Deciphering the mechanism of γ-cyclodextrin's hydrophobic cavity hydration: an integrated experimental and theoretical study.

Cyclodextrins (CDs) are host systems with inherent capability for inclusion complex formation with various molecular entities, mostly hydrophobic substances. Host CDs are highly accommodative to water molecules as well and usually contain water in the native state. There is still an ongoing discussion on both the total number of water molecules and their preferred binding position inside the cavities of the CDs.

Density Functional Theory Prediction of Laser Dyes-Cucurbit[7]uril Binding Affinities.

Among a variety of diverse host molecules distinguished by specific characteristics, the cucurbit[n]uril (CB) family stands out, being widely known for the attractive properties of its representatives along with their increasingly expanding area of applications. The presented herewith density functional theory (DFT)-based study is inspired by some recent studies exploring CBs as a key component in multifunctional hydrogels with applications in materials science, thus considering CB-assisted supramolecular polymeric hydrogels (CB-SPHs), a new class of 3D cross-linked polymer materials. The research systematically investigates the inclusion process between the most applied representative of the cavitand family CB[7] and a series of laser dye molecules as guests, as well as the possible encapsulation of a model side chain from the photoanisotropic polymer PAZO and its sodium-containing salt.

Naphthalimide-Based Amphiphiles: Synthesis and DFT Studies of the Aggregation and Interaction of a Simplified Model System with Water Molecules.

Systems containing amphiphilic/pathic molecules have the tremendous capacity to self-assemble under appropriate conditions to form morphologies with well-defined structural order (systematic arrangement), nanometer-scale dimensions, and unique properties. In this work, the synthesis of novel naphthalimide-based amphiphilic probes that have 1,8-naphthalimide as the fluorescence signal reporting group, octyl as hydrophobic head, and PEG as hydrophilic tail, is described. These designed molecules represent a new class of self-assembling structures with some promising features.

Implementation of Three Gallium-Based Complexes in the "Trojan Horse" Antibacterial Strategy against : A DFT Approach.

Microorganisms of the ESKAPE group pose an enormous threat to human well-being, thus requiring a multidisciplinary approach for discovering novel drugs that are not only effective but utilize an innovative mechanism of action in order to decrease fast developing resistance. A promising but still hardly explored implementation in the "Trojan horse" antibacterial strategy has been recognized in gallium, an iron mimicry species with no known function but exerting a bacteriostatic/bactericidal effect against some representatives of the group. The study herewith focuses on the bacterium and its siderophore acinetobactin in its two isomeric forms depending on the acidity of the medium.

-Methyl- and -Phenylpiperazine Functionalized Styryl Dyes Inside Cucurbiturils: Theoretical Assessment of the Factors Governing the Host-Guest Recognition.

The family of cucurbiturils (CBs), the unique pumpkin-shaped macrocycles, has received great attention over the past four decades owing to their remarkable recognition properties. They have found diverse applications including biosensing and drug delivery technologies. The cucurbituril complexation of guest molecules can modulate their pKs, improve their solubility in aqueous solution, and reduce the adverse effects of the drugs, as well as enhance the stability and/or enable targeted delivery of the drug molecule.

Electrostatic interactions - key determinants of the metal selectivity in La and Ca binding proteins.

Nearly half of all known proteins contain metal co-factors. In the course of evolution two dozen metal cations (mostly monovalent and divalent species) have been selected to participate in processes of vital importance for living organisms. Trivalent metal cations have also been selected, although to a lesser extent as compared with their mono- and divalent counterparts.

Cu/Ag Competition in Type I Copper Proteins (T1Cu).

Due to the similarity in the basic coordination behavior of their mono-charged cations, silver biochemistry is known to be linked to that of copper in biological systems. Still, Cu/ is an essential micronutrient in many organisms, while no known biological process requires silver. In human cells, copper regulation and trafficking is strictly controlled by complex systems including many cytosolic copper chaperones, whereas some bacteria exploit the so-called "blue copper" proteins.

Lanthanides as Calcium Mimetic Species in Calcium-Signaling/Buffering Proteins: The Effect of Lanthanide Type on the Ca/Ln Competition.

Lanthanides, the 14 4f-block elements plus Lanthanum, have been extensively used to study the structure and biochemical properties of metalloproteins. The characteristics of lanthanides within the lanthanide series are similar, but not identical. The present research offers a systematic investigation of the ability of the entire Ln series to substitute for Ca in biological systems.

Metal-Assisted Complexation of Fluorogenic Dyes by Cucurbit[7]uril and Cucurbit[8]uril: A DFT Evaluation of the Key Factors Governing the Host-Guest Recognition.

With the emergence of host-guest systems, a novel branch of complexation chemistry has found wide application in industries such as food, pharmacy, medicine, environmental protection and cosmetics. Along with the extensively studied cyclodextrins and calixarenes, the innovative cucurbiturils (CB) have enjoyed increased popularity among the scientific community as they possess even better qualities as cavitands as compared to the former molecules. Moreover, their complexation abilities could further be enhanced with the assistance of metal cations, which can interestingly exert a dual effect on the complexation process: either by competitively binding to the host entity or cooperatively associating with the CB@guest structures.

Host-guest complexation of cucurbit[7]uril and cucurbit[8]uril with the antimuscarinic drugs tropicamide and atropine.

Cucurbiturils are useful excipients in eye drop formulations: they can increase the water solubility of the drug, enhance drug absorption into the eye, improve aqueous stability and reduce local irritation. Effective and safe drug delivery is, however, a challenge and the information on the host (CBs)/guest (tropicamide and atropine) interactions can help improving the existing treatments and develop novel therapies not limited only to eye diseases/conditions. Since this carrier system can easily modify the properties of the drug and ensure its delivery at the targeted ocular tissue, further insight into the intimate mechanism of the host-guest recognition is crucial.

