Orchestration of ferro- and anti-ferromagnetic ordering in gold nanoclusters.

The unpaired electron in the gold clusters (Aun, n = no. of Au atoms) with an odd number of total electrons is solely responsible for the magnetic properties in the small-sized Au nano-clusters. However, no such unpaired electron is available due to pairing in the even number of atom gold clusters and behaving as a diamagnetic entity similar to bulk gold. In this work, we unveiled the spin-density distribution of odd Aun clusters with n = 1 to 19 that reveals that a single unpaired electron gets distributed non-uniformly among all Au-atoms depending on the cluster size and morphology. The delocalization of the unpaired electron leads to the spin dilution approaching a value of ∼1/n spin moments on each atom for the higher clusters. Interestingly, small odd-numbered gold clusters possess spin-magnetic moments similar to the delocalized spin moments as of organic radicals. Can cooperative magnetic properties be obtained by coupling these individual magnetic gold nanoparticles? In this work, by applying state-of-the-art computational methodologies, we have demonstrated ferromagnetic or anti-ferromagnetic couplings between such magnetic nanoclusters upon designing suitable organic spacers. These findings will open up a new avenue of nanoscale magnetic materials combining organic spacers and odd-electron nano-clusters.

Unravelling the Highest Magnetic Anisotropy Among all the nd-Shells in [WCp2]0 Metallocene.

Single-molecule magnets (SMMs) with a large magnetization reversal barrier are predominated by the lanthanide systems due to their strong spin-orbit coupling (SOC). However, the transition metals have also emerged as potential contenders and the largest magnetic anisotropy has been identified for a cobalt system among any d-series-based SMMs (Bunting et al. Science 2018, 362, eaat7319). In this work, we have explored the magnetic anisotropy in highly axial ligand field systems of metallocene, having different d-subshell (3d4, 4d4, and 5d4). The wave function-based multireference methods including static and dynamic electron correlations have been employed to investigate the zero-field splitting (ZFS) parameters. Here, we report exceptionally large magnetic anisotropy for a 5d complex of [WCp2]0 with the highest energy barrier that is nearly twice as high as the previous record value for the Co complex. We have also observed that the axial ZFS parameter (D) is increasing down the group in the order of 3d < 4d < 5d, pertaining to a large SOC.

Can Iron-Porphyrins Behave as Single-Molecule Magnets?

The study of magnetic properties, especially the magnetic anisotropy of iron-porphyrin complexes employing multiconfigurational methods, is quite challenging due to many strongly correlated electrons in nearly degenerate orbitals. However, a prerequisite for observing the magnetic anisotropy and slow magnetization relaxation, the zero-field splitting parameter, D, was experimentally observed decades ago for halide-based axially ligated penta-coordinate Fe(III)-porphyrins. In these complexes, the signs of D were reported mostly as positive; in a few cases, inconclusive signs of the D parameter were also mentioned. However, no ab initio calculations have been reported to shed light on this. Deciphering the electronic structure of these penta-coordinated complexes employing the complete active space self-consistent field method and N-electron valence second-order perturbation theory, we confirm the positive D values. However, a negative D value is highly desired to observe the single-molecule magnet properties without an external magnetic field, which we observed in the Fe(II)-porphyrin complexes with axial imidazole ligands instead of halide ligands. The detailed analysis of the multireference wave functions unravels the role of axial ligands in determining the sign and magnitude of the D parameters.

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

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.

High-Spin Blatter's Triradicals.

Robust organic triradicals with high-spin quartet ground states provide promising applications in molecular magnets, spintronics, etc. In this context, a triradical based on Blatter's radical has been synthesized recently, having two low-lying non-degenerate doublet states with a quartet ground state. The traditional broken-symmetry (BS)-DFT computed doublet-quartet energy gaps are reported to be somewhat overestimated in comparison to the experimentally observed values. In this work, we have employed different ab initio methods on this prototypical system to obtain more accurate doublet-quartet energy gaps for this triradical. The spin-constraint broken-symmetry (CBS)-DFT method has been used to reduce the overestimation of energy gaps from BS-DFT. To address the issues of spin-contamination and the multireference nature of low-spin states affecting the DFT methods, we have computed the energy gaps using appropriately state-averaged CASSCF and NEVPT2 computations. Using a series of active spaces, our calculations are shown to provide quite accurate values in concordance with the experimentally observed results. Furthermore, we have proposed and modeled another two triradicals based on Blatter's radical, which are of interest for experimental synthesis and characterization. Our computations show that all these triradicals also have a quartet ground state with a similar energy difference between the excited doublet states.

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

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.

Anti-ohmic nanoconductors: myth, reality and promise.

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.

Development of nanostructured lipid carriers as a promising tool for methotrexate delivery: physicochemical and in vitro evaluation.

