Theoretical Problems of Adsorption

 

MAIN RESEARCH TOPICS

Research interests of our group are focused on the meaning and influence of adsorption phenomena on properties of systems revealing significant importance in applied science and/or biomedical applications. We also focus on model systems which analysis helps to understand the influence of microscopic factors on the observed macroscopic properties. 

Current research topics:

  • One of the most current research topics is the analysis of the telomeric DNA fragments by means of molecular dynamics. Telomeres are terminal parts of chromosomes build of highly repetitive sequences of nucelotides (TTAGGG):(CCCTAA). Telomeres protect the ends of the chromosome from deterioration or from fusion with neighboring chromosome. They also control the number of cell division cycles. Within the telomeric DNA the guanine and cytosine rich strands can adopt noncanonical higher order spatial structures: G-quadruplex and i-motif. It has been shown that formation of these structures blocks the inifinite proliferative capacity of cells being the results of the overexpression of telomerase. The aim of our studies is thus the analysis of the processes of formation, deterioration and stability of the G-quadruplex and i-motif structures depending on various factors like pH or interaction with nanostructured objects. Particularly, we focus on the analysis of G-quadruplex and i-motif adsorption on the surfaces of carbon nanotubes. Analysis of these processes is crucial for the development of novel smart drug delivery systems.
  • Another research topic is the theoretical studies (methods: EGO, SEGO) of mechanical properties and structural changes occurring under the external forces for various molecular systems. The research attention is mainly focused on mechanofore molecules which can react to mechanical stimuli and change their color during the stretching / compression process. Such systems may have self-healing properties and may be used as mechanosensors. The aim of the research is to propose possible mechanisms of enforced structural changes in such systems.
  • Still another research tasks is the development of new, classical molecular mechanics force fields dedicated for studying the structure and conformation of carbohydrates. We developed a series of extensions of the GROMOS force field intended to use in the explicit-solvent molecular dynamics simulation of the following classes of compounds: (i) carbohydrates containing ionized, protonated or esterified carboxylic groups (uronates, in particular: pectins and alginates); (ii) carbohydrates containing furanose rings (furanose monomers, e.g. ribose and arabinose; dimers, e.g. sucrose and oligomers, so-called fructans). In addition to the development, testing and validation of newly-designed force fields, molecular dynamics simulations carried out by using the final parameters offer an insight into a number of phenomena occurring at the molecular level with the participation of the compounds of interest.
  • The other research topic relies on the application of the quantum-chemistry methods in order to elucidate selected aspects regarding: (i) stereoelectronic effects in furanose molecules; (ii) the anomeric, tautomeric and conformational equilibria in mono-, di- and oligosaccharide molecules that contain both pyranose and furanose units.

 

MAIN ACHIEVEMENTS

  • An isolated i-motif consists of at least 22 nitrogenous bases forming the sequence (CCCTAA)3CCCT. Its existence is possible due to formation of Hoogsteen pairs, contrary to the canonical form of DNA which is stabilized due to formation of the complementary Watson-Crick pairs. I-motif reveals a high thermodynamic stability at acidic conditions when the Hoogsteen CC+ pairs can form between the protonated and native forms of cytosines. Our calculations show that at physiological conditions of pH, when deprotonation of C+ occurs, the i-motif undergoes spontaneous deterioration towards the disordered hairpin or random coil structures. 

Fig.1 Deterioration of the i-motif structure towards the random coil as a result of the deprotonation of cytosines at the neutral pH

  • A different situation takes place when the i-motif appears within the duplex and within the complementary guanine rich strand already exists or forms the G-quadruplex. Our calculations lead to the conclusion that even at the neutral pH and upon a total deprotonation of cytosines the i-motif does not undergo a spontanoues decomposition. There appear only some weakening of the spatial structure and cleveage of hydrogen bonds within the Hoogsteen pairs. However, the overall spatial structure of the i-motif is preserved and deterioration towards the hairpin or random coil needs overcoming significant energetic barriers of the order of 70 kJ/mol.

 

Fig. 2. Potential of mean force determined for the enforced deterioration of the i-motif at the neutral pH. The presence of the complementary G-quadruplex stabilizes the i-motif also at the physiological pH.

