Significant Increase in the Dipole Moment of Graphene on Functionalization: DFT Calculations and Molecular Dynamics Simulations.

The limited solubility of graphene in water can be attributed to the existence of π-π bonds connecting its layers. Functionalized graphene or graphene oxide (GO) is frequently produced in order to overcome the shortcomings of graphene. Using density functional theory (DFT) calculation, functionalized graphene with various combinations of hydroxyl, epoxy, and carboxylic functional groups were investigated computationally. The study focused on the effects of functional group combinations on the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies, giving information about the chemical reactivity and stability of the molecules under investigation. Global chemical reactivity descriptors, including chemical hardness, softness, electronegativity, chemical potential, and electrophilicity index, were calculated to further elucidate the overall stability and reactivity of the molecules. The results demonstrated that the introduction of oxygen-containing functional groups on graphene significantly influenced its electronic properties, leading to variations in the chemical reactivity and stability. Molecular electrostatic potential (MEP) maps highlighted the susceptibility of specific regions to electrophilic and nucleophilic attacks. The flexibility and stability of functionalized graphene through root mean square fluctuation (RMSF) and root mean square deviation (RMSD) analyses indicate the stability of functionalized graphene in water. This comprehensive computational investigation provides valuable insights into the design and understanding of functionalized graphene for potential applications in drug delivery.

Imidazolium-Based Ionic Liquid-Assisted Silver Nanoparticles and Their Antibacterial Activity: Experimental and Density Functional Theory Studies.

The exclusive properties of ionic liquids (ILs) offer various opportunities to develop advanced materials with appreciable therapeutic applications. Imidazolium-based ILs have been frequently used as reaction media and stabilizers for the development and surface functionalization of noble metal nanoparticles (NPs). This study reports the citrate-mediated reduction of silver ions in three different ILs, that is, 1-ethyl-3-methylimidazolium methyl sulfate ([EMIM][MS]), 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([BMIM][OTf]), and 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([BMIM][TFSI]). The resulting Ag-ILs NPs were characterized using many analytical techniques, including UV-visible spectroscopy, dynamic light scattering (DLS), scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction (XRD). DLS and XRD characterization revealed the negatively charged Ag-[EMIM][MS] NPs, Ag-[BMIM][OTf] NPs, and Ag-[BMIM][TFSI] NPs with mean hydrodynamic sizes of 278, 316, and 279 nm, respectively, and a face-centered cubic structure. These hybrid nanomaterials were subjected to in vitro antibacterial screening against three bacterial strains. The Ag-[BMIM][OTf] NPs exhibited significant activities against Escherichia coli, Staphylococcus aureus, and Enterobacter cloacae. The lowest inhibition concentration of 62.5 µg/mL was recorded against E. coli using Ag-[EMIM][MS] and Ag-[BMIM][OTf] NPs. Further, the density functional theory calculations carried out on the computed Ag-ILs in the gas phase and water showed relatively stable systems. Ag-[BMIM][TFSI] exhibited the lowest Gibbs free energy change of -34.41 kcal/mol. The value of the global electrophilicity index (ω = 0.1865 eV) for the Ag-[BMIM][OTf] correlated with its good antibacterial activity.

Antimicrobial, antibiofilm, docking, DFT and molecular dynamics studies on click-derived isatin-thiosemicarbazone-1,2,3-triazoles.

In an effort to develop new antimicrobial and antibiofilm agents, we have designed and synthesized a novel class of isatin-thiosemicarbazone-1,2,3-triazoles through the CuAAC approach. All the synthesized hybrids were characterized by several spectral techniques such as FTIR, 1H NMR, 13C NMR, 2D NMR and HRMS. All the derivatives were evaluated for their antimicrobial and antibiofilm efficacy towards various microbial species. Triazole hybrid 8d exhibited the highest efficacy towards E. coli (MIC = 0.0067 µmol/mL) and S. aureus (MIC = 0.0067 µmol/mL), whereas, compounds 8b, 8c, 8d, 8e, 9a and terminal alkyne (10) significantly inhibited biofilm formation against S. aureus, B. subtilis and E. coli. To find out the structure-activity relationship and binding interactions of synthesized hybrids with enzymes 1KZN and 5TZ1, molecular docking for all the synthesized hybrids was carried out. DFT calculations for all hybrids and the molecular dynamics studies for compounds 9e and 9f were also performed to support the biological behavior of these hybrids.Communicated by Ramaswamy H. Sarma.

Click synthesis, antimicrobial, DNA photocleavage and computational studies of oxindole-tethered 1H-1,2,3-triazoles.

Aim: To obtain new hybrids derived from isatin and triazole. Materials & methods: A series of oxindole-1-H-1,2,3-triazole hybrids (4a-l) were synthesized from 3-sulfenylated N-propargylated oxindoles and organic azides employing Cu(I)-catalyzed azide-alkyne cycloaddition. These compounds were evaluated in vitro for antimicrobial activity by the standard serial dilution method and DNA photocleavage activity. Results: Antimicrobial assay revealed that compounds 4l and 4f exhibited promising efficacy against Candida albicans and Rhizopus oryzae, respectively, with a minimum inhibitory concentration value of 0.0008 µmol/mL. Compounds 4h and 4k completely degraded plasmid DNA. Further molecular docking of compounds with 1KZN (4j and 4k) and 5TZ1 (4h and 4l) revealed good binding interactions. Conclusion: Results of the current research can help in the development of new antimicrobial agents with high efficacy.

