Search

The work presents correlations between the physicochemical properties of the carrier and the active substance and optimization of the conditions for creating an active system based on PAMAM dendrimers and doxorubicin. The study monitored the influence of the ionized form of the doxorubicin molecule on the efficiency of complex formation. The deprotonated form of doxorubicin occurs under basic conditions in the pH range of 9.0-10.0. In the presence of doxorubicin, changes in the zeta potential of the complex concerning the initial system are observed. These changes result from electrostatic interactions between the drug molecules and external functional groups. Based on changes in the absorbance intensity of UV-vis spectra, the binding of the drug in the polymer structure is observed depending on the pH of the environment and the molar ratio. Optimal conditions for forming complexes occur under alkaline conditions. UV-vis, Fourier transform infrared spectroscopy, and circular dichroism spectroscopy confirmed the stability of the formed dendrimer-DOX complex. Molecular dynamics simulations were conducted to gain a deeper insight into the molecular mechanism of DOX adsorption on and within the G4.0 PAMAM dendrimers. It was observed that the protonation state of both the dendrimer and DOX significantly influences the adsorption stability. The system exhibited high stability at high pH values (∼9-10), with DOX molecules strongly adsorbed on the dendrimer surface and partially within its bulk. However, under lower pH conditions, a reduction in adsorption strength was observed, leading to the detachment of DOX clusters from the dendrimer structure.

Poly(amidoamine) dendrimer (PAMAM)/carbon quantum dot (CQD) nanohybrids are promising candidates for many biomedical applications, including drug delivery. Effectively designing a hybrid nanocarrier requires a deep understanding of the interactions of the hybrid nanoparticle with the drug to ensure drug stability and therapeutic efficiency. In this study, we utilized fully atomistic molecular dynamics (MD) simulations to investigate the adsorption behavior of a doxorubicin (DOX) anticancer drug onto a zwitterion/PAMAM/CQD hybrid nanocarrier. The hybrid nanoparticles were composed of CQD, at two oxidation levels, grafted with PAMAM dendrimers of generation 3 (G3) or 4 (G4) decorated with zwitterion monomers. Our work reveals that the generation of the grafted dendrimer was the primary determinant of efficient adsorption of DOX, unlike the oxidation level of CQD or dendrimer surface chemistry. After grafting, the G4 dendrimers assume a more stretched conformation compared to the G3 dendrimers. This allowed DOX molecules to penetrate inside the dendritic cavities of G4 dendrimers, resulting in enhanced drug protection. The hydrophobic interaction, between the aromatic structure of DOX molecules and the nonpolar parts of dendrimers, has been proven to play a crucial role in mediating the adsorption of drug molecules. These findings provide valuable insights to assist in the design of a zwitterion/PAMAM/CQD hybrid nanoplatform for drug delivery applications.

The work deals with molecular dynamics (MD) simulations of protonated, human telomeric i-motif deoxyribonucleic acid (DNA) with functionalized graphene. We studied three different graphene sheets: unmodified graphene with hydrogen atoms attached to their edges and two functionalized ones. The functionalization of graphene edge consists in attaching partially protonated or dissociated amine and carboxyl groups. We found that in all cases the protonated i-motif adsorbs strongly on the graphene surface. The biased MD simulations showed that the work necessary to drag the i-motif out from amine-doped graphene is about twice larger than that in other cases. In general, the system i-motif/amine-doped graphene stands out from the rest, e.g., in this case, the i-motif adsorbs its side with 3' and 5' ends oriented in the opposite to surface direction. In other cases, the DNA fragment is adsorbed to graphene by 3' and 5' ends. In all cases, the adsorption on graphene influences the i-motif internal structure by changing the distances between i-motif strands as well as stretching or shortening the DNA chain, but only in the case of amine-doped graphene the adsorption affects internal H-bonds formed between nucleotides inside the i-motif structure.

