Benzophosphol-3-yl Triflates as Precursors of 1,3-Diarylbenzophosphole Oxides.

A simple method for the synthesis of 3-arylbenzophosphole oxides under Suzuki-Miyaura coupling conditions has been presented. It employs benzophosphol-3-yl triflate starting materials which, prior to our work, had not been used for the synthesis of 3-arylbenzophosphole oxides. The reactions proceed over 24 h and provide a library of 3-arylbenzophosphole oxides. The synthetic access to the benzophosphol-3-yl triflates has been improved. The preliminary photophysical properties of some 3-arylbenzophosphole oxides have been investigated by absorption and emission measurements. The theoretical calculations were performed to establish structure-property relationships.

Interaction of Chondroitin and Hyaluronan Glycosaminoglycans with Surfaces of Carboxylated Carbon Nanotubes Studied Using Molecular Dynamics Simulations.

Interaction of ß-D-glucopyranuronic acid (GlcA), N-acetyl-ß-D-glucosamine (GlcNAc), N-acetyl-ß-D-galactosamine (GalNAc) and two natural decameric glycosaminoglycans, hyaluronic acid (HA) and Chondroitin (Ch) with carboxylated carbon nanotubes, were studied using molecular dynamics simulations in a condensed phase. The force field used for carbohydrates was the GLYCAM-06j version, while functionalized carbon nanotubes (fCNT) were described using version two of the general amber force field. We found a series of significant differences in carbohydrate-fCNT adsorption strength depending on the monosaccharide molecule and protonation state of surface carboxyl groups. GlcNAc and GalNAc reveal a strong adsorption on fCNT with deprotonated carboxyl groups, and a slightly weaker adsorption on the fCNT with protonated carboxyl groups. On the contrary, GlcA weakly adsorbs on fCNT. The change in protonation state of surface carboxyl groups leads to the reversal orientation of GlcNAc and GalNAc in reference to the fCNT surface, while GlcA is not sensitive to that factor. Adsorption of decameric oligomers on the surface of fCNT weakens with the increasing number of monosaccharide units. Chondroitin adsorbs weaker than hyaluronic acid and incorporation of four Ch molecules leads to partial detachment of them from the fCNT surface. The glycan-fCNT interactions are strong enough to alter the conformation of carbohydrate backbone; the corresponding conformational changes act toward a more intensive contact of glycan with the fCNT surface. Structural and energetic features of the adsorption process suggest the CH-π interaction-driven mechanism.

From Cyclo[18]carbon to the Novel Nanostructures-Theoretical Predictions.

In this paper, we present a number of novel pure-carbon structures generated from cyclo[18]carbon. Due to the very high reactivity of cyclo[18]carbon, it is possible to link these molecules together to form bigger molecular systems. In our studies, we generated new structures containing 18, 36 and 72 carbon atoms. They are of different shapes including ribbons, sheets and tubes. All these new structures were obtained in virtual reactions driven by external forces. For every reaction, the energy requirement was evaluated exactly when the corresponding transition state was found or it was estimated through our new approach. A small HOMO-LUMO gap in these nanostructures indicates easy excitations and the multiple bonds network indicates their high reactivity. Both of these factors suggest that some potential applications of the new nanostructures are as components of therapeutically active carbon quantum dots, terminal fragments of graphene or carbon nanotubes obtained after fracture or growing in situ in catalytic reactions leading to the formation of carbonaceous materials.

The carbohydrate glycosylphosphatidylinositol anchor chain under mechanical stress.

Carbohydrates have quite complicated micro heterogenic structure which may undergo different structural transitions. Due to their extreme flexibility it is very difficult to investigate such structural changes experimentally. In these studies we want to predict what structural and conformational changes are possible in the carbohydrate glycosylphosphatidylinositol anchor chain (GPI): the tetrasaccharide with the unique sequence Man-α(1 → 2)-Man-α(1 → 6)-Man-α(1 → 4)-GlcN-α. This is a very important biomolecule associated with the processes of transmitting various types of signals in the cells of living organisms. In order to investigate conformational and structural changes in GPI we use in these studies the theoretical Enforced Geometry Optimization (EGO) method. In this method a molecule is exposed to a mechanical stress caused by external forces applied to selected atoms. It turned out that under external stretching forces the mannopyranose unit can change its 4C1 chair conformation into three different forms: 1S3, oS2 and B2,5. The initial 4C1 glucosamine ring can transit into the twisted boat 1S3 and the boat Bo,3 conformations. The obtained results confirm the high flexibility of the GPI anchor sugar chain.

Search for transition states with external forces.

It is much more difficult to find on the potential energy surface (PES) a transition state (TS) than a local minimum (LM). We propose a new methodology which makes this task much easier. Applying external forces to nuclei in a molecule we can locate on PES not just one particular TS but a number of consecutive transition states. With our approach it is possible to move over PES from one transition state to another without involving any local minima. The latter can be located in a separate step through the reaction path calculations performed for every transition state found before. Preliminary results for the 2-fluorofuran molecule illustrate the usefulness of the proposed method.

Efficient sampling of high-energy states by machine learning force fields.

Regarding their application in the field of molecular sciences, machine learning (ML) methods are capable of combining the high accuracy of ab initio potentials with an efficiency closer to that of classical molecular mechanics. By relying on the reference data (e.g., atomic configurations and corresponding energies), the ML algorithms can reconstruct the potential energy surface for simple molecular systems, which may subsequently serve as a computationally inexpensive force field. The accuracy of such an ML force field is highly dependent on the character of the dataset that was used for its training. In this work, we show that omitting the high-energy states, which results from following the Boltzmann distribution, may lead to a catastrophic loss of accuracy in certain regions of the configurational phase space. To overcome this challenge, we have proposed an alternative solution for generating the ML input data. The most essential step is the biased subsampling of the configurations, aimed at increasing the population of hardly accessible states, usually located on energy barriers. The applicability of the proposed procedure is demonstrated on the example of conformational rearrangements in the two flexible, heterocyclic molecules. This approach provides an essential component required to obtain the ML force fields, accurate within the whole configurational phase space of the system.

