Recent Publications View All

• 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

• Bhatt, A., Mukhopadh α-Helix in Cystathionine -Synthase Enzyme Acts as Electron Reservoir J. Phys. Chem. B , 2022 , 126 , 4754-4760.

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α-Helix in Cystathionine -Synthase Enzyme Acts as Electron Reservoir



Authors:Bhatt, A., Mukhopadhyaya, A.; Ali, Md. E.

Publication Details:J. Phys. Chem. B,2022, 126, 4754-4760

Abstract:
The modulation of electron density at the Pyridoxal 5′-phosphate (PLP) catalytic center, because of charge transfer across the α-helix/PLP interface, is the determining factor for the enzymatic activities in the human Cystathionine β-Synthase (hCBS) enzyme. Applying density functional theory calculations, in conjunction with the real space density analysis, we investigated the charge density delocalization across the entire heme−α-helix–PLP electron communication channels. The electron delocalization due to hydrogen bonds at the heme/α-helix and α-helix/PLP interfaces are found to be extended over a very long range, as a result of redistribution of electron densities of the cofactors. Moreover, the internal hydrogen bonds of α-helix that are crucial for its secondary structure also participate in the electron redistribution through the structured hydrogen-bond network. α-Helix is found to accumulate the electron density at the ground state from both of the cofactors and behaves as an electron reservoir for catalytic reaction at the electrophilic center of PLP.

DOI Link: 10.1021/acs.jpcb.2c01657

• Sharma, S. and Ali, Nonreductive homolytic scission of endoperoxide bond for activation of artemisinin: A parallel mechanism to Heterolytic cleavage J. Phys. Org. Chem , 2022 , , (accepted).

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



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

Publication Details:J. Phys. Org. Chem,2022, , (accepted)

Abstract:
Artemisinin is the most successful antimalarial drug against malaria caused by Plasmodium falciparum. Despite its tremendous success and popularity in malaria therapeutics, the molecular mechanism of artemisinin's activity is still elusive. The activation of artemisinin, i.e., cleavage of the endoperoxide bond at the infected cell that generates radical intermediates and the subsequent chemical rearrangements, plays a key role in the antimalarial activities. In this work, adopting state-of-the-art computational techniques based on the spin-constrained density functional theory (CDFT) along with ab initio thermodynamics, we have investigated the activation of artemisinin by two different pathways, homolytic and heterolytic cleavage. The homolytic scission of the endoperoxide bond is further followed by subsequent chemical reactions that propagate via biradical intermediates. Here we report that the free energy of activation of artemisinin associated with the homolytic cleavage is less (21.77 kcal/mol) than the heterolytic cleavage (23.64 kcal/mol). The nonreductive homolytic cleavage of the endoperoxide bond is thermodynamically slightly favorable. Thus, the latter could occur in parallel with the heterolytic activation of the artemisinin.

DOI Link: 10.1002/poc.4392

• Gupta, D., Bhatt, A. Photo-Chemically Sequestered Off-Pathway Dormant States of Peptide Amphiphiles for Predictive On-demand Piezo-responsive Nanostructures Chem. Mater , 2022 , 34 , 4456 - 4470.

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Photo-Chemically Sequestered Off-Pathway Dormant States of Peptide Amphiphiles for Predictive On-demand Piezo-responsive Nanostructures



Authors:Gupta, D., Bhatt, A., Gupta, V., Miglani, C., Joseph, J. P., Ralhan, J., Mandal, D., Ali, Md. E., Pal, A

Publication Details:Chem. Mater,2022, 34, 4456 - 4470

Abstract:
Supramolecular assemblies are essential for specific biological functions and mandate precise control over the mesoscopic scale for higher functional efficiency. Such well-defined biomimetic self-organization can be accessed through kinetically controlled nonequilibrium transformations rather than the typical downhill thermodynamically driven processes. Recently, spatiotemporal control for the living supramolecular polymerization has rendered a paradigm shift toward designing complex multicomponent supramolecular active materials; however, directing the active monomer toward predictive kinetically trapped materials still remains a considerable challenge as this necessitates circumventing spontaneous nucleation of the monomers during the self-assembly process. Herein, we demonstrate dual strategies (chemical and photo) to sequester the active peptide self-assembling motifs in dormant states that, upon judicious activation, engage in controlled seeded supramolecular polymerization in aqueous milieu for the first time. Amyloid-inspired peptide 1 with a pendant azobenzene moiety demonstrates the formation of on-pathway metastable nanoparticles by the interplay of solvent and temperature that could be transformed into kinetically controlled nanofibers and thermodynamically controlled twisted bundles. Further, using coupled equilibrium such as the host–guest inclusion complex with cyclodextrin or photoisomerization with UV light leads to the formation of two distinct off-pathway metastable states that retard the spontaneous supramolecular polymerization. A judicious manipulation of the free-energy landscapes in tandem with suitable chemical and photostimuli renders the activation of the dormant states for the peptide self-assembly through a seeded growth strategy. Finally, such photochemical sequestration of self-assembly pathways results in on–off piezoresponsive peptide nanostructures. In summary, we demonstrated for the first time the nonequilibrium peptide self-assembly coupled with dormant metastable states to allow access to an interesting repertoire of structural diversities and attenuated piezoresponse control in supramolecular peptide nanostructures.

DOI Link: 10.1021/acs.chemmater.2c00228