Increased Van Der Waals Interactions Research Articles

Terminal methylene biphenyl derived coumarin Schiff base-esters: Synthesis, mesomorphic behaviour and DFT investigations

In the present investigation new unsymmetrical coumarin-methylene biphenyl MBPCE-(2–16) mesogens were designed and synthesized. Methylene biphenyl end group at one end of molecules have been linked to the 7-alkyloxy substituted coumarin core through imine and ester mesogenic connecting units. The structures of new hybrids have been elucidated employing different analytical techniques including FT-IR, 1H NMR, 13C NMR, Mass & CHN elemental analysis. New molecules have been investigated for their mesomorphic behaviour using DSC (Measurement of transition temperature and enthalpy associated) and POM (Texture study) techniques and the existence of mesophase was established by VT-XRD analysis. Compounds with n = 2 (-OC2H5) to n = 7 (-OC7H15) chain length exhibited enantiotropic nematic mesophase with good thermal stability. As the chain length increases, compounds from n = 8 (-OC8H17) and n = 10 (-OC10H21) displayed enantiotropic nematic as well as smectic-A mesophase whereas compound with n = 12 (-OC12H25) showed only interdigitated SmA phase. Next two members of the series failed to show any mesomorphism. The commencement of SmA phase and disappearance of nematic could be attributed to more layer arrangement with increased van der waals interactions. The density functional theory (DFT) calculations were employed to complement the experimental results concerning the mesomorphic behaviour. Development of smectic phase could be due to the augmentation in the area of the intermolecular interaction which increases the degree of molecular packing. Conversely, it was discovered that higher polarizability leads to lower nematic thermal stability because it strengthens parallel intermolecular interactions, which promotes a higher degree of molecular order while reducing the development of lower-order nematic mesophase.

Superalkali nature of the Si9M5 (M = Li, Na, and K) Zintl clusters: a theoretical study on electronic structure and dynamic nonlinear optical properties.

Zintl clusters have attracted widespread attention because of their intriguing bonding and unusual physical properties. We explore the Si9 and Si9M5 (where M = Li, Na, and K) Zintl clusters using the density functional theory combined with other methods. The exothermic nature of the Si9M5 cluster formation is disclosed, and the interactions of alkali metals with pristine Si9 are shown to be noncovalent. The reduced density gradient analysis is performed, in which increased van der Waals interactions are observed with the enlargement of the size of alkali metals. The influence of the implicit solvent model is considered, where the hyperpolarizability (βo) in the solvent is found to be about 83 times larger than that in the gas phase for Si9K5. The frequency-dependent nonlinear optical (NLO) response for the dc-Kerr effect is observed up to 1.3 × 1011 au, indicating an excellent change in refractive index by an externally applied electric field. In addition, natural bonding orbitals obtained from the second-order perturbation analysis show the charge transfer with the donor-acceptor orbitals. Electron localization function and localized orbital locator analyses are also performed to better understand the bonding electrons in designed clusters. The studied Zintl clusters demonstrate the superalkali character in addition to their remarkable optical and nonlinear optical properties.

Reconsideration about the competitive adsorption of H2O and CO2 on carbon surfaces: The influence of oxygen functional groups

The primary challenge that hampers the widespread use of carbon-based adsorbents for CO2 storage is their low adsorption efficiency. There has been a disagreement among researchers regarding how H2O influences CO2 adsorption in these adsorbents. To address this, a detailed study was conducted by density functional theory and adsorption experiments. The adsorption of CO2 by H2O was examined on carbon surfaces modified with different oxygen functional groups at the molecular level. The results demonstrated that carboxyl and hydroxyl groups, improved the polarity of the carbon surfaces. This enhancement facilitated the adsorption of CO2. The introduction of carboxyl groups increased van der Waals interactions between the carbon surface and CO2, while the introduction of hydroxyl groups facilitated the formation of hydrogen bonds between hydroxyl and CO2. These interactions stabilized the adsorption configuration of CO2. Since the local polarity of H2O exceeds that of CO2, H2O preferentially adsorbs, potentially occupying the adsorption site of CO2. Furthermore, the van der Waals interaction formed between H2O and CO2 might impede CO2 adsorption, thereby reducing co-adsorption energy. The experimental results align with the simulation outcomes. This study presents a novel approach for developing carbon-based adsorbents that efficiently capture CO2 under wet conditions.

