Density Functional Calculations
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Adsorption of cell-penetrating peptides (CPPs) at cellular membranes is the first and necessary step for their subsequent translocation across cellular membranes into the cytosol. It has been experimentally shown that CPPs rich in arginine (Arg) amino acid penetrate across phospholipid bilayers more effectively than their lysine (Lys) rich counterparts. In this work, we aim to understand the differences in the first translocation step, adsorption of Arg9 and Lys9 peptides at fully hydrated neutral phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipid bilayers and evaluate in detail the energetics of the process using molecular dynamics (MD) simulations and free energy calculations of adsorption of the single peptide. We show that the adsorption of Arg9 is energetically feasible, with the free energy of adsorption being ∼-5.0 kcal mol-1 at PC and ∼-5.5 kcal mol-1 at PE bilayers. In contrast, adsorption of Lys9 is not observed at PC bilayers, and their adsorption at PE bilayers is very weak, being ∼-0.5 kcal mol-1. We show by energy decomposition and analysis of peptide hydration along the membrane that significantly stronger electrostatic interactions of Arg9 with lipid phosphate groups, together with the greater loss of peptide hydration (and in turn stronger hydrophobic interactions) along the membrane translocation path, are the main driving factors governing the adsorption of Arg-rich peptides at neutral lipid bilayers in contrast to Lys-rich peptides. Finally, we also compare the energetics in lipid/bilayer systems with the density functional theory (DFT) calculations of the corresponding model systems in the continuum water model and reveal the energetic differences in different environments.
- MeSH
- fosfatidylcholiny chemie MeSH
- fosfolipidy MeSH
- lipidové dvojvrstvy chemie MeSH
- penetrační peptidy * chemie MeSH
- polylysin * MeSH
- simulace molekulární dynamiky MeSH
- teorie funkcionálu hustoty MeSH
- termodynamika MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fosfatidylcholiny MeSH
- fosfolipidy MeSH
- lipidové dvojvrstvy MeSH
- penetrační peptidy * MeSH
- polyarginine MeSH Prohlížeč
- polylysin * MeSH
This study explores the structural and electronic factors affecting the absorption spectra of 5-carboxy-tetramethylrhodamine (TAMRA) in water, a widely used fluorophore in imaging and molecular labeling in biophysical studies. Through molecular dynamics (MD) simulations and density functional theory (DFT) calculations, we examine TAMRA UV absorption spectra together with TAMRA-labeled peptides (Arg9, Arg4, Lys9). We found that DFT calculations with different functionals underestimate TAMRA maximum UV absorption peak by ~100 nm, resulting in the maximum at ca. 450 nm instead of the experimental value of ca. 550 nm. However, incorporating MD simulation snapshots of TAMRA in water, the UV maximum peak shifts and is in close agreement with the experimental results due to the rotation of TAMRA N(CH3)2 groups, effectively captured in MD simulations. The method is used to estimate the UV absorption spectra of TAMRA-labeled peptides, matching experimental values.
- Klíčová slova
- UV absorption spectra, fluorescent probes, molecular dynamics simulations, time‐dependent density functional theory,
- MeSH
- fluorescenční barviva * chemie MeSH
- peptidy * chemie MeSH
- rhodaminy * chemie MeSH
- simulace molekulární dynamiky * MeSH
- spektrofotometrie ultrafialová MeSH
- teorie funkcionálu hustoty * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fluorescenční barviva * MeSH
- peptidy * MeSH
- rhodaminy * MeSH
- tetramethylrhodamine MeSH Prohlížeč
We use real-time density functional theory on a real-space grid to calculate electronic excitations of bacteriochlorophyll chromophores of the light-harvesting complex 2 (LH2). Comparison with Gaussian basis set calculations allows us to assess the numerical trust range for computing electron dynamics in coupled chromophores with both types of techniques. Tuned range-separated hybrid calculations for one bacteriochlorophyll as well as two coupled ones are used as a reference against which we compare results from the adiabatic time-dependent local density approximation (TDLDA). The tuned range-separated hybrid calculations lead to a qualitatively correct description of the electronic excitations and couplings. They allow us to identify spurious charge-transfer excitations that are obtained with the TDLDA. When we take into account the environment that the LH2 protein complex forms for the bacteriochlorophylls, we find that it substantially shifts the energy of the spurious charge-transfer excitations, restoring a qualitatively correct electronic coupling of the dominant excitations also for TDLDA.
