Recent Publications View All

• Banerjee, R., Mukhe Insights into the role of the conserved GTPase domain residues T62 and S277 in yeast Dnm1 Int. J. Biol. Macromol. , 2023 , 253 , .

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Insights into the role of the conserved GTPase domain residues T62 and S277 in yeast Dnm1

Authors:Banerjee, R., Mukherjee, A., Adhikary. A., Sharma, S., Hussain, M.S., Ali, M. E., and Nagotu, S.

Publication Details:Int. J. Biol. Macromol.,2023, 253,

Abstract:


Mitochondrial division is a highly regulated process. The master regulator of this process is the multi-domain, conserved protein called Dnm1 in yeast. In this study, we systematically analyzed two residues, T62 and S277, reported to be putatively phosphorylated in the GTPase domain of the protein. These residues lie in the G2 and G5 motifs of the GTPase domain. Both residues are important for the function of the protein, as evident from in vivo and in vitro analysis of the non-phosphorylatable and phosphomimetic variants. Dnm1T62A/D and Dnm1S277A/D showed differences with respect to the protein localization and puncta dynamics in vivo, albeit both were non-functional as assessed by mitochondrial morphology and GTPase activity. Overall, the secondary structure of the protein variants was unaltered, but local conformational changes were observed. Interestingly, both Dnm1T62A/D and Dnm1S277A/D exhibited dominant-negative behavior when expressed in cells containing endogenous Dnm1. To our knowledge, we report for the first time a single residue (S277) change that does not alter the localization of Dnm1 but makes it non-functional in a dominant-negative manner. Intriguingly, the two residues analyzed in this study are present in the same domain but exhibit variable effects when mutated to alanine or aspartic acid.  

 

DOI Link: 10.1016/j.ijbiomac.2023.127381

• Mukhopadhyaya, A., S Probing the spin states of tetra-coordinated iron(II) porphyrins by their vibrational and pre K-edge x-ray absorption spectra Int. J. Quantum Chem. , 2023 , , .

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Probing the spin states of tetra-coordinated iron(II) porphyrins by their vibrational and pre K-edge x-ray absorption spectra



Authors:Mukhopadhyaya, A., Sharma, M., Oppeneer, P.M. and Ali, M.E.

Publication Details:Int. J. Quantum Chem.,2023, ,

Abstract:


Tetra-coordinated iron(II) porphyrins are observed in triplet (intermediate spin, IS) ground state with low-lying quintet (high spin, HS) and singlet (low spin, LS) excited states. It is well known in the literature that the d_Fe-N bond distances are dependent on the spin state such that the d_Fe-N distances are larger for HS compared to the LS/IS states. This implies the existence of strong magneto-structural correlations. Herein, the possibility to obtain the spin-state information for a series of tetra-coordinated square planar iron(II) porphyrin complexes have been explored by exploiting the magneto-structural correlations obtained from first principle calculations. The spin-state dependent nature of the chemical bonds and spin polarization on the N-atoms play a crucial role in the vibrational dynamics of the central Fe-atom. Theoretical nuclear resonance vibrational spectroscopy (NRVS) is adopted to investigate the vibrational dynamics and the Fe-atom associated spectral peaks and their spin-dependent features. We find that NRVS studies along with iron pre-K-edge x-ray absorption analysis convincingly provide the information on the spin state, which could be utilized to identify the spin states without adopting any magnetic probes.

 

DOI Link: 10.1002/qua.27174

• Nain, S., Kumar, M. The impact of spin-vibrational coupling on magnetic relaxation of a Co(ii) single-molecule magnet Phys. Chem. Chem. Phys. , 2023 , 25 , 14848-14861.

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The impact of spin-vibrational coupling on magnetic relaxation of a Co(ii) single-molecule magnet



Authors:Nain, S., Kumar, M. and Ali, M.E.