Comparative study on adsorption of volatile organic compounds on graphene, boron nitride and boron carbon nitride nanosheets

This computational study explores the adsorption of volatile organic compounds (VOCs), namely 1,3-butadiene, benzene, indole and toluene, using graphene (GRA), boron nitride (BN) and boron carbon nitride (BCN) nanosheets. The optimized structures obtained from the density functional theory computations and their vibrational frequencies were used to investigate the nature of the adsorption interactions. Based on HOMO and LUMO distributions, the variation in the orbital distributions during the adsorption was studied. The non-covalent interaction isosurfaces and reduced density gradient scatter plots were also obtained to understand the interactions during adsorption. The post-adsorption orientations of the VOCs over GRA, BN and BCN were parallel to the plane of the nanosheets. The computations indicated increased van der Waals interactions between the VOCs and the adsorbent sheets. The analysis showed that the VOCs interact with the nanosheets through weak van der Waal forces and showed π-π stacking. The overall analysis showed that the order of adsorption of VOCs on the nanosheets was: GRA > BCN > BN.

Separation of Alcohols from n-Tetradecane Using 1-Ethyl-3-methylimidazolium Hydrogensulfate

Extraction of alcohols from n-tetradecane using various extraction solvents has been investigated at a range of temperatures from 295 to 393 K under ambient pressure. On the basis of the experimental liquid–liquid equilibrium data, the distribution ratio and selectivity were calculated for the extraction of 1-octanol, 1-decanol, and 1-dodecanol (C8–C12) in 1-ethyl-3-methylimidazolium hydrogensulfate [C2mim][HSO4] and sulfolane. Results showed that moderate selectivities were obtained in sulfolane with very low distribution coefficients. In contrast, [C2mim][HSO4] showed similar selectivity values with higher distribution coefficients. A study of a number of different 1-alcohols (C4–C12) showed that the decrease in hydrogen bonding compared to the increased van der Waals interactions between n-tetradecane and the higher-chain alcohols decreased the extraction selectivity in [C2mim][HSO4]. Increasing the temperature of the ionic liquid extraction medium resulted in increased chemical extraction for 1-butanol and 1-hexanol due to the formation of the corresponding alkylsulfate ionic liquid. In contrast, the selectivity decreased for 1-octanol, 1-decanol and 1-dodecanol due to the partial dissolution of the corresponding alkylsulfate ionic liquid into the n-tetradecane phase.

Mechanistic Insight into the Photo-Oxidation of Perfluorocarboxylic Acid over Boron Nitride.

Hexagonal boron nitride (hBN) can photocatalytically oxidize and degrade perfluorocarboxylic acids (PFCA), a common member of the per/polyfluoroalkyl substance (PFAS) family of water contaminants. However, the reaction mechanism governing PFCA activation on hBN is not yet understood. Here, we apply electronic grand canonical density functional theory (GC-DFT) to assess the thermodynamic and kinetic favorability of PFCA photo-oxidative activation on hBN: CnF2n+1COO- + h+ → CnF2n+1· + CO2. The oxidation of all PFCA chains is exothermic under illumination with a moderate barrier. However, the longer-chain PFCAs are degraded more effectively because they adsorb on the surface more strongly as a result of increased van der Waals interactions with the hBN surface. The ability of hBN to act as a photocatalyst is unexpected because of its wide band gap. Therefore, we apply both theoretical and experimental analyses to examine possible defects on hBN that could account for its activity. We find that a nitrogen-boron substitutional defect (NB), which generates a mid-gap state, can enhance UVC (ultraviolet C) absorption and PFCA oxidation. This work provides insight into the PFCA oxidation mechanism and reveals engineering strategies to design better photocatalysts for PFCA degradation.

Computational Insights into the Binding Mechanism of OxyS sRNA with Chaperone Protein Hfq.

Under the oxidative stress condition, the small RNA (sRNA) OxyS that acts as essential post-transcriptional regulators of gene expression is produced and plays a regulatory function with the assistance of the RNA chaperone Hfq protein. Interestingly, experimental studies found that the N48A mutation of Hfq protein could enhance the binding affinity with OxyS while resulting in the defection of gene regulation. However, how the Hfq protein interacts with sRNA OxyS and the origin of the stronger affinity of N48A mutation are both unclear. In this paper, molecular dynamics (MD) simulations were performed on the complex structure of Hfq and OxyS to explore their binding mechanism. The molecular mechanics generalized born surface area (MM/GBSA) and interaction entropy (IE) method were combined to calculate the binding free energy between Hfq and OxyS sRNA, and the computational result was correlated with the experimental result. Per-residue decomposition of the binding free energy revealed that the enhanced binding ability of the N48A mutation mainly came from the increased van der Waals interactions (vdW). This research explored the binding mechanism between Oxys and chaperone protein Hfq and revealed the origin of the strong binding affinity of N48A mutation. The results provided important insights into the mechanism of gene expression regulation affected by protein mutations.