Comparative assessment of 9-bromo noscapine ionic liquid and noscapine: Synthesis, in-vitro studies plus computational & biophysical evaluation with human hemoglobin.

Noscapine is a proficient anticancer drug active against wide variety of tumors including lung cancer. Over time, several noscapine analogues have been assessed to maximize the efficiency of the drug, amongst which 9-bromo noscapine remains one of the most potent analogues till date. In the present work, we have synthesized 9-bromo noscapine ionic liquid [9-Br-Nos]IBr2, an active pharmaceutical ingredient based ionic liquid (API-IL) to address the existing issues of solubility and targeted drug delivery in the parent alkaloid as well as the synthesized analogues. We have devised a novel two-step synthesis route (first-ever ionic to ionic bromination) to obtain the desired [9-Br-Nos]IBr2 which is advantageous to its organic analogue in terms of increased solubility, lesser reaction time and better yield. Furthermore, we have compared 9-bromo noscapine ionic liquid with noscapine based on its binding interaction with human hemoglobin (Hb) studied via computational along with spectroscopic studies, and bioactivity against non-small cell lung cancer. We inferred formation of a complex between [9-Br-Nos]IBr2 and Hb in the stoichiometric ratio of 1:1, similar to noscapine. At 298 K, [9-Br-Nos]IBr2-Hb binding was found to exhibit Kb and ∆G of 36,307 M-1 and -11.5 KJmol-1, respectively, as compared to 159 M-1 and -12.5 KJmol-1 during Noscapine-Hb binding. This indicates a more stronger and viable interaction between [9-Br-Nos]IBr2 and Hb than the parent compound. From computational studies, the observed higher stability of [9-Br-Nos]I and better binding affinity with Hb with a binding energy of -91.75 kcalmol-1 supported the experimental observations. In the same light, novel [9-Br-Nos]IBr2 was found to exhibit an IC50 = 95.02 ± 6.32 µM compared to IC50 = 128.82 ± 2.87 µM for noscapine on A549 (non-small lung cancer) cell line at 48 h. Also, the desired ionic liquid proved to be more cytotoxic inducing a mortality rate of 87 % relative to 66 % evoked by noscapine at concentrations of 200 µM after 72 h.

Exploration of DFT and TD-DFT computation to investigate the interaction between paracetamol and lithium or its compounds.

Paracetamol is a commonly used antipyretic drug and its consumption drastically was increased during the COVID-19 times as fever was one of the symptoms. The excessive usage of paracetamol could harm humans, as the unused accumulated paracetamol can involve in the reaction with many small molecules as well as can interact with several biomolecules. Lithium chloride in its hydrated form is used as an antimanic drug and a geroprotector. It is needed in very small quantities by humans. Tetrahydrated form of lithium ion is the most stable hydrated form. Herein, the authors have investigated the interaction of paracetamol with tetrahydrated lithium chloride (1:1 and 1:2) using the DFT and TD-DFT calculations at 298 K and 310 K. The interaction of paracetamol with lithium chloride P1 (1:1), P2 (2:1), P3 (3:1) and P4 (4:1) are also studied by DFT calculations in default and CPCM model. The authors have calculated the free energy, optimization energy, dipole moment and other thermodynamic parameters of all the systems. Based on enthalpy and change in Gibbs free energy, the interaction was maximum between the paracetamol and tetrahydrated lithium chloride at 298 K as well as 310 K which indicates that the hydrated lithium chloride is being consumed by unused paracetamol. In P1 and P3, lithium showed interaction with oxygen of phenolic group and other atoms of all the paracetamol molecules present, while in P2 and P4, lithium showed these interactions with only one paracetamol molecule.

A review on recent advancements on removal of harmful metal/metal ions using graphene oxide: Experimental and theoretical approaches.

Graphene oxide is a two-dimensional carbon nanomaterial and has gained huge popularity over the last decade. Because, the graphene oxide can be dispersed in water easily and it is one of the most researched two-dimensional materials in the current time. The extraordinary properties shown by graphene oxide (GO) are due to its unique chemical structure; includes various hydrophilic functional groups containing oxygen such as carboxyl, hydroxyl, carbonyl and tiny sp2 carbon domains surrounded by sp3 domains. These groups are very peculiar for various applications as they allow covalent functionalisation with a plethora of compounds. Large surface area, intrinsic fluorescence, excellent surface functionality, amphiphilicity, improved conductivity, high adsorption capacity and superior biocompatibility are some of the chemical properties have drawn research from various fields. Graphene oxide has various interactions such as coordination, chelation, hydrogen bonding, electrostatic interaction, hydrophobic effects, π-π interaction, acid base interaction etc., with various metal ions. This review is focused on the removal of metals and metal ions due to their interactions mentioned above. Further, potential of composites of graphene oxide in the removal of metal and metal ions is also discussed. Further, the current challenges in this field at industrial-scale are also discussed.