  • According to ScienceAlert the i-motif has been recently (2018) observed in a living cell which means that it can exist at physiological conditions as well. Previous studies of the i-motif were always limited to the reduced pH and to in vitro analysis. Our calculation results indicate that the appearance of the i-motif at physiological conditions can be associated with the stabilizing effect of the G-quadruplex located in the vicinity of the i-motif. We currently work on the interaction of the G-quadruplex and i-motif with the functionalized carbon nanotubes. The aim of this study is to explain the observed stabilizing effect of single-walled carbon nanotubes on the structure of the i-motif, as reported in the literature.
  • Activation of the mechanophore molecule (often located inside the polymer network) occurs by breaking the covalent bonds. This causes fluorescent emissions that can signal impending material damage. For this reason, such systems (polymers enriched with mechanophore molecules) can act as the specific sensors and the potential self-healing/self-reinforcing materials. Due to their various potential applications mechanophores are currently intensively investigated. The majority of mechano-responsive polymeric systems have been based on the spiropyran molecule. This colorless mechanophore can undergo a 6-π electrocyclic ring-opening reaction accompanied by a color change to yield planar merocyanine thorough C-O bond cleavage (see Fig. 3)

Fig 3. The enforced conversion: spiropyran →merocyanine.

 

  • The mechanism of the photoinduced spiropyran⇆merocyanine conversion was investigated by the experimental and theoretical methods. However, the mechanochemical picture of the such conversion pathway induced by the external force is still far from complete. We proposed possible enforced reaction mechanism obtained within the Enforced Geometry Optimization (EGO) approach. The enforced geometry optimization pathway: energy changes vs. optimization cycles for the selected stretching force (f = 0.070 a.u) is displayed in Fig. 4.

Fig. 4 The geometry optimization history for the selected stretching force 0.070 a.u.

 

  • Although it cannot be treated as a formal reaction path, it may provide some remarkable information about such a force-driven process and can be useful for localization of some stationary points (transition states and minima) on the potential energy surface (PES). During the enforced elongation process the molecular energy increases reaching a maximum (cycle 42) and then decreases (a minimum at the 60th cycle). This can be matched to passing through the transition state. It can be corroborated by the relaxation process (optimization without any external forces) for the lowest energy structure (cycle: 60) and by the transition state searching procedure with the highest (maximum) energy structure (cycles: 42) taken as the initial guess. The re-optimization (without forces) of the structures related to the cycle 60 leads to the stable (verified by vibrational analysis) minimum. For maximum energy structure related to the cycle 42 a transition state (verified also by vibrational analysis) was found.
  • Development of the molecular mechanics force fields for simulation of carbohydrates containing either furanose or pyranose units and allowing for simulations of saccharides of any chain length (from the monomer level), with an arbitrary type of glycosidic bonds between monomers, varying anomery, chemical heterogeneity of the chain, possible functionalization of selected functional groups (O-alkylation, ionization or esterification of carboxylic groups) and possibility of branching. The developed force fields belong to the GROMOS family; they are compatible with the SPC water model and already existing parameter sets (from version 53A6 upwards, including the 56A6CARBO set for pyranoses).
  • Creation of a quantitative description of the effect of pH on conformational degrees of freedom in uronate molecules. The pH value affects the rotation of the exocyclic carboxylic substituent; depending on the considered compound, it also may affect the ring-inversion properties. The same variable slightly affects the conformation of the glycosidic linkage and does not affect the conformation of the lactol group.

  •  Structural models of complexes created by pectin and alginate chains with calcium ions have been developed. It was shown that the dynamic conformations of complexes differing by the orientation of sugar chains (parallel vs. antiparallel) show a number of significant differences that can be interpreted in the context of calcium-induced aggregation occurring on a larger scale.
  • Systematic influence of the polar solvent on the conformation of the furanose ring has been proved to exist. This influence is manifested by generation of the energy barriers with a height of 3-7 kJ/mol, located at the OE and EO ring conformers. This effect is independent of the presence or absence of the ring substituent(s) and contributes to the wide applicability of the so-called two-state model, routinely used when analyzing the NMR data related to furanosides.