In this study, a functionalized graphene oxide-cerium oxide nanocatalysts (FGCe) with varying graphene oxide (GO) contents were prepared using an in-situ reflux method. The prepared nanocatalysts showcased improvement in the crystallinity and BET surface area values with increasing GO contents. The efficacies of prepared catalysts were investigated towards oxidative pyrolysis of alkali lignin in an ethanol-water system. Among various nanocatalyst samples, the best lignin conversion (93 %) and bio-oil yield (86 %) were achieved using 50 mg FGCe nanocatalyst (0.5 wt% GO) at 423 K and 60 min. GC-MS and 1HNMR analyses were used to identify significant lignin conversion products, including 2-pentanone-4-hydroxy-4-methyl, 2-methoxyphenol, nonylcyclopropane, vanillin, apocynin, homovanollic acid, and benzoic acid. Kinetic studies revealed that the activation energy for lignin conversion was 24.36 kJ/mol at 423 K. Mechanistic investigations by density functional theory analysis revealed that the lignin breakdown occurred at oxygen bonds producing aromatic.
- Klíčová slova
- Alkali lignin, Cerium oxide, Density functional theory, Functionalized graphene oxide, Pyrolysis,
- MeSH
- alkálie * chemie MeSH
- cer * chemie MeSH
- dusík * chemie MeSH
- grafit * chemie MeSH
- katalýza MeSH
- kinetika MeSH
- lignin * chemie MeSH
- oleje rostlin MeSH
- oxidace-redukce MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- polyfenoly MeSH
- pyrolýza * MeSH
- teorie funkcionálu hustoty MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alkálie * MeSH
- Bio-Oil MeSH Prohlížeč
- cer * MeSH
- ceric oxide MeSH Prohlížeč
- dusík * MeSH
- grafit * MeSH
- graphene oxide MeSH Prohlížeč
- lignin * MeSH
- oleje rostlin MeSH
- polyfenoly MeSH
AIMS: The aim of the present research was to synthesize glycoluril derivative 2,4-Bis(4- cyanobenzyl)glycoluril through a convergent scheme. BACKGROUND: For this purpose, Sandmeyer reaction procedure was employed for the synthesis of said compound. The structure of the pure compound was confirmed by using different spectroscopic techniques, such as 1HNMR, 13C-NMR and (HR-MS) Mass spectrometry. OBJECTIVE: Convergent synthesis of 2,4-BIS (4-CYANOBENZYL)GLYCOLURIL USING SANDMEYER REACTION and urease inhibition study. METHODS: The structure of the pure compound was confirmed by using different spectroscopic techniques such as 1H-NMR, 13C-NMR and (HR-MS) Mass spectrometry. The electronic properties of the newly synthesized compound and thiourea were determined by using density functional theory. RESULTS: Furthermore, the compound was evaluated against urease enzyme and was found to be potent inhibitors with an IC50 value of 11.5 ± 1.50 μM when compared with standard inhibitor thiourea (IC50 = 21.0 ± 1.90 μM). The compound may serve as a lead compound to synthesize new cyano-based bambusuril in the future with enhanced biological properties. CONCLUSION: We have synthesized a new glycoluril derivative 2,4-Bis(4-cyanobenzyl)glycoluril by the sandmeyer reaction. It has been obtained in the form of light yellowish powder in good yield (96%). Glycoluril based macrocycles have been used in various fields; starting from the 2,4-Bis(4-nitrobenzyl)glycoluril (already reported compound), which has undergone reduction (CH3OH,Pt/C) , diazotization (NaNO2/HCl), cyanation (CuCl/KCN), respectively in order to synthesize the desired new glycoluril derivative. The obtained product will be used as a building block for the synthesis of the cyano based bambusuril marcocycle in the future. The yield of the obtained product has been monitored by using different amounts of cyanating reagent, but the best results are shown by the use of 4 mmol of CuCl/KCN. KCN with CuCl assisted the conversion of diazo group into the cyano group with enhanced yield when used in excess amount. It acts as a catalyst. The solubility characteristic of 2,4-Bis(4-cyanobenzyl)glycoluril has also been determined in different organic solvents. 1H NMR technique proved to be very helpful for the structure determination of our desired product. Benzylic protons give signals at 7.5 ppm and 7.8 ppm, respectively. The downfield peaks confirm the presence of CN group near the benzylic protons. Methine protons show a signal at 5.2 ppm, which ensures the basic skeleton of glycoluril. Ureidyl protons also confirm the synthesis of the heterocyclic 2,4-Bis(4-cyanobenzyl)glycoluril compound. The negative and positive electrostatic potential sites, molecular descriptors, and charge density distribution of frontier molecular orbitals are revealing that 4a with promising sites for electrophilic and nucleophilic attacks would result to enhance the urease inhibition, which is in good agreement with the experimental data.