Thermomechanical and Conductive Properties of Thiol–Ene Poly(ionic liquid) Networks Containing Backbone and Pendant Imidazolium Groups

A series of covalently cross-linked poly(ionic liquid) networks were prepared using thiol–ene “click” photopolymerization. In these networks, imidazolium groups are placed in the backbone and pendant to the main chain, creating a “hybrid”-type network architecture. The pendant imidazolium groups were incorporated into the networks from monofunctional “ene” monomers that contained either a terminal alkyl group at the imidazolium N-3 position of variable length (R = C1, C4, C8, C12, C16, or C20) or a variable alkyl tether spacer (n = 6 or 10) between the newly formed sulfide and the imidazolium ring. Thermal characterization of these networks indicated a general decrease in Tg as the length of the terminal alkyl chain length increased from C1 to C8, followed by an abrupt increase in Tg up to C20 due to increased van der Waals interactions between longer chains. X-ray scattering data confirmed the presence of chain-extended crystallites within the network cavities for the C16 and C20 systems, leading to the observed increase in Tg and the appearance of a melting transition for both systems. Ionic conductivities of the PIL networks were determined from dielectric relaxation spectroscopy (10–6 to 10–7 S/cm at 30 °C, 30% RH), and a direct correlation with polymer Tg was found.

Perspective: interesterified triglycerides, the recent increase in deaths from heart disease, and elevated blood viscosity.

The authors hypothesize that consumption of interesterified fats may be the cause of the continuous increase in cardiovascular deaths in the United States which began in 2011. Interesterification is a method of producing solid fats from vegetable oil and began to supplant partial hydrogenation for this purpose upon recognition of the danger of trans fats to cardiovascular health. Long, straight carbon chains, as are present in saturated and trans fatty acids, decrease the fluidity of the erythrocyte cell membrane, which decreases erythrocyte deformability and increases blood viscosity. This decrease in cell membrane fluidity is caused by increased van der Waals interactions, which also solidify dietary fats. Elevated blood viscosity is favored as the pathogenic mechanism by which trans fats increase cardiovascular mortality because changes in lipoprotein levels do not account for all the mortality attributable to their consumption. The rapid changes in cardiovascular mortality noted with the introduction and withdrawal of trans fats from the food supply are reviewed. The evidence implicating elevated blood viscosity in cardiovascular disease is also reviewed. Data regarding the production and consumption of interesterified fats in the US should be released in order to determine if there is an association with the observed increase in cardiovascular deaths.

Effect of Structure on Transport Properties (Viscosity, Ionic Conductivity, and Self-Diffusion Coefficient) of Aprotic Heterocyclic Anion (AHA) Room Temperature Ionic Liquids. 2. Variation of Alkyl Chain Length in the Phosphonium Cation.

A series of room-temperature ionic liquids (ILs) composed of triethyl(alkyl)phosphonium cations paired with three different aprotic heterocyclic anions (AHAs) (alkyl = butyl ([P2224](+)) and octyl ([P2228](+))) were prepared to investigate the effect of cationic alkyl chain length on transport properties. The transport properties and density of these ILs were measured from 283.15 to 343.15 K at ambient pressure. The dependence of the transport properties (viscosity, ionic conductivity, diffusivity, and molar conductivity) on temperature can be described by the Vogel-Fulcher-Tamman (VFT) equation. The ratio of the molar conductivity obtained from the molar concentration and ionic conductivity measurements to that calculated from self-diffusion coefficients (measured by pulsed gradient spin-echo nuclear magnetic resonance spectroscopy) using the Nernst-Einstein equation was used to quantify the ionicity of these ILs. The molar conductivity ratio decreases with increasing number of carbon atoms in the alkyl chain, indicating that the reduced Coulombic interactions resulting from lower density are more than balanced by the increased van der Waals interactions between the alkyl chains. The results of this study may provide insight into the design of ILs with enhanced dynamics that may be suitable as electrolytes in lithium ion batteries and other electrochemical applications.