 

Finished research topics:

  • Adsorption of magnetic nanoparticles on carbon nanotubes together with an analysis of their magnetically triggered desorption/detachment. Such processes are of great importance in designing of smart drug delivery systems being able to change their internal structure in response to some external triggering factor (eg. magnetic field). Thus, they are able to release encapsulated drugs in a given place and time. Therefore, a detailed analysis is devoted to interaction of typical therapeutic agents with carbon nanotubes as well as with various ligands which modify adsorptive properties of carbon nanotubes. Effects due to magnetic anisotropy and magnetization reversal within the nanoparticles body frames are also of great importance.
  • Theoretical study focused on the dynamics and thermodynamics of the conformational changes (1C4 chair ↔ 4C1 chair) in molecules of the selected carbohydrates consisting of the six-membered pyranose rings.The ring conformation of the hexopyranose-based carbohydrate molecules is one of the central issues in glycobiology. The ring conformers (puckers) can determine the biological function and activity of carbohydrate and the dynamic equilibrium between puckers determines the macroscopic hydrodynamic properties of the carbohydrate polymers. Due to the extremely high free energy barriers separating particular ring conformers, most of the theoretical studies is focused on the detailed description of the free energy landscapes, neglecting the dynamic features of the conformational changes. Our study, based on the transition path sampling simulations is aimed at filling this gap.
  • The mutarotation of carbohydrates is one of the fundamental chemical reactions, important in the context various fields of science. Although being the classical 'textbook' reaction, some of its details still remain unknown. We plan to initiate the detailed computational investigation by using the molecular dynamics method, according to the QM/MM (quantum mechanics/molecular mechanics) protocol which means that part of the system (e.g. glucose molecule and selected, catalytic, water molecules) are modeled with the accuracy of quantum mechanics while the remaining part with that of classical biomolecular force fields (e.g. the TIP3P model of water)
  • Enforced structural changes in molecules. Theoretical studies are focused on various types of structural changes (e.g., conformational transitions, cis-trans isomerism, intramolecular rearrangements, etc.) caused by the external forces in the molecules of biological importance.
  • Adsorption of globular proteins on the biocompatible surface using a broad range of analytical techniques including quartz crystal microbalance with dissipation of energy (QCM-D) and surface plasmon resonance (SPR-MP). QCM-D and MP-SPR are powerful methods that enable highly sensitive, qualitative, real-time, label-free, and noninvasive detection of adsorbed proteins. Combinations of the above techniques have provided significant information on the mechanisms behind protein-material interactions, structural changes and biomolecular rearrangements. Work will be performed bidirectional, experimentally and theoretically with the use of molecular dynamics (MD). This project gives new perspectives for the development of novel protein/enzyme immobilization strategies for biomedical or biosensor applications.
  • Theoretical description of adsorption of simple ions and of surfactants at oxide/electrolyte interfaces (Special attention focused on enthalpies of adsorption and on effects of surface heterogeneity)
  • Equilibria and kinetics of gas adsorption on energetically heterogeneous solid surfaces, (also thermodesorption), adsorption in zeolites, and mixed-gas adsorption.

 

 Main achievements in finished research topics:

  • Design and computational study of the magnetically triggered molecular nanocontainer which is able to release of drug molecules (eg. cisplatin) in response to external magnetic field. Monte Carlo and Molecular Dynamics simulations allowed us to determine critical ranges of parameters which the nanocontiner must satisfy in order to work in the requested manner. The main factor responsible for the function of the nanocontineris its total energy profile accompanying the cycles of capping/uncapping. That energy is a function of dispersion forces between magnetic nanoparticle and carbon nanotube shell material which cover the magnetic core and magnetic properties of the core itself and sizes of both nanoparticle and carbon nanotube.The ground state of the nanocontainer is the capped state. The uncapping occurs as a result of the interaction with the external magnetic field, however, the magnetic nanoparticles must reveal high values of magnetic anisotropy constant. The release of drug (cisplatin) proceeds according to the activated one dimensional diffusion mechanism. It was found that that mechanism consists of two stages. A simple analytical formula which allows for prediction of long time limits of the release process was also derived.
  • In the investigation of the hexopyranose ring puckering we focused on the α-d- and β-d-glucopyranose molecules (GlcA and GlcB, respectively), treated as model systems. The results allowed for: identifying the distinct local minima of the free energy corresponding to the states intermediate for the 4C11C4 transitions; assigning the time-characteristics to this transition and intermediate states; performing the search for the optimal reaction coordinate based on the Peters-Trout approach (likelihood maximization). Additionally, the structures corresponding to the 4C11C4 transition states (TS) have been found; surprisingly, in the case of GlcA, the water dynamics has very little influence on the probability of the TS evolution either to 4C1 or to 1C4. The different result obtained for GlcB (large influence of water dynamics on the behavior of TS as well as the poor applicability of the Peters-Trout approach for calculation of the reaction coordinate) speaks for slightly different mechanisms of the 4C11C4 puckering in molecules of GlcB and GlcA, probably with the larger contribution of transitions over diffusive energy barriers, characteristic for rough free energy landscapes in the case of GlcA. The obtained results contribute to understanding the mechanisms governing the conformational changes in the carbohydrate rings. Additionally, the developed algorithms may be used to study other conformational changes in the related systems.
  • The atomic force microscopy (AFM) is a relevant tool to explore the mechanical/conformational stability of the biomolecules at single molecule level. The proper interpretation of experimental AFM force-extension curves is still difficult. Molecular insights on the origins of mechanical responses can be inferred from simulations and theoretical methods, e.g. the EGO model (Enforced Geometry Optimization).