- Klíčová slova
- (HR-MS) mass spectrometry, 1H NMR, Glycoluril derivative, IC50, bambusuril., density functional theory (DFT), sandmeyer reaction, thiourea, urease enzyme,
- MeSH
- imidazoly MeSH
- inhibitory enzymů * farmakologie MeSH
- simulace molekulového dockingu MeSH
- teorie funkcionálu hustoty MeSH
- ureasa * metabolismus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- glycoluril MeSH Prohlížeč
- imidazoly MeSH
- inhibitory enzymů * MeSH
- ureasa * MeSH
An increasing number of products containing synthetic cannabinoids pose a growing crisis to public health worldwide. Recently, a rising number of cases of serious adverse health effects, intoxications, and death cases associated with synthetic cannabinoids were reported. The current study represents the comprehensive structural analysis of three new synthetic cannabinoids (AB-, ADB- and AMB-FUBINACA) in solution investigated by electronic and vibrational circular dichroism together with the conventional methods of infrared and ultraviolet absorption spectroscopy, all supported by the density functional theory (DFT) calculations. The best level of theory to reproduce the experimental wavenumbers and wavelengths was found to be the B3PW91 method with a 6-311++G(d,p) basis set including the implicit solvent effect simulation. Very good agreement between the experimental and simulated spectra allowed us to determine the absolute configuration and a detailed interpretation of the IR absorption, VCD, ECD and UV spectra of AB-, ADB- and AMB-FUBINACA. In addition, the HOMO and LUMO electronic transitions were calculated.
- Klíčová slova
- Chiroptical spectroscopy, DFT calculation, Drugs, Synthetic cannabinoids, Vibrational spectroscopy,
- MeSH
- cirkulární dichroismus MeSH
- kanabinoidy * MeSH
- teorie funkcionálu hustoty MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kanabinoidy * MeSH
Cyclic dinucleotides (CDNs) are important second messengers in bacteria and eukaryotes. Detailed characterization of their physicochemical properties is a prerequisite for understanding their biological functions. Herein, we examine acid-base and electromigration properties of selected CDNs employing capillary electrophoresis (CE), density functional theory (DFT), and nuclear magnetic resonance (NMR) spectroscopy to provide benchmark pKa values, as well as to unambiguously determine the protonation sites. Acidity constants (pKa) of the NH+ moieties of adenine and guanine bases and actual and limiting ionic mobilities of CDNs were determined by nonlinear regression analysis of the pH dependence of their effective electrophoretic mobilities measured by CE in aqueous background electrolytes in a wide pH range (0.98-11.48), at constant temperature (25°C), and constant ionic strength (25 mM). The thermodynamic pKa values were found to be in the range 3.31-4.56 for adenine and 2.28-3.61 for guanine bases, whereas the pKa of enol group of guanine base was in the range 10.21-10.40. Except for systematic shifts of ∼2 pKa, the pKa values calculated by the DFT-D3//COSMO-RS composite protocol that included large-scale conformational sampling and "cross-morphing" were in a relatively good agreement with the pKas determined by CE and predict N1 atom of adenine and N7 atom of guanine as the protonation sites. The protonation of the N1 atom of adenine and N7 atom of guanine in acidic background electrolytes (BGEs) and the dissociation of the enol group of guanine in alkaline BGEs was confirmed also by NMR spectroscopy.
