Can H2 be Superacidic? A Computational Study of Triel-Bonded Brønsted Acids.

The abundance of XIII group element compounds in science and industry together with their electron-deficient character gives rise to their influence on properties of the systems they interact with. This paper is an attempt to assess the strength, nature, and effect of formation of a triel bond on acidity. A wide set of Brønsted acids among others comprising hydrocarbons, halogen hydrides, and amines bonded with B, Al, and Ga trifluorides forming HX/TF3 was selected for the research. Various computational approaches (e.g., MP2, GFN2-xTB, SAPT2 + 3(CCD)δMP2, quantum theory of atoms in molecules analysis, and density overlap regions indicator) are used to describe the triel-bonded systems. Among other things, it was found that the electrostatics may not be the dominant contribution to the triel binding in some cases. Additionally, it was established that even weak Brønsted acids such as C2H2 or H2 may be superacidic if bonded to a Lewis acid (TF3) that is strong enough. The calculations indicate a significant covalent character of some of the studied HX/TF3 triel-bonded systems. Moreover, the effect of solvation of HX with TF3 as well as that of the reverse process on the acidity of the resulting system is thoroughly described.

Exploring novel Cd(II) complexes with 5-methyl-4-imidazolecarboxaldehyde: synthesis, structure, computational insights, and affinity to DNA through switchSense methodology.

A series of four Cd(II) complexes with 5-methyl-4-imidazolecarboxaldehyde (L) with different inorganic anions within or outside the coordination sphere of general formula: [CdCl2L2] (1), [CdBr2L2] (2), [CdI2L2] (3), and [CdL4](PF6)2·3H2O (4) was synthesized through one-step and two-step reactions, respectively. All complexes were obtained as colorless crystals without the need for recrystallization and exhibited solubility in aqueous solutions. Structural analysis revealed different coordination environments for each complex, with variations in bond lengths and angles. The crystal packing of the complexes was stabilized by hydrogen bonding and π-π stacking interactions. FT-IR analysis indicated coordination of the ligand to the metal ion, and UV-Vis studies confirmed the stability of the complexes in solution. Computational analysis has revealed the polar nature of the complexes and their favorable stability constants. Affinity studies with DNA using the switchSense technique demonstrated rapid association and dissociation processes for all complexes, with temperature-dependent binding constants. Thermodynamic analysis suggested spontaneous with positive entropy change and endothermic formation processes for the complexes. Overall, the study underscores the synthesis, examination, and interaction with DNA of Cd(II) complexes, demonstrating their promise within medicinal chemistry.

Application of a modern theoretical approach to the study of the interaction of KR-12 peptides derived from human cathelicidins with Cu(II) ions.

The human cationic antimicrobial protein (hCAP) corresponding to the overlapping sequences of 151-162 of hCAP named KR-12 peptide is the smallest portion of the only type of human Cathelicidin, which has been shown to be modifiable into a more effective antimicrobial. In this study, an in silico analysis, supported by potentiometric titration and isothermal titration calorimetry techniques, was performed to identify potential Cu(II) binding sites of KR-12. The analysis of the presented data at the given theoretical level (GFN2-xTB/ALPB) revealed which peptide chain fragments are involved in the most favourable KR-12-Cu(II) binding mode. Based on a quantum chemical approach, the most favourable coordination modes of Cu(II) to peptides are proposed together with the discussion of the chemical nature of the interactions. The presented results demonstrated that KR-12 interacts with metal ions mostly via the main chain's oxygen atoms; however, the two types of amino acids that are expected to be vital for the interaction of Cu(II) are D (aspartic acid) and R29 (arginine). It was demonstrated that in order to explain the complexity of the interaction process in peptide-metal ion systems, the use of theoretical methods is sometimes necessary to explain the details of the experimental results and provide an in-depth understanding of these dynamic systems.

Exploring the interaction of biologically active compounds with DNA through the application of the SwitchSense technique, UV-Vis spectroscopy, and computational methods.

