| 1. |
- Coroaba, Adina, et al.
(författare)
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Probing the supramolecular features via π–π interaction of a di-iminopyrene-di-benzo-18-crown-6-ether compound : experimental and theoretical study
- 2020
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Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 10:63, s. 38304-38315
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Tidskriftsartikel (refereegranskat)abstract
- A novel DPyDB-CN-18C6 compound was synthesised by linking a pyrene moiety to each phenyl group of dibenzo-18-crown-6-ether, the crown ether, through –HCN– bonds and characterized by FTIR, 1H-NMR, 13C-NMR, TGA, and DSC techniques. The quantitative 13C-NMR analysis revealed the presence of two position isomers. The electronic structure of the DPyDB-CN-18C6 molecule was characterized by UV-vis and fluorescence spectroscopies in four solvents with different polarities to observe particular behavior of isomers, as well as to demonstrate a possible non-bonding chemical association (such as ground- and excited-state associations, namely, to probe if there were forming dimers/excimers). The interpretation of the electronic structure was realized through QM calculations. The TD-CAM-B3LYP functional, at the 6-311+G(d,p) basis set, indicated the presence of predominant π → π* and mixed π → π* + n → π* transitions, in line with the UV-vis experimental data. Even though DPyDB-CN-18C6 computational studies revealed a π-extended conjugation effect with predominantly π → π* transitions, thorough fluorescence analysis was observed a weak emission, as an effect of PET and ACQ. In particular, the WAXD analysis of powder and thin films obtained from n-hexane, 1,2-dichloroethane, and ethanol indicated an amorphous organization, whereas from toluene a smectic ordering was obtained. These results were correlated with MD simulation, and it was observed that the molecular geometry of DPyDB-CN-18C6 molecule played a defining role in the pyrene stacking arrangement.
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| 2. |
- de Villiers Engelbrecht, Leon, et al.
(författare)
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Molecular Perspective on Solutions and Liquid Mixtures from Modelling and Experiment
- 2022
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Ingår i: Soft Matter Systems for Biomedical Applications. - Cham : Springer Nature. - 9783030809232 - 9783030809249 ; , s. 53-84
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Konferensbidrag (refereegranskat)abstract
- Liquid solutions and mixtures are part of our everyday lives and also important for their chemical and industrial applications. While considered fairly unattractive substances when kept in bottles and containers, their behavior as molecules can be completely the opposite, continuously attracting scientists to explain it better. Very strong repulsive and attractive interactions between the molecules can create most intriguing local structures, aggregates and complexes, whose spatial organization is often difficult to rationalize. Also, the same mixture can behave completely differently depending on the composition ratio, affecting strongly its macroscopic properties. To gain insight into the complex world of binary liquid mixtures, deep eutectic solvents and ionic liquid systems, combined theoretical and experimental studies are necessary. In this chapter we introduce the methodology of computer simulations and illustrate with several examples of the often-unexpected behavior of many liquid mixtures.
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| 3. |
- de Villiers Engelbrecht, Leon, et al.
(författare)
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Theoretical and Experimental Study of the Excess Thermodynamic Properties of Highly Nonideal Liquid Mixtures of Butanol Isomers plus DBE
- 2021
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 125:2, s. 587-600
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Tidskriftsartikel (refereegranskat)abstract
- Binary alcohol + ether liquid mixtures are of significant importance as potential biofuels or additives for internal combustion engines and attract considerable fundamental interest as model systems containing one strongly H-bonded self-associating component (alcohol) and one that is unable to do so (ether), but that can interact strongly as a H-bond acceptor. In this context, the excess thermodynamic properties of these mixtures, specifically the excess molar enthalpies and volumes (H-E and V-E), have been extensively measured. Butanol isomer + di-n-butyl ether (DBE) mixtures received significant attention because of interesting differences in their V-E, changing from negative (1- and isobutanol) to positive (2- and tert-butanol) with increasing alkyl group branching. With the aim of shedding light on the differences in alcohol self-association and cross-species H-bonding, considered responsible for the observed differences, we studied representative 1- and 2-butanol + DBE mixtures by molecular dynamics simulations and experimental excess property measurements. The simulations reveal marked differences in the self-association of the two isomers and, while supporting the existing interpretations of the H-E and V-E in a general sense, our results suggest, for the first time, that subtle changes in H-bonded topologies may contribute significantly to the anomalous volumetric properties of these mixtures.