Design of free‐standing microstructured conducting polymer films for enhanced particle removal from non‐uniform surfaces

ABSTRACTEfficient removal of particles from topologically‐complex surfaces is of significant import for a range of applications (e.g., explosive residue removal in security arenas). Here, we synthesize next‐generation polymeric particle removal swabs with tuned structural features to elucidate the influence of the polymer microstructure on the removal of trace particles from surfaces. Specifically, microstructured free‐standing films of the conducting polymer polypyrrole (PPy) were synthesized through template‐assisted electropolymerization techniques. The removal of polystyrene microspheres from representative aluminum surfaces of varying roughness was evaluated as a function of the PPy microstructure. PPy‐based microstructured swabs displayed increased particle trapping properties relative to non‐textured PPy‐based swabs and current commercial swabs. This increased effectiveness occurred from the more intimate particle‐swab contact, leading to increased van der Waals interactions for the microstructured swabs. Therefore, this effort provides critical design rules for the production of microstructured conducting polymer materials for their application toward advanced particle removal technologies. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 1968–1974

Langmuir monolayers composed of single and double tail sulfobetaine lipids

HypothesisOwing to structural similarities between sulfobetaine lipids and phospholipids it should be possible to form stable Langmuir monolayers from long tail sulfobetaines. By modification of the density of lipid tail group (number of carbon chains) it should also be possible to modulate the two-dimensional phase behaviour of these lipids and thereby compare with that of equivalent phospholipids. Potentially this could enable the use of such lipids for the wide array of applications that currently use phospholipids. The benefit of using sulfobetaine lipids is that they can be synthesised by a one-step reaction from cheap and readily available starting materials and will degrade via different pathways than natural lipids. The molecular architecture of the lipid can be easily modified allowing the design of lipids for specific purposes. In addition the reversal of the charge within the sulfobetaine head group relative to the charge orientation in phospholipids may modify behaviour and thereby allow for novel uses of these surfactants. ExperimentsStable Langmuir monolayers were formed composed of single and double tailed sulfobetaine lipids. Surface pressure-area isotherm, Brewster Angle Microscopy and X-ray and neutron reflectometry measurements were conducted to measure the two-dimensional phase behaviour and out-of-plane structure of the monolayers as a function of molecular area. FindingsSulfobetaine lipids are able to form stable Langmuir monolayers with two dimensional phase behaviour analogous to that seen for the well-studied phospholipids. Changing the number of carbon tail groups on the lipid from one to two promotes the existence of a liquid condensed phase due to increased Van der Waals interactions between the tail groups. Thus the structure of the monolayers appears to be defined by the relative sizes of the head and tail groups in a predictable way. However, the presence of sub-phase ions has little effect on the monolayer structure, behaviour that is surprisingly different to that seen for phospholipids.

Combined Experimental and Computational Study of the Gelation of Cyclohexane-Based Bis(acyl-semicarbazides) and the Multi-Stimuli-Responsive Properties of Their Gels.

The current study reports the one-step synthesis and gelation properties of cyclohexane-based bis(acyl-semicarbazide) gelators with an additional -NH group incorporated into urea moieties and carrying hydrophobic chains of varying length (C8-C18). The gels exhibited thermoreversibility and could be tuned in the presence of anions at different concentrations in addition their the ultrasound-responsive nature, thus making them multi-stimuli-responsive. The combined experimental and computational study on these gels reveals that the balance between two noncovalent interactions, viz., hydrogen bonding between the amide groups in acyl-semicarbazide moieties and van der Waals forces between long hydrocarbon tails, is found to be the determining factor in the process of organogelation. A systematic increase in alkyl chain length leads to equilibrium between these two types of noncovalent forces that is manifested in the spectral and thermal properties of the gels. The H-bonding interactions dominated up to a certain chain length, and further increases in the alkyl chain length led to increased van der Waals interactions as observed by IR, XRD, and thermal studies. Computational calculations were carried out on dimer structures of C8-C18 to understand the variation in noncovalent forces responsible for aggregate formation in the gel state as a function of the alkyl chain length. The results indicate that both intermolecular and intramolecular hydrogen bonding stabilize the aggregate structures. Supramolecular aggregation in the gel state led to the viscoelastic nature of the gels, and the addition of anions led to the disruption of self-assembly, which was studied by rheology.