Simulation of the conformational flexibility of the mycodextran under external forces.

Mycodextran-also known as nigeran-is an unbranched polysaccharide made of α-d-glucopyranose units alternatively connected by (1 → 3) and (1 → 4) glycosidic linkages produced intracellularly by Aspergillus niger and Penicillium crustosum. In this work we examine possible enforced conformational transitions in the glucopyranose rings in the nigeran oligosaccharide chains. In order to simulate such structural changes we used the Enforced Geometry Optimization (EGO) method.

Isomerization and Decomposition of 2-Methylfuran with External Forces.

The primary goal of this project was to evaluate the performance of the Standard and Enforced Geometry Optimization (SEGO) method which we have recently developed. The SEGO method has been designed for an automatic location of multiple minima on the molecular Potential Energy Surface (PES), and its usefulness has been demonstrated so far for three molecules only. In this project we applied the SEGO method to explore the 2-methylfuran (2MF) PES. Our choice was not accidental: this molecule recently gained a great deal of interest as a potential candidate for biofuel, and therefore its pyrolysis is extensively studied. To understand pyrolysis of 2MF a detailed knowledge about its PES is needed. In these studies we explored the 2MF PES and located a surprisingly large number of local minima corresponding to 2MF isomers and decomposition products. Some of the 2MF isomers and fragments have amazing structures which most likely were previously unknown. All structures presented in this paper were found in an automatic manner as a result of the enforced chemical reactions driven by the SEGO method. Thus, in these studies we have not only proven that the SEGO method is a very efficient tool for exploring molecular potential energy surfaces, but we also obtained very detailed knowledge about the 2MF PES.

Theoretical studies of the pyranose ring under mechanical stress.

In this work we use our Enforced Geometry Optimization (EGO) method to investigate conformational transitions in the pyranose ring under mechanical stress caused by external forces. We examine possible transitions and/or inversions induced by external forces in the pyranose ring in the chair conformation with two axial glycosidic bonds. The results obtained provide new insight into the mechanism of the conformational transitions which strongly depends on substituents present in a pyranose ring. We also conclude that interpretation of AFM force-extension curves is not necessarily straightforward; not every plateau there corresponds to a conformational transition and not every transition can be clearly seen as a plateau.

Simulation of force spectroscopy experiments on galacturonic acid oligomers.

Pectins, forming a matrix for cellulose and hemicellulose, determine the mechanics of plant cell walls. They undergo salient structural changes during their development. In the presence of divalent cations, usually calcium, pectins can form gel-like structures. Because of their importance they have been the subject of many force spectroscopy experiments, which have examined the conformational changes and molecular tensions due to external forces. The most abundant unit present in the pectin backbone is polygalacturonic acid. Unfortunately, experimental force spectroscopy on polygalacturonic acid molecules is still not a trivial task. The mechanism of the single-molecule response to external forces can be inferred by theoretical methods. Therefore, in this work we simulated such force spectroscopy experiments using the Enforced Geometry Optimization (EGO) method. We examined the oligomeric (up to hexamer) structures of α-D-galacturonic acid exposed to external stretching forces. The EGO simulation of the force spectroscopy appropriately reproduced the experimental course of the enforced conformational transition: chair →inverted chair via the twisted boat conformation(s) in the pyranose ring of α-D-galacturonic acid. Additionally, our theoretical approach also allowed to determine the minimum oligomer size adequate for the description of nano-mechanical properties of (poly)-α-D-galacturonic acid.

Instability of 2,2-di(pyridin-2-yl)acetic acid. Tautomerization versus decarboxylation.

The DFT calculations at the B3LYP level with 6-311G** basis set were carried out in order to reveal whether tautomerization or decarboxylation is responsible for the instability of 2,2-di(pyridin-2-yl)acetic (DPA) and 1,8-diazafluorene-9-carboxylic (DAF) acids. The carboxyl protons in both compounds are involved in the intramolecular hydrogen bonds (the pyridine nitrogen atoms are the hydrogen bond acceptors). Although formation of two intramolecular OH · · · N hydrogen bonds in the enols of both carboxylic acids enables effective electron delocalization within the quasi rings (· · · HO - C = C - C = N), only ene-1,1-diol of DAF has somewhat lower energy than DAF itself (ΔE is ca. 7 kcal mol(-1)). DPA and its enediol have comparable energies. Migration of the methine proton toward the carbonyl oxygen atom (to form enediols) requires overstepping the energy barriers of 55-57 kcal mol(-1) for both DPA and DAF. The enaminone tautomers of the acids, formed by migration of this proton toward the pyridine nitrogen atom, are thermodynamically somewhat more stable than the respective enediols. The energy barriers of these processes are equal to ca. 44 and 62 kcal mol(-1) for DPA and DAF, respectively. Thus, such tautomerization of the acids is not likely to proceed. On the other hand, the distinct energetic effects (ca. 15 kcal mol(-1)) favor decarboxylation. This process involves formation of (E)-2-(pyridin-2(1H)-ylidenemethyl)pyridine and its cyclic analogue followed by their tautomerization to (dipyridin-2-yl)methane and 1,8-diazafluorene, respectively. Although the later compound was found to be somewhat thermodynamically more stable, kinetic control of tautomerization of the former is more distinct.