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| 4. |
- Mocci, Francesca, et al.
(författare)
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DNA-Polyamine Interactions : Insight from Molecular Dynamics Simulations on the Sequence-Specific Binding of Spermidine3
- 2022
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Ingår i: Soft Matter Systems for Biomedical Applications. - Cham : Springer Nature. - 9783030809232 - 9783030809249 ; , s. 163-192
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Konferensbidrag (refereegranskat)abstract
- DNA is a polyanion stabilized in vivo by positively charged counterions, including metal ions and small organic molecules, e.g., putrescine2+, spermidine3+, and spermine4+. In this chapter, after a brief review of previous studies on such DNA-counterion interactions, we focus the attention on the interactions between spermidine3+ and DNA. In this context, we present our original molecular dynamics simulation study to establish the specificity of the binding of polyamines to different nucleotide sequence motifs. Spermidine3+ molecules tend to be localized in the minor groove of the DNA double helix around the regions with AATT and ATAT nucleotide sequences. In the major groove, the polyamine does not bind to the AT-rich sequences, but instead localizes on the CG-region. The positioning of polyamines on the DNA surface also determines the DNA-DNA contacts due to the formation of polyamine cross-links. The cross-linking spermidine3+ molecules are localized parallel to the sugar-phosphate backbone of the double helix, neutralizing the negatively charged phosphate groups. The presented results are important for understanding the role of spermidine3+ in the biological functions of DNA and also have implications for possible technological applications.
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| 5. |
- Neamtu, Andrei, et al.
(författare)
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Molecular dynamics simulations reveal the hidden EF-hand of EF-SAM as a possible key thermal sensor for STIM1 activation by temperature
- 2023
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 299:8
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Tidskriftsartikel (refereegranskat)abstract
- Intracellular calcium signaling is essential for many cellular processes, including store-operated Ca2+ entry (SOCE), which is initiated by stromal interaction molecule 1 (STIM1) detecting endoplasmic reticulum (ER) Ca2+ depletion. STIM1 is also activated by temperature independent of ER Ca2+ depletion. Here we provide evidence, from advanced molecular dynamics simulations, that EF-SAM may act as a true temperature sensor for STIM1, with the prompt and extended unfolding of the hidden EF-hand subdomain (hEF) even at slightly elevated temperatures, exposing a highly conserved hydrophobic Phe108. Our study also suggests an interplay between Ca2+ and temperature sensing, as both, the canonical EF-hand subdomain (cEF) and the hidden EF-hand subdomain (hEF), exhibit much higher thermal stability in the Ca2+-loaded form compared to the Ca2+-free form. The SAM domain, surprisingly, displays high thermal stability compared to the EF-hands and may act as a stabilizer for the latter. We propose a modular architecture for the EF-hand-SAM domain of STIM1 composed of a thermal sensor (hEF), a Ca2+ sensor (cEF), and a stabilizing domain (SAM). Our findings provide important insights into the mechanism of temperature-dependent regulation of STIM1, which has broad implications for understanding the role of temperature in cellular physiology.
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| 6. |
- Perepelytsya, Sergiy, et al.