DNA is a key target for anticancer and antimicrobial drugs. Assessing the bioactivity of compounds involves in silico and instrumental studies to determine their affinity for biomolecules like DNA. This study explores the potential of the switchSense technique in rapidly evaluating compound bioactivity towards DNA. By combining switchSense with computational methods and UV-Vis spectrophotometry, various bioactive compounds' interactions with DNA were analyzed. The objects of the study were: netropsin (as a model compound that binds in the helical groove), as well as derivatives of pyrazine (PTCA), sulfonamide (NbutylS), and anthraquinone (AQ-NetOH). Though no direct correlation was found between switchSense kinetics and binding modes, this research suggests the technique's broader utility in assessing new compounds' interactions with DNA. used as analytes whose interactions with DNA have not been yet fully described in the literature.

Theoretical Study on the Alkylimino-Substituted Sulfonamides with Potential Biological Activity.

Antibiotics play a key role in the fight against bacterial diseases. However, bacteria quickly learn how to minimize the effects of antibiotics and strengthen their resistance. Thus, the fight against them becomes more and more difficult and there is a constant search for new bactericidal compounds. It is important in this type of search to determine the basic properties of compounds such as pKa, hydrogen bond formation, or hydrophobicity. Here, we present the results of our in silico study of five sulfonamide derivatives differing in alkylamine substituent length. Based on our results, we propose a model of three possible pKa values for each of the studied compounds. Interestingly, the use of Muckerman's approach for pKa determination exhibits that theoretical and experimental results are in very good agreement. Intramolecular hydrogen bond formation affects pKa. The strength of the H-bond interaction increases from ethyl to butylamine and then decreases with the elongation of the alkylamine chain. The obtained partition coefficients (expressed here in the value of log P) increase with the number of carbon atoms in the alkylamine chain following Lipinski's rule of five. The presented results provide important structural, physicochemical, and thermodynamic information that allows for the understanding of the influence of some sulfonamides and their possible activity.

Aluminabenzene-based Lewis superacids and weakly coordinating anions.

Quantum-chemical calculations were used to describe both the acidity of aluminabenzene-based Lewis acids and stability of aluminabenzene-based anions. Aluminabenzene itself was found to exhibit greater acidity than antimony pentaflouride, and thus can be qualified as a Lewis superacid. Substitution of the heterocyclic ring with electron withdrawing groups results in formation of extremely strong Lewis superacids. Two of them, namely AlC5 Cl5 and AlC5 (CN)5 are the strongest Lewis acids described in the literature so far. Whereas, anions formed after the addition of fluoride anion to substituted aluminabenzene-based Lewis acids, while characterized by somewhat lower electronic stability than the least coordinating anions hitherto known, are considerably more stable in terms of thermodynamic stability (measured by the propensity to electrophile attack). On this account they are expected to act as counterions for the most reactive cations. The proposed Lewis acids may be prone to the isomerization and dimerization, whereas studied anions are expected to be stable with regard to such processes.

Macrocyclic chemosensors with anthraquinone signaling unit built into ionophore. Experimental and computational studies (part I) - synthesis and effect of proton binding on spectrophotometric and electrochemical properties.