Controlled release of 5-fluorouracil from microporous zeolites

Zeolite particles with different pore diameter and particle size were loaded with the model anticancer drug 5-fluorouracil. The loaded zeolites were characterized by means of SEM, XRD, DSC, XPS, N2 physisorption and FT-IR. Higher loading of 5-FU was observed for NaX-FAU than BEA. Release studies were carried out in HCl 0.1N. Release of 5-FU from NaX-FAU showed exponential-type behaviour with the drug fully released within 10min. In the case of BEA, the kinetics of 5-FU shows a multi-step profile with prolonged release over time. Molecular dynamics simulations showed that diffusion of the drug molecule through the BEA framework is lower than for NaX-FAU due to increased van der Waals interaction between the drug and the framework. The effect of zeolitic particles on the viability of Caco-2 monolayers showed that the NaX-FAU particles cause a reduction of cell viability in a more pronounced way compared with the BEA particles. From the Clinical EditorThis article describes zeolite-based nanoparticles in generating time-controlled release of 5-FU from zeolite preparations for anti-cancer therapy.

Synthesis, Characterization, and Computational Studies of Cycloparaphenylene Dimers

Two novel arene-bridged cycloparaphenylene dimers (1 and 2) were prepared using a functionalized precursor, bromo-substituted macrocycle 7. The preferred conformations of these dimeric structures were evaluated computationally in the solid state, as well as in the gas and solution phases. In the solid state, the trans configuration of 1 is preferred by 34 kcal/mol due to the denser crystal packing structure that is achieved. In contrast, in the gas phase and in solution, the cis conformation is favored by 7 kcal/mol (dimer 1) and 10 kcal/mol (dimer 2), with a cis to trans activation barrier of 20 kcal/mol. The stabilization seen in the cis conformations is attributed to the increased van der Waals interactions between the two cycloparaphenylene rings. These calculations indicate that the cis conformation is accessible in solution, which is promising for future efforts toward the synthesis of short carbon nanotubes (CNTs) via cycloparaphenylene monomers. In addition, the optoelectronic properties of these dimeric cycloparaphenylenes were characterized both experimentally and computationally for the first time.

Characterization of English ivy (Hedera helix) adhesion force and imaging using atomic force microscopy

English ivy (Hedera helix) is well known for its ability to climb onto and strongly adhere to a variety of solid substrates. It has been discovered that the ivy aerial rootlet secretes an adhesive composed of polysaccharide and spherical nanoparticles. This study aims to characterize the mechanical properties of the nanocomposite adhesive using atomic force microscopy (AFM). The adhesive was first imaged by AFM to visualize the nanocomposite. Mechanical properties were then determined at various time points, from secretion to hardening. The experimental results indicate that the ivy adhesive exhibited strong adhesion strength and high elasticity. There was a decrease in adhesive force over time, from 298 to 202 nN during the 24-h study. Accompanying with it were the limited changes in extension length and Young’s modulus. The limited curing process of the ivy adhesive helps fill gaps in the attaching surface, leading to more intimate contact and increased van der Waals interactions with the surface. However, study based on a mechanical model indicated that van der Waals force alone is not significant enough to account for all of the measured force. Other chemical interactions and cross linking likely contribute to the strong adhesion strength of ivy.

Terahertz Spectra and Normal Mode Analysis of the Crystalline VA Class Dipeptide Nanotubes

Terahertz (THz) vibrational modes are characterized by nonlocal, collective molecular motions which are relevant to conformational changes and molecular functions in biological systems. We have investigated the THz spectra of a set of small bionanotubes which can serve as very simple models of membrane pores, and have examined the character of the THz modes which can impact transport processes. In this work, THz spectra of the crystalline VA class dipeptide nanotubes were calculated at both the harmonic and vibrational self-consistent field (VSCF) level using the CHARMM22 force field with periodic boundary conditions. Comparison of the calculated THz spectra against the experimental spectra revealed that the VSCF corrections generally improved the predictions in the low-frequency region. The improvements were especially manifested in the overall blue-shifts of the VSCF frequencies relative to the harmonic values, and blue shifts were attributed to the overall positive coupling strengths in all systems. Closer examination of the motions in the most significantly coupled normal mode pairs leads us to propose that, when two similar side-chain squeezing modes are coupled, the rapidly increased van der Waals interactions can lead to a stiffening of the effective potential, which in turn leads to the observed blue-shifts. However, we also noted that when the side-chain atoms become unphysically proximate and the van der Waals repulsion becomes too large, the VSCF calculations tend to deviate in the high frequency region and for the system of l-isoleucyl-l-valine. In addition, normal-mode analysis revealed a series of channel-breathing motions in all systems except l-valyl-l-alanine. We show that the inner products of the backbone vibrations between these channel-breathing motions divided the remaining VA class dipeptide systems into two subgroups. It is suggested that these modes may facilitate a pathway for the guest molecule absorption, substitution and removal in the VA class dipeptide nanotubes. Normal mode analysis also demonstrated that the THz motions may contribute to the pore permeability either directly by changing the pore size, or indirectly by affecting the solvent-host effective potentials.