Publication Details:Phys. Chem. Chem. Phys.,2023, 25, 14848-14861

Abstract:
Single-molecule magnets (SMMs) based on transition metals have appeared as enticing targets exploiting magnetic anisotropy in 3d elements. Among transition metals, Co based SMMs are very prominent as they often exhibit a high spin-reversal barrier (Ueff), owing to their large unquenched orbital angular momentum. Employing the wave function-based multireference CASSCF/NEVPT2 calculations, herein we substantiate the zero-field splitting parameters of four mononuclear Co complexes and one of them has shown potential as an SMM. The mechanism of magnetic relaxation has been studied to understand the molecular origin of the slow relaxation of magnetization. The combination of suppressed quantum tunneling of magnetization (QTM) at the ground state and the high negative D value usually manifests SMM behavior in a zero-applied magnetic field. However, mere fulfillment of these conditions ensures little about their SMM behavior, as spin-vibrational coupling often plays spoilsport by lowering the spin relaxation channels. A detailed study accounting for all the 46 vibrational modes below the first-excited state for the prospective Co(II) complex, reveals one of the vibrational modes providing a lower spin relaxation pathway. This results in the development of an SMM with a Ueff value of 239.30 cm−1, decreased by ∼81 cm−1 from the value without spin-vibrational coupling.

DOI Link: 10.1039/D3CP01243C

• Neethu, K. M., Nag, A study of [2 + 2] cycloaddition–retroelectrocyclization in water: observation of substrate-driven transient-nanoreactor-induced new reactivity Org. Biomol. Chem. , 2023 , 21 , 2922-2929.

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A study of [2 + 2] cycloaddition–retroelectrocyclization in water: observation of substrate-driven transient-nanoreactor-induced new reactivity



Authors:Neethu, K. M., Nag, K., Dar, A. H., Bajaj, A., Gopal, S. A., Gowri, V., Nagpure, M. Sartaliya, S., Sharma, R., Solanki, Kumar A., Ali M. E., Muthukrishnan, Azhagumuthu, Jayamurugan, G.

Publication Details:Org. Biomol. Chem.,2023, 21, 2922-2929

Abstract:
Organic solvents limit [2 + 2] cycloaddition–retroelectrocyclization (CA–RE) in biological fields. We examined the formation of 1,1,4,4-tetracyanobuta-1,3-dienes (TCBDs) through CA–RE reactions and their unusual reactivity to produce N-heterocyclic compounds when the nature of the surfactant and the concentrations were varied in the aqueous phase. An environment in which transient self-assemblies (vesicles) were induced by the substrate and surfactant molecules initiated new reactivity through H2O addition on the TCBD, generating the enol form of the intermediate, which results in the formation of the 6,6-dicyano-heteropentafulvene (amidofulvene) compound, while lamellar sheets at higher concentrations favored TCBD generation. Interestingly, the amidofulvene underwent a clean transformation to 6-membered heterocycles that resemble cardiotonic drugs (milrinone, amrinone) via keto–enol tautomerism mediated by a polar aprotic solvent, opening up a new avenue for drug discovery. Unlike organic-solvent-mediated CA–RE reactions, the present nanoreactor-mediated approach enabled the selective production of TCBDs as well as new heterocycles using H2O as a green solvent. In addition to the widely explored organic electronics/materials, we believe that this study will help to overcome the long-standing limitation of CA–RE reaction applicability in biological fields.

DOI Link: 10.1039/D3OB00053B

• Bajaj, A.; Ali, Md. Anti-ohmic nanoconductors: myth, reality and promise Phys. Chem. Chem. Phys. , 2023 , 25 , 9607-9616.

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Anti-ohmic nanoconductors: myth, reality and promise



Authors:Bajaj, A.; Ali, Md. E.

Publication Details:Phys. Chem. Chem. Phys.,2023, 25, 9607-9616

Abstract:
The recent accomplishment in the design of molecular nanowires characterized by increasing conductance with length has led to the origin of an extraordinary new family of molecular junctions referred to as “anti-ohmic” wires. Herein, this highly desirable, non-classical behavior, has been examined for molecules long-enough to exhibit pronounced diradical character in their ground state within the unrestricted DFT formalism with spin symmetry breaking. We demonstrate that highly conjugated acenes signal higher resistance in an open-shell singlet (OSS) configuration as compared to their closed-shell counterparts. This anomaly has been further proven for experimentally certified cumulene wires, which reveals phenomenal modulation in the transport characteristics such that an increasing conductance is observed in the closed-shell limit, while higher cumulenes in the OSS ground state yield regular decay of conductance.

DOI Link: 10.1039/D3CP00366C

• Sharangi, P., Mukhop Effect of fullerene on the anisotropy, domain size and relaxation of a perpendicularly magnetized Pt/Co/C60/Pt system J. Mater. Chem. C , 2022 , 10 , 17236-17244.