Two macrocyclic chemosensors with anthraquinone signaling unit incorporated into ionophore system (via positions 1 and 8) have been synthesized and subsequently their physicochemical properties became the subject of our extensive research. First ligand, labeled in the paper as AQ-Ncrown is characterized by a cyclic structure of a crown ether, while second one AQ-Ncrypt includes an additional ethoxy bridge, which ensures the bicyclic character of a cryptand. The studied macrocycles possess both oxygen and nitrogen heteroatoms in the ionophore cavity. Dualistic (chromophore and electrophore) signaling nature of described compounds, makes them potentially attractive molecular recognition systems. The aim of our research was to synthesize and analyze the spectroscopic, acid-base and redox properties of aforesaid macrocycles. Furthermore, we have combined experimental approach together with theoretical investigations. The equilibrium structures of AQ-Ncrown and AQ-Ncrypt were determined with the use of DFT calculations. The sensitivity of studied macrocycles towards interactions with protons was scrutinized. The complete pH-spectrophotometric characteristic of studied ligands together with their protolytic forms and corresponding pKa values were determined. The influence of medium (aprotic and protic solvent) on spectral effects was described. Furthermore, the molecular electrostatic potential maps for ligands and differential electron densities for their mono and dianions were calculated. The redox reactions was investigated at different pHs by cyclic voltammetry. Electrochemical results have presented intriguing phenomenon: the specific stabilization of the reduced form of the protonated molecules. The calculations have revealed that this is a consequence of barrierless intramolecular proton transfer (from the macrocycle cavity onto the anthraquinone moiety) that might occur during the reduction process in acidic medium.

Application of the SwitchSense Technique for the Study of Small Molecules' (Ethidium Bromide and Selected Sulfonamide Derivatives) Affinity to DNA in Real Time.

The discovery and introduction of the switchSense technique in the chemical laboratory have drawn well-deserved interest owing to its wide range of applications. Namely, it can be used to determine the diameter of proteins, alterations in their tertiary structures (folding), and many other conformational changes that are important from a biological point of view. The essence of this technique is based on its ability to study of the interactions between an analyte and a ligand in real time (in a buffer flow). Its simplicity, on the other hand, is based on the use of a signaling system that provides information about the ongoing interactions based on the changes in the fluorescence intensity. This technique can be extremely advantageous in the study of new pharmaceuticals. The design of compounds with biological activity, as well as the determination of their molecular targets and modes of interactions, is crucial in the search for new drugs and the fight against drug resistance. This article presents another possible application of the switchSense technique for the study of the binding kinetics of small model molecules such as ethidium bromide (EB) and selected sulfonamide derivatives with DNA in the static and dynamic modes at three different temperatures (15, 25, and 37 °C) each. The experimental results remain in very good agreement with the molecular dynamics docking ones. These physicochemical insights and applications obtained from the switchSense technique allow for the design of an effective strategy for molecular interaction assessments of small but pharmaceutically important molecules with DNA.

Metal-Ion Interactions with Dodecapeptide Fragments of Human Cationic Antimicrobial Protein LL-37 [hCAP(134-170)].

Isothermal titration calorimetry, circular dichroism (CD) techniques, and in silico analysis were used to determine potential metal binding sites in human cationic antimicrobial protein (hCAP) corresponding to overlapping the dodecapeptide sequences of hCAP(134-170) referred to as LL-37. The correct antibacterial action of LL-37 is closely related to its established unique structure. Disturbances in the LL-37 structure (e.g., unwanted presence of metal ions) lead to a radical change in its biological functions. Five fragments of the LL-37 [hCAP(134-170)], namely, hCAP(134-145) (A1), hCAP(140-151) (A2), hCAP(146-157) (A3), hCAP(152-163) (A4), and hCAP(159-170) (A5), were taken into account and their affinity to Mn(II) and Zn(II) ions was rigorously assessed. We prove that only three of the investigated peptides (A1, A2, and A5) are capable of forming thermodynamically stable complexes with metal ions. Additionally, based on density functional theory (DFT) calculations, we propose the most likely coordination modes of metal(II) to peptides as well as discuss the chemical nature of the interactions. Finally, we present the structural features of the strongest binding peptide, hCAP(159-170), responsible for the metal binding. The presented results provide important structural and thermodynamic information to understand the influence of some metal ions on the activity of hCAP(134-170).

Non-Valence Anions of Pyridine and the Diazines.