In this work, we studied, using computational methods, the protonation reactions of telomeric DNA fragments being due to interaction with carboxylated carbon nanotubes. The applied computational methodology is divided into two stages. (i) Using classical molecular dynamics, we generated states in which carboxyl groups are brought to the vicinity of nitrogen atoms within the cytosine rings belonging to the DNA duplex. (ii) From these states, we selected two systems for systematic quantum chemical studies aimed at the analysis of proton-transfer reactions between the carboxyl groups and nitrogen atoms within the cytosine rings. Results of molecular dynamics calculations led to the conclusion that sidewall-functionalized carbon nanotubes deliver carboxyl groups slightly more effectively than the on-tip-functionalized ones. The latter can provide carboxyl groups in various arrangements and more diverse quality of approach of carboxyl groups to the cytosines; however, the differences between various arrangements of carboxyl groups are still not big. It was generally observed that narrow nanotubes can access the cytosine pocket easier than wider ones. Quantum chemical calculations led however to the conclusion that a direct proton transfer from the carboxyl group to the nitrogen atom within the cytosine ring is impossible under normal conditions. Precisely, we detected either very high activation barrier for the proton-transfer reaction or instability of the reaction product, i.e., its spontaneous decomposition toward reaction substrates.

This work deals with molecular dynamics simulations of human telomeric i-motif DNA interacting with functionalized single-walled carbon nanotubes. We study two kinds of i-motifs differing by the protonation state of cytosines, i.e., unprotonated ones representative to neutral pH and with half of the cytosines protonated and representative to acidic conditions. These i-motifs interact with two kinds of carbon nanotubes differing mainly in chirality (diameter), i.e., (10, 0) and (20, 0). Additionally, these nanotubes were on-tip functionalized by amino groups or by guanine- containing residues. We found that protonated i-motif adsorbs strongly, although not specifically, on the nanotube surfaces with its 3' and 5' ends directed toward the surface and that adsorption does not affect the i-motif shape and hydrogen bonds existing between C:C + pairs. The functional groups on the nanotube tips have minimal effect either on position of i-motif or on its binding strength. Unprotonated i-motif, in turn, deteriorates significantly during interaction with the nanotubes and its binding strength is rather high as well. We found that (10, 0) nanotubes destroy the i-motif shape faster than (20, 0). Moreover the i-motif either tries to wrap the nanotube or migrates to its tip and becomes immobilized due to interaction with guanine residue localized on the nanotube tip and attempts to incorporate its 3' end into the nanotube interior. No hydrogen bonds exist within the unprotonated i-motif prior to and after adsorption on the nanotube. Thus, carbon nanotubes do not improve the stability of unprotonated i-motif due to simple adsorption or just physical interactions. We hypothesize that the stabilizing effect of carbon nanotubes reported in the literature is due to proton transfer from the functional group in the nanotube to cytosines and subsequent formation of C:C + pairs.

Molecular dynamics simulations were employed to study the properties of G-quadruplex and i-motif secondary DNA structures formed within the canonical telomere fragment of the Watson-Crick duplex. These secondary structures were built symmetrically in the same place of the duplex and were subjected to the analysis in standard unbiased simulations and using metadynamics scheme for the determination of potential of mean force associated with the enforced unfolding of the i-motif parts of the systems. Also, enforced formation of i-motif structures, starting from partially unfolded duplex, were studied in order to find whether formation of i-motif facilitates spontaneous formation of G-quadruplex. We found that i-motif formed from single stranded DNA is unstable at neutral pH and room temperature. On the other hand, the i-motif is strongly stabilized by the presence of complementary G-quadruplex, which should be the most likely configuration when these secondary structures form from double stranded DNA. The stabilization is observed either in neutral or in acidic pH though in the neutral case the i-motif can also reveal considerable stability in the hairpin configuration. We did not observe spontaneous folding of the guanine-rich strand into the G-quadruplex when the cytosine rich strand was dragged to i-motif configuration. This observation suggests that both folding and unfolding transitions are kinetically blocked.

This work deals with an analysis of drugs carriers based on the structure of a carbon nanotube using large-scale atomistic molecular dynamics simulations. The analyzed systems link several functions in a single architecture. They are as follows: (i) the sidewalls and tips of carbon nanotubes are covalently functionalized by polyethylene glycol-folic acid conjugates, and this approach allows for creation of hydrophytic and biocompatible systems; (ii) doxorubicin is kept in the internal space of a carbon nanotube as a mixture with dyes (p-phenylenediamine or neutral red)-it allows for pH-controlled release or alteration of the interaction topology; (iii) the mixture of doxorubicin and dyes in the nanotube interior is additionally sealed by fullerene nanoparticles which act as pistons at acidic pH and loosen the tangle of polyethylene glycol chains at the nanotube tips. This enhances the release of doxorubicin from the nanotube when compared to the analogous system but without the fullerene caps; (iv) another function of the carrier can be activated by filling of the fullerenes by magnetic material-then, the carrier can be visualized by means of magnetic resonance imaging, it can realize magnetic hyperthermia of tumor cells, and intense rotation of the nanoparticles can be induced by the application of an external magnetic field. That rotation enhances the release of doxorubicin from the nanotube and leads to the increase of the rotational temperature. The studies show that the proposed design of the drug-doxorubicin carrier reveals very promising properties. Its fabrication is absolutely feasible, as all individual stages necessary for its construction have been confirmed in the literature.