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Effect of fullerene on the anisotropy, domain size and relaxation of a perpendicularly magnetized Pt/Co/C60/Pt system



Authors:Sharangi, P., Mukhopadhyaya, A., Mallik, S., Pandey, E., Ojha, B., Ali, M.E. and Bedanta, S.,

Publication Details:J. Mater. Chem. C,2022, 10, 17236-17244

Abstract:
Buckminsterfullerene (C₆₀) can exhibit ferromagnetism at the interface (called a spinterface) when it is placed next to a ferromagnet (FM). The formation of a spinterface occurs due to orbital hybridization and spin polarized charge transfer at the interface. The spinterface can influence the domain size and magnetization dynamics of the organic/ferromagnetic heterostructure. Here, we have performed magnetic domain imaging and studied the relaxation dynamics in Pt/Co/C₆₀/Pt systems which exhibit perpendicular anisotropy. The obtained results have been compared with a reference Pt/Co/Pt system. It is observed that the presence of C₆₀ in the Pt/Co/Pt system leads to an increase in perpendicular magnetic anisotropy and a decrease in the size of bubble domains. Furthermore, the switching time of the Pt/Co/C₆₀/Pt system is faster than its reference Pt/Co/Pt system. Spin polarized density functional theory (DFT) calculations have been performed to understand the underlying mechanism. The DFT results show the formation of a spin polarized spinterface which leads to an enhancement in anisotropy.

DOI Link: 10.1039/D2TC01347A

• Sharma, S. and Ali, How do the Mutations in PfK13 Protein Promote Anti-Malarial Drug Resistance ? J. Biomol.Struct. Dyn , 2022 , , 1-10.

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How do the Mutations in PfK13 Protein Promote Anti-Malarial Drug Resistance ?

Authors:Sharma, S. and Ali, Md. Ali.

Publication Details:J. Biomol.Struct. Dyn,2022, , 1-10

Abstract:
Plasmodium falciparum develops resistance to artemisinin upon exposure to the anti-malarial drug. Various mutations in the Plasmodium falciparum Kelch13 (PfK13) protein such as Y493H, R539T, I543T and C580Y have been associated with anti-malarial drug resistance. These mutations impede the regular ubiquitination process that eventually invokes drug resistance. However, the relationship between the mutation and the mechanism of drug resistance has not yet been fully elucidated. The comparative protein dynamics are studied by performing the classical molecular dynamics (MD) simulations and subsequent analysis of the trajectories adopting root-mean-square fluctuations, the secondary-structure predictions and the dynamical cross-correlation matrix analysis tools. Here, we observed that the mutations in the Kelch-domain do not have any structural impact on the mutated site; however, it significantly alters the overall dynamics of the protein. The loop-region of the BTB-domain especially for Y493H and C580Y mutants is found to have the enhanced dynamical fluctuations. The enhanced fluctuations in the BTB-domain could affect the protein-protein (PfK13-Cullin) binding interactions in the ubiquitination process and eventually lead to anti-malarial drug resistance.

DOI Link: 10.1080/07391102.2022.2120539

• Khurana, R.; Ali, Md Single-Molecule Magnetism in Linear Fe(I) Complexes with Aufbau and Non-Aufbau Ground States Inorg. Chem. , 2022 , 61 , 15335–15345.

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Single-Molecule Magnetism in Linear Fe(I) Complexes with Aufbau and Non-Aufbau Ground States



Authors:Khurana, R.; Ali, Md. E.