- Klíčová slova
- DFT calculations, NMR spectroscopy, acidity constant, capillary electrophoresis, cyclic dinucleotides,
- MeSH
- dinukleosidfosfáty chemie MeSH
- elektroforéza kapilární * metody MeSH
- koncentrace vodíkových iontů MeSH
- magnetická rezonanční spektroskopie * metody MeSH
- protony * MeSH
- teorie funkcionálu hustoty MeSH
- termodynamika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dinukleosidfosfáty MeSH
- protony * MeSH
This study provides a comprehensive investigation of the structural and vibrational properties of protonated cytosine monomers and dimers. Experimental IRPD spectroscopy, combined with theoretical calculations, revealed distinct behaviors for monomers and dimers. We find that protonated cytosine monomers predominantly adopt the enol form in the gas phase, with a contribution from the keto form between 25% and 33%. For dimers, our computations predict a keto-enol configuration to be more stable than the keto-keto form by 1.5 kcal mol-1. However, experimentally, the keto-keto form emerged as the dominant structure. The theoretically most stable keto-enol configuration undergoes a structural reorganization in MD simulations with explicit methanol, forming the dynamically unstable neutral-keto-protonated-keto complex. This reorganization highlights the role of environmental factors in modulating tautomer populations.
- MeSH
- cytosin * chemie MeSH
- dimerizace MeSH
- DNA * chemie MeSH
- simulace molekulární dynamiky MeSH
- spektrofotometrie infračervená MeSH
- teorie funkcionálu hustoty MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cytosin * MeSH
- DNA * MeSH
A biomimetic approach to the formation of titania (TiO2) nanostructures is desirable because of the mild conditions required in this form of production. We have identified a series of serine-lysine peptides as candidates for the biomimetic production of TiO2 nanostructures. We have assayed these peptides for TiO2-precipitating activity upon exposure to titanium bis(ammonium lactato)dihydroxide and have characterized the resulting coprecipitates using scanning electron microscopy. A subset of these assayed peptides efficiently facilitates the production of TiO2 nanospheres. Here, we investigate the process of TiO2 nanosphere formation mediated by the S-K peptides KSSKK- and SKSK3SKS using one-dimensional and two-dimensional solid-state NMR (ssNMR) on peptide samples with uniformly 13C-enriched residues. ssNMR is used to assign 13C chemical shifts (CSs) site-specifically in each free peptide and TiO2-embedded peptide, which are used to derive secondary structures in the neat and TiO2 coprecipitated states. The backbone 13C CSs are used to assess secondary structural changes undergone during the coprecipitation process. Side-chain 13C CS changes are analyzed with density functional theory calculations and used to determine side-chain conformational changes that occur upon coprecipitation with TiO2 and to determine surface orientation of lysine side chains in TiO2-peptide composites.
- MeSH
- lysin chemie MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulární modely MeSH
- oxid křemičitý chemie MeSH
- peptidy chemie MeSH
- sekundární struktura proteinů MeSH
- sekvence aminokyselin MeSH
- serin chemie MeSH
- teorie funkcionálu hustoty * MeSH
- titan chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- lysin MeSH
- oxid křemičitý MeSH
- peptidy MeSH
- serin MeSH
- titan MeSH
- titanium dioxide MeSH Prohlížeč
Platinum-based anticancer drugs are actively developed utilizing lipophilic ligands or drug carriers for the efficient penetration of biomembranes, reduction of side effects, and tumor targeting. We report the development of a supramolecular host-guest system built on cationic platinum(II) compounds bearing ligands anchored in the cavity of the macrocyclic host. The host-guest binding and hydrolysis process on the platinum core were investigated in detail by using NMR, MS, X-ray diffraction, and relativistic DFT calculations. The encapsulation process in cucurbit[7]uril unequivocally promotes the stability of hydrolyzed dicationic cis-[PtII(NH3)2(H2O)(NH2-R)]2+ compared to its trans isomer. Biological screening on the ovarian cancer lines A2780 and A2780/CP shows time-dependent toxicity. Notably, the reported complex and its β-cyclodextrin (β-CD) assembly achieve the same cellular uptake as cisplatin and cisplatin@β-CD, respectively, while maintaining a significantly lower toxicity profile.
- MeSH
- lidé MeSH
- makrocyklické sloučeniny chemická syntéza chemie farmakologie MeSH
- makromolekulární látky chemická syntéza chemie farmakologie MeSH
- molekulární struktura MeSH
- nádorové buňky kultivované MeSH
- organoplatinové sloučeniny chemická syntéza chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky chemická syntéza chemie farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- teorie funkcionálu hustoty * MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- makrocyklické sloučeniny MeSH
- makromolekulární látky MeSH
- organoplatinové sloučeniny MeSH
- protinádorové látky MeSH