The dipole-bound anions of pyridine, pyridazine, and pyrimidine are characterized using equation of motion coupled cluster singles and doubles calculations. These calculations predict that the anions of pyridine, pyrimidine and pyridazine are bound in the Born-Oppenheimer approximation by 0.05, 0.8, and 19.0 meV, respectively. The binding energies of pyrimidine and pyridazine are large enough that the anions will remain bound even when allowing for corrections to the Born-Oppenheimer approximation, while that of pyridine is a borderline case. We were unable to find a stable non-valence correlation-bound anion for pyrazine, which has a zero dipole moment.

The influence of tetrel bonds on the acidities of group 14 tetrafluoride - inorganic acid complexes.

Ab initio methods were used to determine the influence of tetrel bond formation on the acidity. The systems composed of inorganic acids and tetrafluorides of 14 group elements have been tested - HA/EF4 , where HA = H2 O, NH3 , HF, HCN, HNC, HCNO, HOCN and E = C, Si, Ge, Sn or Pb. It turns out that the electron density flow involved with formation of tetrel bond to carbon-based systems leads to negligible increase in acidity. In the case of the acceptor compounds based on the remaining 14 group elements however, the effect is much more apparent, as most of those compounds may be considered a Brønsted superacids. The electronic stability of anions formed after the deprotonation of aforementioned complexes has been investigated. Vast majority of the anions were found to exhibit significant electron binding energies.

An Excess Electron Bound to Magnesium Halides and Basic Grignard Compounds (RMgX and RMgR, R = Me, Et, Ph; X = F, Cl, Br).

Grignard reagents are commonly used in organic synthesis, yet their ability to form stable anionic states has not been recognized thus far. In this work, representative examples of RMgF, RMgCl, and RMgBr molecules involving methyl, ethyl, and phenyl functional groups serving as R substituents are investigated regarding their equilibrium structures, adiabatic electron affinities, and vertical electron detachment energies of their daughter anions. The electronic stabilities determined for the negatively charged Grignard compounds are then compared to those predicted for their corresponding magnesium halides. The anions formed by RMgX (R = Me, Et, Ph; X = F, Cl, Br) molecules are found to be adiabatically electronically stable valence-bound systems characterized by relatively large vertical electron detachment energies spanning the 0.79-1.62 eV range. In addition, significant structural relaxation upon attachment of an excess electron is predicted for all Grignard compounds considered. Furthermore, the re-examination of the anions formed by magnesium halides resulted in recognizing them as valence-bound rather than dipole-bound anions, in contrast to the earlier interpretations.

Caralumane Superacids of Lewis and Brønsted Character.

Carborane Brønsted superacids have proven to be useful reagents in a variety of organic and inorganic synthetic processes. In this work, analogs in which the icosahedral CB11 carborane core is replaced by a CAl11 core are studied using ab initio electronic structure tools. Each so-called caralumane Brønsted acid is formed by adding HF, HCl, or HH to a corresponding caralumane Lewis acid possessing a vacant Al-centered orbital that acts to accept an electron pair from the HF, HCl, or HH. The Lewis acid strengths of the species involved, as measured by their F- ion affinities, are all found to exceed the threshold for labeling them Lewis superacids. Also, the deprotonation Gibbs free energies of the Brønsted acids are found to be small enough for them to be Brønsted superacids. When HF or HCl is bound to a caralumane Lewis acid to form the Brønsted acid, the HF or HCl is bound datively to a single Al atom, and hydrogen bonds can be formed between this molecule's H atom and nearby F or Cl atoms attached to other Al atoms. In contrast, when HH is bound to the Lewis acid to form the Brønsted acid, two novel low-energy structures arise, both of which are Brønsted superacids. One has an essentially intact HH molecule attached to a single Al atom in a η2 fashion. In the other, the HH molecule is heterolytically cleaved to generate a hydride ion that attaches to a single Al atom and a proton that binds in a multicenter manner to other Al atoms. The structures and relative energies of a multitude of such caralumane Lewis and Brønsted superacids are provided and discussed.