Publication Details:Inorg. Chem.,2022, 61, 15335–15345

Abstract:
With the ongoing efforts on synthesizing mononuclear single-ion magnets (SIMs) with promising applications in high-density data storage and spintronics devices, the linear or quasi-linear Fe(I) complexes emerge as the enticing candidates possessing large unquenched angular momentum. Herein, we have studied five experimentally synthesized linear Fe(I) complexes to uncover the origin of single-molecule magnetic behavior of these complexes. To begin with, we benchmarked the methodology on the experimentally and theoretically well-studied complex [Fe(C(SiMe₃)₃)₂]⁻¹(1) (SiMe₃ = trimethylsilyl), which is characterized with a large spin-reversal barrier of 226 cm^–1. Subsequently, the spin-phonon coupling coefficients are calculated for the low-frequency vibrational modes to understand the relaxation mechanism of the complex. Furthermore, the two Fe(I) complexes, that is, [Fe(cyIDep)₂]⁺¹(2) (cyIDep = 1,3-bis(2′,6′-diethylphenyl)-4,5-(CH₂)₄-imidazole-2-ylidene) and [Fe(sIDep)₂]⁺¹(3) (sIDep = 1,3-bis(2′,6′-diethylphenyl)-imidazolin-2-ylidene), are studied that are experimentally reported with no SIM behavior under ac or dc magnetic fields; however, they exhibit large opposite axial zero field splitting (−62.4 and +34.0 cm^–1, respectively) from ab initio calculations. We have unwrapped the origin of this contrasting observation between experiment and theory by probing their magnetic relaxation pathways and the pattern of d orbital splitting. Additionally, the two experimentally synthesized Fe(I) complexes, that is, [(η⁶-C₆H₆)FeAr*-3,5-Pr₂ⁱ] (4) (Ar*-3,5-Pr₂ⁱ = C₆H-2,6-(C₆H₂-2,4,6-Pr₃ⁱ)₂-3,5-Pr₂ⁱ) and [(CAAC)₂Fe]⁺¹(5) (CAAC = cyclic (alkyl) (amino)carbene), are investigated for SIM behavior, since there is no report on their magnetic anisotropy. To this end, complex 4 presents itself as the possible candidate for SIM.

DOI Link: 10.1021/acs.inorgchem.2c00981

• Ali, S., Bajaj, A.; Quantum Interference Controlled Spin-Polarized Electron Transmission in Graphene Nanoribbons J. Phys. Chem. C , 2022 , 126 , 14714–14726.

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Quantum Interference Controlled Spin-Polarized Electron Transmission in Graphene Nanoribbons



Authors:Ali, S., Bajaj, A.; Ali, Md. E.

Publication Details:J. Phys. Chem. C,2022, 126, 14714–14726

Abstract:
In graphene-based nano junctions, the edge-topology of graphene nanoribbons (GNRs) is crucial to modulate the spin-dependent transport through quantum interference (QI). Herein we have investigated the quantum transport properties of armchair GNRs (AGNRs) and zig-zag GNRs (ZGNRs) nanoribbons employing density functional theory in combination with nonequilibrium Green’s function (NEGF-DFT) techniques. The spin-polarized transmission spectra, with spin-filtering efficiency up to 50%, are observed for the ZGNRs in the low-lying ferromagnetic state. Such spin response in the transmission spectra remains silent for the non-magnetic AGNR and antiferromagnetic ZGNR in their respective ground states. Further, upon reducing the width of ZGNR, we observed that the evolved spin-dependent QI features leading to high spin-filtering efficiency.

DOI Link: 10.1021/acs.jpcc.2c04107

• Sharma, P., Sharma, Design, characterization and structure–function analysis of novel antimicrobial peptides based on the N-terminal CATH-2 fragment Sci. Rep , 2022 , 12 , 1-14.

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Design, characterization and structure–function analysis of novel antimicrobial peptides based on the N-terminal CATH-2 fragment

Authors:Sharma, P., Sharma, S., Joshi, S., Barman, P., Bhatt, A., Maan, M., Singla, N., Rishi, P., Ali, M., Preet, S. and Saini, A.

Publication Details:Sci. Rep,2022, 12, 1-14

Abstract:
The emergence of multidrug resistance coupled with shrinking antibiotic pipelines has increased the demand of antimicrobials with novel mechanisms of action. Therefore, researchers across the globe are striving to develop new antimicrobial substances to alleviate the pressure on conventional antibiotic therapies. Host-Defence Peptides (HDPs) and their derivatives are emerging as effective therapeutic agents against microbial resistance. In this study, five analogs (DP1-5) of the N-terminal (N-15) fragment of CATH-2 were designed based on the delicate balance between various physicochemical properties such as charge, aliphatic character, amphipathicity and hydrophobicity. By means of in-silico and in-vitro studies a novel peptide (DP1) with the sequence “RFGRFLRKILRFLKK” was found to be more effective and less toxic than the N-terminal CATH-2 peptide. Circular dichroism spectroscopy and differential scanning calorimetry were applied for structural insights. Antimicrobial, haemolytic, and cytotoxic activities were also assessed. The resulting peptide was characterized by low cytotoxicity, low haemolytic activity, and efficient anti-microbial activity. Structurally, it displayed strong helical properties irrespective of the solvent environment and was stable in membrane-mimicking environments. Taken together, the data suggests that DP1 can be explored as a promising therapeutic agent with possible clinical applications.

DOI Link: 10.1038/s41598-022-16303-2