The aim of the present study is to fabricate the stable nanostructured lipid carriers (NLCs) using biocompatible excipients for the encapsulation of Methotrexate (MTX), a chemotherapeutic agent for breast cancer treatment. MTX has restricted clinical applications owing to its low solubility, non-specific targeting and adverse side effects. Glyceryl Monostearate (GMS) and Miglyol 812 (MI1) were chosen as solid and liquid lipids, respectively, for the fabrication of NLCs, and the influence of variation of solid and liquid composition was investigated. The prepared NLCs exhibited long-term stability and spherical shape morphology as characterized by electron microscopy. The internal structure of fabricated NLCs was arranged into cubic crystalline as confirmed by small-angle X-ray scattering (SAXS) analysis. MTX's encapsulation efficiency of ∼85 ± 0.9%. and sustained in vitro release of MTX ∼ 52% ± 3.0 in 24 h was achieved. Classical molecular dynamics (MD) simulations were performed to study the structural stability of the MTX encapsulated NLCs. Hemolysis carried out on the NLCs showcased the biosafety of the formulation under the tolerance limit (<10%). Further, the MTT assay demonstrates that MTX-loaded NLCs exhibited toxicity against HeLa and MCF-7 cell lines as compared to blank NLCs. The finding demonstrates NLCs as promising vehicles for MTX delivery to address cancer.Communicated by Ramaswamy H. Sarma.

How do the mutations in PfK13 protein promote anti-malarial drug resistance?

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.Communicated by Ramaswamy H. Sarma.

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

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.

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

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.

α-Helix in Cystathionine ß-Synthase Enzyme Acts as an Electron Reservoir.

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 ß-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.

The influence of the radicaloid character of polyaromatic hydrocarbon couplers on magnetic exchange interactions.

The molecular properties of conjugated spacers, such as the π-conjugation, aromaticity, length of the couplers, etc., that couple two localized spin-centers influence the intramolecular magnetic exchange interactions (2J) mediated through them. In recent years, the development and synthesis of highly conjugated polyaromatic hydrocarbons (PAHs) in the context of graphene nano-ribbon carbonaceous materials, prompted us to investigate their role as magnetic couplers. Apart from the highly conjugated nature of various PAHs, the intriguing open-shell characteristic dominates the electronic structures and properties of the PAHs. The extent of the open-shell behaviors of the PAHs could be quantified with the radicaloid character (y) applying density functional theory (DFT) calculations. In this work, we observed a strong correlation between the radicaloid character of the spacer and the strength of the magnetic exchange interactions mediated through it. The larger the radicaloid character the stronger the magnetic exchange interactions within the fixed length of the couplers.

Harnessing Colossal Magnetic Anisotropy in Sandwiched 3d2-Metallocenes.

Single-molecule magnets are gaining attention in recent years with the growing focus on achieving higher barriers of magnetization reversal. Metallocenes, owing to their unique sandwiched structure, assure themselves as plausible molecular systems for the development of novel single-molecule magnets (SMMs). Here in this work, we have explicitly investigated metallocenes of first-row transition elements, along with their one-electron-oxidized (cationic) and -reduced (anionic) analogues, for their magnetic anisotropies by adopting multireference ab initio calculations. Herein, we report a high magnetic anisotropy for 3d2 systems among all 3d-metallocenes.

Photoexcited Intramolecular Charge Transfer in Dye Sensitizers: Predictive In Silico Screening for Dye-Sensitized Solar Cell Devices.

Efficient photoinduced intramolecular charge transfer (ICT) from donor to acceptor in dye molecules is the functional basis and key property in the working of a dye-sensitized solar cell (DSSC). To understand the ICT process in photoexcited dye molecules, we analyze the electronic properties and structural parameters of a chosen set of experimentally synthesized donor-acceptor (D-A) and donor-π-spacer-acceptor (D-π-A) type dye molecules in their ground, excited, and cationic states. The correlation between structural modification and charge redistribution in different parts of the molecule helps to identify the extent of π-conjugation and spatial rearrangement of electron density localization along the molecular skeleton. We find that prominent twisting of several groups and the resulting molecular bond rearrangements in larger parts of the molecule promote efficient donor to acceptor ICT, such as in D-A type ADEKA1 and C275 dyes. Thus, based on the modest computation of structural and electronic properties of dye molecules in their respective ground, excited, and cationic states, we identify the desired structural changes that facilitate tunable intramolecular charge transfer to highlight a simple and direct prescription to screen out probable efficient dye molecules among many samples. Our approach complements recent experimental evidence of capturing the structural view of the excited-state charge transfer in molecules.

Tuning the magnetic properties of a diamagnetic di-Blatter's zwitterion to antiferro- and ferromagnetically coupled diradicals.