    Experimental works dedicated to conformation changes in individual α -D-galacturonic acid molecules imposed by external forces showed that the transformation 4C11C4 takes place through the twisted boat conformation. The EGO simulation of the AFM experiment for α-D-galacturonic acid properly reproduces this experimental trend. The EGO model predicts essentially the same mechanism as the molecular dynamics and constrained geometry optimization calculations. The EGO method predicts three possible permanent conformational changes in the considered α-D-galacturonic acid oligomers (up to hexamer). The type of conformational transitions generally depends on the unit position in the oligosaccharide chain.

  • Structure and properties of protein layers: from biomolecules to a functional layer (a combined experimental and simulation study). We performed analysis of conformational changes of lysozyme (LSZ) at various interfaces by Quartz Crystal Microbalance (QCM-D) and Surface Plasmon Resonance (MP-SPR). Furthermore, QCM-D can be used to study the adsorption behavior (kinetics, adsorbed amount and the thickness of protein film layer). Effect of solution concentration, pH and electrolyte type was studied to elucidate the nature of the association processes. We have found that the protein adsorption strongly depends on ionic strength and pH. MD simulation suggested that LSZ adsorbs strongly at surface through Arg and Lys residues from the N,C-terminal face. Moreover, the dominant interactions driving adsorption are the electrostatic interaction between LSZ and solid surface. Adsorbed LSZ can diffuse on the surface and create aggregates and clusters with other LSZ molecules.

Fig. 5. Lysozyme adsorption efficiencies on mica surface. The project realized with cooperation with Department of Chemical and Process Engineering, University of Strathclyde, Glasgow United Kingdom

  • Reversible swelling process of 6th generation poly (amidoamine) ( PAMAM) dendrimers. Our results supply the first reliable experimental evidence that swelling of G6 generation PAMAM dendrimer is reversible. Furthermore, we showed that this process is essentially modulated by condensation of the counterions at the dendrimer surface. These findings give a valuable insight into the dendrimer science and challenge for the further theoretical and experimental study, in particular, for assessing a degree of penetration of water and the counterions into dendrimer molecules, under the various conditions of pH, the ionic strength and the electrolyte type. This results have also a practical merit, because, they indicate that dendrimers may be used as stimulus-responsive drug delivery carriers, which can release a trapped drug upon a conformational transition induced in the dendrimer molecule by change in pH or the ionic strength.

Fig. 6. Reversible swelling process of 6th generation poly (amidoamine) ( PAMAM) dendrimers

  • quantitative description of the enthalpic effects accompanying adsorption of simple ions at oxide/electrolyte interfaces. It includes all kinds of experiments carried out so far, i.e. batch experiments, calorimetric titration and flow calorimetry. Also studies of temperature dependence of ion adsorption were presented. This theoretical description was first developed for some model, well-defined surfaces of oxides, and next generalized by considering the energetic heterogeneity of the actual oxide/electrolyte interfaces. For the first time, it was shown, that drawing mathematical consequences of the existence of the Common Intersection Point makes it possible to establish interrelations of certain important physicochemical parameters.
  • application of the Scaled Particle Theory to quantitatively describe the adsorption of surfactants at both solid/liquid and gas/liquid interfaces. That new theoretical description is at present the only one which has made possible a simultaneous quantitative description of both adsorption isotherms and of the accompanying enthalpic effects. It has been demonstrated that in the case of large surface aggregates the lateral interactions between these aggregates do not play a significant role in surfactant adsorption.
  • theoretical description of the kinetics of gas adsorption on energetically heterogeneous solid surfaces. That new description was based on the Statistical Rate Theory of Interfacial Transport