(författare)
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Conformational flexibility of spermidine3+ interacting with DNA double helix
- 2023
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Ingår i: Journal of Molecular Liquids. - : Elsevier. - 0167-7322 .- 1873-3166. ; 389
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Tidskriftsartikel (refereegranskat)abstract
- Natural polyamines play a key role in many biological processes, particularly in the stabilization of DNA double helix structure in the cell nucleus. Among others, the conformational flexibility of polyamines, such as spermidine, is an essential property for the formation of complexes with DNA. Yet, the characterization of the conformational space of polyamines has not been fully elucidated. Using atomistic molecular dynamics (MD) simulations, we present a detailed study of the conformational space of spermidine3+ both in solution and in interaction with DNA. We have identified more than 2000 distinct conformations, which can be grouped into seven modes. Notably, the relative population of these modes is highly affected by the interaction of spermidine3+ with DNA, thus representing a fingerprint of complex formation. In particular, three of the seven dihedral angles of spermidine3+ are predominantly in trans conformation (with or without DNA), while the other four dihedral angles are observed to switch between trans, gauche+ and gauche-. The preference between the latter conformational states was analyzed in terms of the distinct energy contributions composing the potential energy. Overall, our results shed some light on the conformational equilibrium and dynamics of spermidine3+, which in turn is important for understanding the nature of its interaction with DNA.
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| 7. |
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| 8. |
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| 9. |
- Vasiliu, Tudor, et al.
(författare)
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Caging Polycations: Effect of Increasing Confinement on the Modes of Interaction of Spermidine3+ With DNA Double Helices
- 2022
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Ingår i: Frontiers in Chemistry. - : Frontiers Media S.A.. - 2296-2646. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Polyamines have important roles in the modulation of the cellular function and are ubiquitous in cells. The polyamines putrescine2+, spermidine3+, and spermine4+ represent the most abundant organic counterions of the negatively charged DNA in the cellular nucleus. These polyamines are known to stabilize the DNA structure and, depending on their concentration and additional salt composition, to induce DNA aggregation, which is often referred to as condensation. However, the modes of interactions of these elongated polycations with DNA and how they promote condensation are still not clear. In the present work, atomistic molecular dynamics (MD) computer simulations of two DNA fragments surrounded by spermidine3+ (Spd3+) cations were performed to study the structuring of Spd3+ “caged” between DNA molecules. Microsecond time scale simulations, in which the parallel DNA fragments were constrained at three different separations, but allowed to rotate axially and move naturally, provided information on the conformations and relative orientations of surrounding Spm3+ cations as a function of DNA-DNA separation. Novel geometric criteria allowed for the classification of DNA-Spd3+ interaction modes, with special attention given to Spd3+ conformational changes in the space between the two DNA molecules (caged Spd3+). This work shows how changes in the accessible space, or confinement, around DNA affect DNA-Spd3+ interactions, information fundamental to understanding the interactions between DNA and its counterions in environments where DNA is compacted, e.g. in the cellular nucleus.
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| 10. |
- Vasiliu, Tudor, et al.
(författare)
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In silico study of PEI-PEG-squalene-dsDNA polyplex formation: the delicate role of the PEG length in the binding of PEI to DNA
- 2021
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Ingår i: Biomaterials Science. - : Royal Society of Chemistry. - 2047-4830 .- 2047-4849. ; 9:19, s. 6623-6640
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Tidskriftsartikel (refereegranskat)abstract
- Biocompatible hydrophilic polyethylene glycol (PEG) is widely used in biomedical applications, such as drug or gene delivery, tissue engineering or as an antifouling component in biomedical devices. Experimental studies have shown that the size of PEG can weaken polycation-polyanion interactions, like those between branched polyethyleneimine (b-PEI) and DNA in gene carriers, but details of its cause and underlying interactions on the atomic scale are still not clear. To better understand the interaction mechanisms in the formation of polyplexes between b-PEI-PEG based carriers and DNA, we have used a combination of in silico tools and experiments on three multicomponent systems differing in PEG MW. Using the PEI-PEG-squalene-dsDNA systems of the same size, both in the all-atom MD simulations and in experimental in-gel electrophoresis measurements, we found that the binding between DNA and the vectors is highly influenced by the size of PEG, with the binding efficiency increasing with a shorter PEG length. The mechanism of how PEG interferes with the binding between PEI and DNA is explained using a two-step MD simulation protocol that showed that the DNA-vector interactions are influenced by the PEG length due to the hydrogen bond formation between PEI and PEG. Although computationally demanding we find it important to study molecular systems of the same size both in silico and in a laboratory and to simulate the behaviour of the carrier prior to the addition of bioactive molecules to understand the molecular mechanisms involved in the formation of the polyplex.
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