This work shows results of a theoretical survey, based on molecular dynamics simulation, of potential applicability of doxorubicin coadsorption with various dyes molecules on/in carbon nanotubes as a drug delivery system. The central idea is to take advantage of the dyes charge distribution change upon switching the pH of the environment from neutral (physiological 7.4) to acidic one (∼5.5 which is typical for tumor tissues). This work discusses results obtained for four dye molecules revealing more or less interesting behavior. These were bromothymol blue, methyl red, neutral red, and p-phenylenediamine. All of them reveal pKa in the range 5-7 and thus will undergo protonation in that pH range. We considered coadsorption on external walls of carbon nanotubes and sequential filling of the nanotubes inner hollow space by drug and dyes. The latter approach, with the application of neutral red and p-phenylenediamine as blockers of doxorubicin, led to the most promising results. Closer analysis of these systems allowed us to state that neutral red can be particularly useful as a long-term blocker of doxorubicin encapsulated in the inner cavity of (30,0) carbon nanotube at neutral pH. At acidic pH we observed a spontaneous release of neutral red from the nanotube and unblocking of doxorubicin. We also confirmed, by analysis of free energy profiles, that unblocked doxorubicin can spontaneously leave the nanotube interior at the considered conditions. Thus, that system can realize pH controlled doxorubicin release in acidic environment of tumor tissues.

Adsorptive separation of chiral molecules is a powerful technique that has long been used in the chemical and pharmaceutical industries. An important challenge in this field is to design and optimize new adsorbents to provide selective discrimination of enantiomers. In this article, we introduce an off-lattice model of chiral adsorption on nanostructured surfaces and slit pores with the aim of predicting their enantioslective properties. The concept presented here involves finding the optimal chiral pattern of active sites on the pore walls that maximizes the difference between the binding energies of the enantiomers. Our initial effort focuses on chiral molecules that do not have specific interactions with the pore surface. One candidate meeting this requirement is 1,2-dimethylcyclopropane (DMCP), a chiral hydrocarbon whose interaction with a model pore surface was described using the Lennard-Jones potential. To model the adsorption of DMCP, we used the Monte Carlo simulation method. It was demonstrated that the separation of the enantiomers of DMCP is hardly obtainable because of the smoothness of the potential energy surface for molecules physisorbed in the pore. However, the simulated results allowed the identification of key factors that influence the binding of the enantiomers of DMCP to the pore walls with a special distribution of active sites. This information will be useful in future considerations of the adsorption of more complex chiral molecules.

The adsorption energy distribution usually refers to localized monolayers of adsorbate at thermodynamic equilibrium. Many papers have been published that analyze its influence on adsorption isotherms, heats of adsorption, and adsorption kinetics. However, the adsorption energy distribution, in its classical thermodynamic equilibrium sense, may be not as useful as expected. This is because many important processes involving adsorption have dynamic character and reactant particles have a finite time for penetration of the adsorbent. The above suggests that some adsorption centers located in less accessible fragments of the surface can be invisible in a dynamic process. However, under conditions allowing the thermodynamic equilibrium such adsorption centers could noticeably contribute to the adsorption energy distribution. The aim of this work is to measure the adsorption energy distributions of special rough surfaces using a dynamic method. This method is based on the molecular dynamics simulation of an ideal gas flowing over a sample surface. The ideal gas particles penetrate the surface, and at the moment of collision of a gas particle with the surface the Lennard-Jones potential energy is calculated. This energy can be identified with the adsorption energy at a given point on the surface. The surfaces used in the calculations have been created using two surface growth models (i.e., random deposition and ballistic deposition). The application of these highly disordered surfaces enables us to draw some general conclusions about the properties of real surfaces that are usually far from any deterministic geometry.

