Unraveling the Electronic Structure, Spin States, Optical and Vibrational Spectra of Malaria Pigment

Abstract

A detailed knowledge of the electronic structure and magnetic and optical properties of hemozoin, the malaria pigment, is essential for the design of effective antimalarial drugs and malarial diagnosis. By employing state-of-the-art electronic structure calculations, we have performed an in-depth investigation of the malaria pigment. Specifically, molecular bond lengths and spin states of the two Fe(III) heme centers and their exchange interaction, the UV/Vis absorption spectrum, and the IR vibrational spectra were calculated and compared with available experimental data. Our density functional theory (DFT)-based calculations predict a singlet ground spin state that stems from an S=5/2 spin state on each of the Fe heme centers with a very weak antiferromagnetic exchange interaction between them. Our theoretical UV/Vis and IR spectra provide explanations for various spectroscopic studies of hemozoin and β-hematin (a synthetic analogue of hemozoin). A good comparison of calculated and measured properties demonstrates the convincing unveiling of the electronic structure of the malaria pigment. Based on the predicted vibrational spectra, we propose a unique spectral band from the nuclear resonance vibrational spectroscopy (NRVS) results that could be used as a key fingerprint for malarial detection.

An improved model for malaria pigment and β‐hematin: Fe(OEP)picrate

“…The extraordinary band enhancement observed when exciting with near‐infrared excitation wavelengths in β ‐H when compared with hemin was explained in terms of an aggregated enhanced Raman scattering hypothesis based on the intermolecular excitonic interactions between porphyrinic units that occurs upon excitation into this broad low‐lying electronic transition centered at 867 nm . Ali and Openeer recently performed high‐level time‐dependent density functional theory (DFT) calculations to simulate the UV–Vis absorption spectrum of Hmz. The theoretical spectra matched very well with the available experimental spectra.…”

Nonreductive homolytic scission of endoperoxide bond for activation of artemisinin: A parallel mechanism to Heterolytic cleavage

“…[6] To avoid this toxicity, the parasite converts it into hematin which undergoes dimerization to form beta-hematin and then undergoes the biocrystallization process to form hemozoin, which is known as malaria pigment. [7][8][9] The traditional quinoline-based antimalarial drugs such as chloroquine and quinine function by inhibiting the beta-hematin formation due to reversible binding of the drug at the axial position of the free heme. [10][11][12][13] The toxicity of free heme is responsible for the death of the parasite.…”

“…[ 6 ] To avoid this toxicity, the parasite converts it into hematin which undergoes dimerization to form beta‐hematin and then undergoes the biocrystallization process to form hemozoin, which is known as malaria pigment. [ 7–9 ]…”

Non-reductive Homolytic Scission of Endoperoxide Bond for Activation of Artemisinin: The Bi-radical Perspectives

“…6 To avoid this toxicity, the parasite converts it into hematin which undergoes dimerization to form beta-hematin and then undergoes the bio-crystallization process to form hemozoin, which is known as malaria pigment. [7][8][9] The traditional quinoline based antimalarial drugs such as chloroquine and quinine function by inhibiting the beta-hematin formation due to reversible binding of the drug at the axial position of the free-heme. [10][11][12][13][14] The toxicity of free heme is responsible for the death of the parasite.…”