Synthesis of Dehydrobenzo[18]annulene Derivatives and Formation of Self-Assembled Monolayers: Implications of Core Size on Alkyl Chain Interdigitation

The synthesis of a series of dodecadehydrotribenzo[18]annulene ([18]DBA) derivatives is reported, together with their steady-state absorption and fluorescence properties. The main focus, though, is on the self-assembly of these compounds at the liquid-solid interface as investigated with scanning tunneling microscopy (STM), highlighting the effect of alkyl chain orientation and alkyl chain length on the molecular ordering. Owing to the large triangular pi-electron system of the [18]DBAs, two different types of alkyl chain orientation are observed. The observed changes in the monolayer networks upon elongation of the alkyl chains are attributed to the increased van der Waals interactions between molecules and substrate. The effect of the core size on the alkyl chain orientation and, as a result, the monolayer structure is discussed in relation to the results obtained previously for triangularly-shaped dehydrobenzo [12]annulene ([12]DBA) derivatives and triphenylene derivatives. A guideline for substituent spacing allowing control of molecular alignment for large planar pi-electron systems utilizing directional alkyl chain interdigitation is also discussed.

Failure Mechanisms of Capacitive MEMS RF Switch Contacts

Microelectromechanical systems (MEMS) radio frequency (RF) switches hold great promise in a myriad of commercial, aerospace, and military applications. In particular, capacitive type switches with metal-to-dielectric contacts (typically Au- on-silicon nitride) are suitable for high frequency (≥10 GHz) applications. However, there is little fundamental understanding of the factors determining the performance and reliability of these devices. To address this void in understanding, we conducted fundamental studies of Au-on-Si3N4 contacts at various bias voltages using a micro/nanoadhesion apparatus as a switch simulator. The experiments were conducted in air at 45% relative humidity. The switch simulator allows us to measure fundamental parameters such as contact force and adhesion, which cannot be directly measured with actual MEMS switches. Adhesion was found to be the primary failure mechanism. Both a mechanical and electrical effect contributed to high adhesion. The mechanical effect is adhesion growth with cycling due to surface smoothening, which allows increased van der Waals interaction. The electrical effect on adhesion is due to electrostatic force associated with excess charge trapped in the dielectric, and was only observed at 40 V bias and above. The two effects are additive, but the electrical effect was not present until surfaces were worn smooth by cycling. Surface smoothening increases the electric field in the dielectric, which leads to trapped charge and higher adhesion. Excessive adhesion can explain decreased lifetime at high bias voltage previously reported with actual capacitive MEMS switches. Aging of open contacts in air was found to reduce adhesion. Surface analysis data show the presence and growth (in air) of an adventitious film containing carbon and oxygen. The adventitious film is responsible for aging related adhesion reduction by increasing surface separation and/or reducing surface energy. No junction growth and force relaxation with time were observed in capacitive switch contacts, as was previously observed with Au–Au contacts at low current in direct current MEMS switches.

Molecular mechanisms of adefovir sensitivity and resistance in HBV polymerase mutants: a molecular dynamics study

Molecular modeling studies of adefovir diphosphate with the wild type and the mutant HBV polymerase–DNA complex demonstrated that the increase in adefovir sensitivity toward HBV polymerase mutants (rtL180M, rtM204V/I, rtL180M-M204V/I) is a result of increased van der Waals interaction and is supplemented by the decreased affinity of natural substrate toward the mutant HBV polymerase. In the case of rtN236T mutant, loss of two hydrogen bonds accompanied by significant decrease in electrostatic interactions is observed, which explains the observed decrease in drug sensitivity and binding affinity of adefovir diphosphate toward the rtN236T mutant HBV polymerase.