This article deals with a quantitative analysis of thermodesorption spectra of ammonia: a technique commonly applied to study the surface acidity of solids. The method used for determination of adsorption energy distributions of ammonia is the same as that published recently for the case of hydrogen thermodesorption (Panczyk, T.; et al. Langmuir 2005, 21, 7311). The developed theoretical expression describing the thermodesorption process is based on the statistical rate theory (SRT) and its analysis leads to the conclusion that majority of thermodesorption processes, carried out under flow conditions, are in fact quasi-equilibrium ones. Similar conclusion has already been drawn by some authors applying the classical absolute rate theory (ART) for analysis of thermodesorption data. This conclusion has important practical consequences. Namely, it greatly simplifies the quantitative analysis of thermodesorption processes since there is no need to use any kinetic approaches to that purpose. The quantitative analysis of thermodesorption spectra can thus be based on commonly accepted relations following from equilibrium thermodynamics. It is worth noting that in quasiequilibrium conditions either the SRT or the ART lead to this same expression with only a slightly different meaning of some constants. Thus, in quasiequilibrium conditions there is no need to decide which theoretical approach should be applied. As an illustration, the ammonia thermodesorption spectra from the modified nickel catalysts are analyzed. The catalysts were prepared by the coprecipitation method and differ by the amount of MgO and NiO, whereas the amount of Al(2)O(3) is constant and equals 30%. It was stated that the presence of MgO reduces the number of acid centers corresponding to high values of ammonia adsorption energy.

Two generalizations of the statistical rate theory (SRT) approach have been developed for the kinetics of adsorption/desorption on/from heterogeneous surfaces and then compared to each other. The first of them is an improved version of the description based on the condensation approximation (CA) used by us. The other one is an exact generalization for the Langmuir model of adsorption. The latter generalization does not lead to simple analytical expressions for the rate of adsorption/desorption as the CA approach does for typical adsorption energy distributions. The comparison of these two approaches suggests, however, that at small and very high surface coverages the CA approach may not be sufficiently accurate. Very intriguing results are obtained when the developed SRT kinetic equations are applied to describe the kinetics of sorption in carbon molecular sieves. It appears that the fit of experimental data is then equally good as that obtained by assuming that the rate of sorption is controlled by surface diffusion in pores. Also, it is shown that the square-root dependence on time of adsorption at small initial coverages cannot be treated as a definite proof for that sorption proceeds via surface diffusion, as is commonly assumed.

The thermodesorption spectra of hydrogen from coprecipitated catalysts (70-x)NiO-xMgO-30Al(2)O(3) (x = 0-50%(wt)) are reported. The catalysts were calcined at 400 degrees C and reduced with H(2) at 20-800 degrees C and for 3 h at 800 degrees C. NiO reduction degree was between 49.3 and 92.1%. The active surface areas changed from 8.4 to 32.4 m(2)/g whereas mean size of nickel crystallites was between 3.7 and 9.7 nm. The TPD spectra were next analyzed in order to determine the adsorption energy distributions functions. To obtain these functions a theoretical model of adsorption/desorption kinetics based on the statistical rate theory (SRT) was applied. This approach allows for determination of the adsorption energy at nonequilibrium conditions as well as at quasiequilibrium conditions. The resulting distribution functions reveal the presence of two main bands of adsorption energy. Some correlation is found between the determined distributions of adsorption energy and the size of nickel crystallites determined using the XRD method. The presence of MgO favors creation of high energy adsorption sites on Ni crystallites.

We propose a model of the dissociative adsorption of hydrogen on nickel single-crystal face. In this model, we treat the Ni(100) surface as a strongly correlated energetically heterogeneous surface, because the density functional theory (DFT) studies indicate that hydrogen atoms may adsorb either on hollow sites (energetically more favorable, binding energy 48 kJ/mol H) or bridge sites with the binding energy less by 11 kJ/mol H. The essential assumption of the proposed model is that the dissociation of the hydrogen molecule is possible only over the topmost Ni atom, and the resulting H atoms may adsorb either on two free hollow sites (but the adjacent bridge sites must be free) or two bridge sites (the adjacent hollow sites must be free). If the above condition is not fulfilled, then the dissociation and adsorption are impossible. The second assumption is that the rate (probability) of the associative desorption is limited by the rate of diffusion of H atoms on the surface. This is because the two H atoms desorb, giving an H2 molecule, only when they meet on two adjacent hollow-bridge sites. Our model recovers very well the behavior of the experimental equilibrium adsorption isotherms as well as kinetic isotherms. As a result, we stated that hydrogen atoms are not completely free on the surface, but they cannot also be considered localized at room and elevated temperatures. Additionally, while analyzing the kinetic adsorption isotherms, we stated that the rate-limiting step during the dissociative adsorption of H2 is the disintegration of the activated complex and the subsequent adsorption of hydrogen atoms.