An investigation for the interaction of gamma oryzanol with the Mpro of SARS-CoV-2 to combat COVID-19: DFT, molecular docking, ADME and molecular dynamics simulations.

COVID-19 has affected more or less every nation across the world and affected the economy very badly. Infection of this virus in human took the life of millions. We have already faced the first and the second waves of COVID-19 and recently, the nations or humanity is afraid of new strain, that is, OMICRON. Considered to highly infectious than the previous strains. Therefore, the researchers are working to find a promising molecule with no or permissible toxicity. In the present work, authors have chosen 10 molecules including the molecules used in curing the infection from nCoV. All the molecules were docked against Mpro of nCoV using iGemdock, a reliable computational tool. Based on the binding energy obtained, it can be seen that only latermovir; remdesivir; zanamivir showed better binding affinity than the gamma oryzanol, the molecule of interest in this work. These three molecules are already in use to cure the patients siffering from the infection of nCoV. But, we need a cost effective and easily available molecule to fight against this viral infection. The binding energy obtained for the formation of complex of gamma oryzanol with Mpro of nCoV through molecular docking is -118.787 kcal/mol. It forms conventional hydrogen bonds with the CYS145 (2.51 Å), LEU141 (3.01 Å) and SER144 (3.09 Å); forms C-H bonds with PHE140 (3.37 Å) and HIS163 (2.91 Å), forms alkyl interactions with ALA191 (3.59 and 4.74 Å), CYS145 (4.90 Å). One interesting information is obtained that the value of log Kp of gamma oryzanol is least means more permeable to skin in comparison of other molecules used in the work. Gamma oryzanol in known for to its biological potency like it can modulate the oxidative stress as well as inflammation. DFT calculations of gamma oryzanol (GO) was made at different temperature and no change in the delocalization of electron density as well no change in free energy is observed. Molecular dynamics (MD) simulations of gamma oryzanol with the Mpro of nCoV at different temperatures was performed. The formation of the complex between GO and Mpro of CoV at 290 K, 300 K, 310 K and 320 K for 100 ns was investigated. It has been observed that the effective binding is observed at 290 K, therefore, it can be said that the inhibition of the Mpro of nCoV with GO is maximum at 290 K.Communicated by Ramaswamy H. Sarma.

An understanding of coronavirus and exploring the molecular dynamics simulations to find promising candidates against the Mpro of nCoV to combat the COVID-19: A systematic review.

The first infection case of new coronavirus was reported at the end of 2019 and after then, the cases are reported in all nations across the world in a very short period. Further, the regular news of mutations in the virus has made life restricted with appropriate behavior. To date, a new strain (Omicron and its new subvariant Omicron XE) has brought fear amongst us due to a higher trajectory of increase in the number of cases. The researchers thus started giving attention to this viral infection and discovering drug-like candidates to cure the infections. Finding a drug for any viral infection is not an easy task and takes plenty of time. Therefore, computational chemistry/bioinformatics is followed to get promising molecules against viral infection. Molecular dynamics (MD) simulations are being explored to get drug candidates in a short period. The molecules are screened via molecular docking, which provides preliminary information which can be further verified by molecular dynamics (MD) simulations. To understand the change in structure, MD simulations generated several trajectories such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bonding, and radius of gyration for the main protease (Mpro) of the new coronavirus (nCoV) in the presence of small molecules. Additionally, change in free energy for the formation of complex of Mpro of nCoV with the small molecule can be determined by applying molecular mechanics with generalized born and surface area solvation (MM-GBSA). Thus, the promising molecules can be further explored for clinical trials to combat coronavirus disease-19 (COVID-19).

Hunting the main protease of SARS-CoV-2 by plitidepsin: Molecular docking and temperature-dependent molecular dynamics simulations.

COVID-19 has shaken all the countries across the globe and researchers are trying to find promising antiviral to cure the patients suffering from infection and can decrease the death. Even, different nations are using repurposing drugs to cure the symptoms and these repurposing drugs are hydroxychloroquine, remdesivir, and lopinavir, and recently, India has recently given the approval for the 2-deoxy-D-glucose for emergency purpose to cure the patients suffering from the COVID-19. Plitidepsin is a popular molecule and can be used in treatment of myeloma. Plitidepsin was explored by scientists experimentally against the COVID-19 and was given to the patient. It is found to be more a promising repurposing drug against the COVID-19 than the remdesivir. Therefore, there is a need to understand the interaction of plitidepsin with the main protease of SARS-CoV-2. Molecular docking of the plitidepsin against Mpro of SARS-CoV-2 was performed and the binding energy was found to be - 137.992 kcal/mol. Furthermore, authors have performed the molecular dynamics simulations of the main protease of SARS-CoV-2 in presence of plitidepsin at 300 and 325 K. It was found that the plitidepsin binds effectively with the main protease of SARS-CoV-2 at 300 K.