Competition between Ag and Ni in nickel enzymes: Implications for the Ag antibacterial activity.

Silver's antimicrobial properties have been known for centuries, but exactly how it kills bacteria is still a mystery. Information on the competition between the native Ni and abiogenic Ag cations in bacterial systems is also critically lacking. For example, urease, a famous nickel-containing enzyme that hydrolyzes urea into carbon dioxide and ammonia (a key step in the biogeochemical nitrogen cycle on Earth), is inhibited by Ag cations, but the molecular mechanism of silver's action is poorly understood.

Theoretical Insight into the Phosphate-Targeted Silver's Antibacterial Action: Differentiation between Gram (+) and Gram (-) Bacteria.

Although silver is one of the first metals finding broad applications in everyday life, specific key points of the intimate mechanism of its bacteriostatic/bactericidal activity lack explanation. It is widely accepted that the antimicrobial potential of the silver cation depends on the composition and thickness of the bacterial external envelope: the outer membrane in Gram-negative bacteria is more prone to Ag attack than the cell wall in Gram-positive bacteria. The major cellular components able to interact strongly with Ag (teichoic acids, phospholipids, and lipopolysaccharides) contain mono/diesterified phosphate moieties.

Mini-Review on Structure-Reactivity Relationship for Aromatic Molecules: Recent Advances.

Recent advances in quantifying nucleophilic reactivities in chemical reactions and intermolecular interactions of aromatic molecules are reviewed. This survey covers experimental (IR frequency shifts induced by hydrogen bonding) and theoretical (modeling of potential energy surfaces, atomic charges, molecular electrostatic potential) approaches in characterizing chemical reactivity. Recent advances in software developments assisting the evaluation of the reactive sites for electrophilic aromatic substitution are briefly discussed.

Complexation of trivalent metal cations (Al, Ga, In, La, Lu) to cucurbiturils: a DFT/SMD evaluation of the key factors governing the host-guest recognition.

Cucurbiturils (CBs), the pumpkin-shaped macrocycles, are suitable hosts for an array of neutral and cationic species. A plethora of host-guest complexes between CBs and a variety of guest molecules has been studied. However, much remains unknown, even in the complexation of very simple guests such as metal cations.

Strontium Binding to α-Parvalbumin, a Canonical Calcium-Binding Protein of the "EF-Hand" Family.

Strontium salts are used for treatment of osteoporosis and bone cancer, but their impact on calcium-mediated physiological processes remains obscure. To explore Sr interference with Ca binding to proteins of the EF-hand family, we studied Sr/Ca interaction with a canonical EF-hand protein, α-parvalbumin (α-PA). Evaluation of the equilibrium metal association constants for the active Ca binding sites of recombinant human α-PA ('CD' and 'EF' sites) from fluorimetric titration experiments and isothermal titration calorimetry data gave 4 × 10 M and 4 × 10 M for Ca, and 2 × 10 M and 2 × 10 M for Sr.

Host-Guest Complexation of Cucurbit[7]Uril and Cucurbit[8]Uril with the Antineoplastic and Multiple Sclerosis Agent Mitoxantrone (Novantrone).

The nature of interactions between the neutral/protonated mitoxantrone and the cucurbit[]uril ( = 7, 8) host system was analyzed by employing density functional theory calculations. A comparison between the inclusion complexes of CB[7] and CB[8] shows various subtle differences in the complexation thermodynamics, given as changes in the Gibbs energy. Doubly and quadruply charged mitoxantrone (MX) molecules spontaneously form complexes in a water solvent, which are modeled using the polarizable continuum model approach.

Zinc and Its Critical Role in : Insights from DFT/SMD Calculations.

Metal cations are required for the proper function of a great amount of biological processes, as they are indispensable cofactors participating in up to 40% of the active sites of the proteins. In the case of some diseases, however, metal cations could exhibit a dual function. As an example, the role of the zinc cation in the development of could be given.

Complexation of biologically essential (mono- and divalent) metal cations to cucurbiturils: a DFT/SMD evaluation of the key factors governing the host-guest recognition.

Supramolecular complexes based on classical synthetic macrocyclic host molecules such as cyclodextrins and calixarenes have received much attention recently due to their broad applications as biological and chemical sensors, bioimaging agents, drug delivery carriers, light-emitting materials, Cucurbit[]urils comprise another group of cavitands known for their high affinity for various guest molecules. Nonetheless, some aspects of their coordination chemistry remain enigmatic. Although they are recognized as potential biomimetic scaffolds, they are still not tested as metalloenzyme models and not much is known about their metal-binding properties.

Water inside β-cyclodextrin cavity: amount, stability and mechanism of binding.

Cyclodextrins (CDs) are native host systems with inherent ability to form inclusion complexes with various molecular entities, mostly hydrophobic substances. Host cyclodextrins are accommodative to water molecules as well and contain water in the native state. For β-cyclodextrin (β-CD), there is no consensus regarding the number of bound water molecules and the location of their coordination.

Host-guest interactions between -sulfonatocalix[4]arene and -sulfonatothiacalix[4]arene and group IA, IIA and f-block metal cations: a DFT/SMD study.

The molecular recognition in aqueous solution is extremely important because most biological processes occur in aqueous solution. Water-soluble members of the calix[]arene family (e.g.

α-Cyclodextrin: How Effectively Can Its Hydrophobic Cavity Be Hydrated?

Cyclodextrins (CDs) are among the most widely used native host systems with ability to form inclusion complexes with various molecular objects. This ability is so strong that the "hydrophobic" CD cavity never remains empty, even in the guest-free state it is filled with water molecules. However, no consensus has been reached concerning both the total number of hydrating water molecules and their preferred binding location in the CDs.