In the quest of obtaining organic molecular magnets based on stable diradicals, we have tuned the inherent zwitterionic ground state of tetraphenylhexaazaanthracene (TPHA), a molecule containing two Blatter's moieties, by adopting two different strategies. In the first strategy, we have increased the length of the coupler between the two radical moieties and observed a transition from the zwitterionic ground state to the diradicalized state. With a larger coupler, ferromagnetic interactions are realized based on density functional theory (DFT) and wave-function theory (WFT) based complete active space self-consistent field (CASSCF)-N-electron valence state perturbation theory (NEVPT2) methods. An analysis based on the extent of spin contamination, diradical character, CASSCF orbital occupation number, Head-Gordon's index, HOMO-LUMO and SOMOs energy gaps is demonstrated that marks the transition of the ground state in these systems. In another approach, we systematically explore the effect of push-pull substitution on the way to obtain molecules based on a TPHA skeleton with diradicaloid state and, in some cases, even a triplet ground state.

Understanding the role of R266K mutation in cystathionine ß-synthase (CBS) enzyme: an in silico study.

Human cystathionine ß-synthase (hCBS) is a Heme-containing, unique pyridoxal 5'-phosphate (PLP) dependent enzyme. CBS catalyzes the bio-chemical condensation reactions in the transsulfuration pathway. The role of Heme in the catalytic activities of the hCBS enzyme is still unknown, even though various experimental studies indicated its participation in the bi-directional electronic communication with the PLP center. The hypothesis is, Heme acts as an electron density reservoir for the catalytic reaction center rather than a redox electron source. In this work, we have investigated In Silico dynamical aspects of the bi-directional communications by performing classical molecular dynamics (MD) simulations upon developing the necessary force field parameters for the cysteine and histidine bound hexa-coordinated Heme. The comparative aspects, of electron density overlap across the communicating pathways, were investigated adopting the Density Functional Theory (DFT) in conjunction with the hybrid exchange-correlation functional for the CBSWT (wild-type) and CBSR266K (mutated) enzymes. The molecular dynamics simulations and subsequent explorations of the electronic structures confirm the reported observations. It also provides an in-depth mechanistic understanding of how the non-covalent hydrogen bonding interactions with Cys52 control such long-distance communication. Our study also provides a convincing answer to the reduced enzymatic activities in the R266K mutated hCBS compared to the wild-type enzymes. The difference in hydrogen-bonding patterns and salt-bridge interactions play the pivotal roles in such long distant bi-directional communications.Communicated by Ramaswamy H. Sarma.

Auxiliary Atomic Relay Center Facilitates Enhanced Magnetic Couplings in Blatter's Radical.

The recent accomplishments in obtaining strong ferromagnetic exchange interactions in organic diradicals have made the field quite fascinating and even more promising toward its technological applications. In this context, herein, we report a unique combination of remarkably strong ferromagnetic exchange interactions coupled with molecular rigidity, utilizing superstable Blatter's radical as a spin source. The planar analogues of the parent Blatter's radical obtained by annulation with a chalcogen coupled to nitronyl nitroxide (NN) are investigated using density functional theory along with the wave function-based multiconfigurational self-consistent field methods, for example, complete active space self-consistent field (CASSCF)-N-electron valence state perturbation theory (NEVPT2). The calculations reveal phenomenal modulation in exchange couplings upon annulation such that remarkably strong ferromagnetic interactions are realized especially for a certain class of the Blatter-NN diradicals. The modulation of spin-spin interactions is rationalized by variation in spin density distribution and molecular torsional angles. We demonstrate that annulation in OMMs opens an additional coupling pathway via auxiliary X-atom acting as the atomic relay center which strongly manipulates the magnitude of exchange couplings.

First-Principles Investigations of Magnetic Anisotropy and Spin-Crossover Behavior of Fe(III)-TBP Complexes.

With the ongoing effort to obtain mononuclear 3d-transition-metal complexes that manifest slow relaxation of magnetization and, hence, can behave as single-molecule magnets (SMMs), we have modeled 14 Fe(III) complexes based on an experimentally synthesized (PMe3)2FeCl3 complex [J. Am. Chem. Soc. 2017, 139 (46), 16474-16477], by varying the axial ligands with group XV elements (N, P, and As) and equatorial halide ligands from F, Cl, Br, and I. Out of these, nine complexes possess large zero field splitting (ZFS) parameter D in the range of -40 to -60 cm-1. The first-principles investigation of the ground-spin state applying density functional theory (DFT) and wave function-based multiconfigurations methods, e.g., SA-CASSCF/NEVPT2, are found to be quite consistent except for few delicate cases with near-degenerate spin states. In such cases, the hybrid B3LYP functional is found to be biased toward high-spin (HS) state. Altering the percentage of exact exchange admixed in the B3LYP functional leads to intermediate-spin (IS) ground state consistent with the multireference calculations. The origin of large zero field splitting (ZFS) in the Fe(III)-based trigonal bipyramidal (TBP) complexes is investigated. Furthermore, a number of complexes are identified with very small ΔGHS-ISadia. values indicating the possible spin-crossover phenomenon between the bistable spin states.