Icosahedral Carborane Superacids and their Conjugate Bases Comprising H, F, Cl, and CN Substituents: A Theoretical Investigation of Monomeric and Dimeric Cages.

Theoretical investigation of the H(CHB11 X11 ) (X=H, F, Cl, CN), H(CHB11 Xn Y11-n ) (X,Y=F, Cl; n=1,5), and dimeric (H(CHB11 X11 ))2 (X=F, Cl) carborane superacids performed at the B3LYP/6-311++G(d,p) theory level revealed the similarity of their equilibrium structures and the possibility of nearly barrierless hydrogen atom migration among the substituents attached to one side of the icosahedral CB11 cage. The vertical electron detachment energies predicted at the OVGF/6-311++G(3df,2pd) theory level for the conjugate bases (CHB11 X11 )- were found to span the 5.82-9.00 ev range. The acid strengths (manifested by the Gibbs free deprotonation energies spanning the 213-266 kcal/mol range) predicted for the icosahedral H(CHB11 X11 ) carborane systems confirm their superacidic properties which might be increased even further by the attachment of the second carborane H(CHB11 X11 ) unit that leads to a dimeric structure mimicking a part of an experimentally observed H-bridged polymeric chain. The Gibbs free deprotonation energy of the dimeric (H(CHB11 Cl11 ))2 acid was predicted to be smaller by 17 kcal/mol than that of the corresponding monomeric H(CHB11 Cl11 ) acid.

The mechanisms of isobutene hydration yielding tert-butanol catalyzed by a strong mineral acid (H2SO4) and Lewis-Brønsted superacid (HF/SbF5).

The mechanism of the (CH3)2CCH2+H2O→(CH3)3COH reaction catalyzed by two strong acids (H2SO4 and HSbF6) was investigated theoretically using the ab initio MP2 and CCSD(T) methods and the aug-cc-pVDZ/LANL2DZ and aug-cc-pVTZ/LANL2DZ basis sets. The effects of surrounding solvent molecules were approximated by employing the polarized continuum solvation model. The most important findings include the observation that both acids are capable of catalyzing isobutene hydration but the reaction is predicted to proceed faster when the HSbF6 superacid plays the catalyst role.

The Acid Strength of the Lewis-Brønsted Superacids - A QSPR Study.

The acidity of Lewis-Brønsted superacids can be derived from the theoretical calculations as the Gibbs free energy of the deprotonation reaction (ΔGacid ), which describes the tendency of a studied compound to donate a proton. This paper presents the first Quantitative Structure - Property Relationship (QSPR) model that correlates the ΔGacid of superacid (HF/MeX3 formula (X=F, Cl, Br)) with their structure. Developed model is well fitted, roubustness, has good predictive abilities, fulfills all OECD recommendation for good model. Obtained results provide the insight into the relation of structural features of superacids, which are responsible for their acid strength - the structures characterized by strong F-Me dative bond (with relatively large vibrational frequency), small positive partial atomic charge on Me central atom, possibly large polarity exhibit large acid strength. Such assumption can be used in the future as valuable information in the process of the designing new, stronger, more effective superacids.

Formation of Enormously Strongly Bound Anionic Clusters Predicted in Binary Superacids.

The possible formation of the (AlF4(HF) n)- ( n = 1-8 and 12), (AsF6(HF) n)-, and (SbF6(HF) n)- ( n = 1-6 and 12) anionic clusters of a superhalogen nature is predicted in the solutions of binary HF/AlF3, HF/AsF5, and HF/SbF5 Lewis-Brønsted superacids on the basis of ab initio calculations. Our results show that all systems investigated represent extremely strongly bound anions characterized by vertical electron detachment energies (VDEs) that significantly exceed 10 eV. The VDE values estimated for the (AlF4(HF)12)-, (AsF6(HF)12)-, and (SbF6(HF)12)- systems are predicted to be 13.96, 14.03, and 14.03 eV, respectively, and are the largest vertical electron detachment energies reported in the literature thus far.