modeling of the interaction of high-valent manganese porphyrin oxyl-(hydroxo)-Mn IV -TMPyP4 and double-stranded DNA dodecamer 5'-d(TCGTCAAACCGC)/5'-d(GCGGTTTGACGA)[61] showing the C5'-carbon that is…”

The Interaction of Water‐Soluble Manganese Porphyrins with DNA Films and Their Electrocatalytic Properties with Hydrazine

“…The interactions of meso-tetrakis-(N-methyl-4-pyridyl)porphyrin and DNA with porphyrins have been studied using spectroscopic methods [13 -18], a kinetic method [19], and have been the subject of a theoretical study [20]. These have focused on the interactions of porphyrins [21 -26].…”