Complex Non-covalent Interactions Research Articles

3-(2-pyridyl)-5-(4-chlorophenyl)-1,2,4-triazine as a ligand: Synthesis of three lead(II) complexes, a spectroscopic and structural study using experimental and theoretical methods

Three new Pb(II) complexes of the ligand 3-(2-pyridyl)-5-(4-chlorophenyl)-1,2,4-triazine (pcpt) and different anionic co-ligands (1: bromide, 2: iodide and 3: isothiocyanate) were synthesized and characterized by elemental (CHN) analysis, FT-IR and 1H NMR spectroscopy and single crystal X-ray diffraction (SC-XRD). Considering only strong primary coordination bonds, the Pb(II) centres in complexes 1 and 2 are holodirectionally and in 3 hemidirectionally coordinated by the organic pcpt ligands due to stereochemical inactivity (1, 2) and activity (3) of the lone electron pair. The primary coordination sphere in 3 is sterically suitable for establishing interactions at longer distances, where the Pb centre acts as Lewis acid. Thus, all the Pb centers participate in Pb⋅⋅⋅Cl tetrel interactions, which together with secondary interactions of the ligands extend the structures into 1D supramolecular assemblies. A Hirshfeld surface inspection, along with the natural bond analysis (NBO), quantum theory of atoms in molecules (ATAIM), molecular electrostatistic potential (MEP) surface, and theoretical vibrational analysis at B3LYP/Def2-TZVP level of theory were conducted for the sake of further investigation of the non-covalent interactions in complexes 1–3. An enrichment ratio is also calculated for the chemical species to determine the tendency of their interactions in the crystal packing. The theoretical values obtained from the DFT at B3LYP/Def2-TZVP level of theory ensure that the expected consequences match the experimental findings. The QTAIM calculations allow the estimation of the strength of the primary and secondary/tetrel interactions and to propose the theoretical criteria based on the |VBCP|/GBCP, HBCP/ρBCP, and DI parameters for distinguishing the interactions. The MEP calculations confirmed the presence of a σ-hole in the proximity of the PbII centers.

Cellulose Dissolution, Modification, and the Derived Hydrogel: A Review.

The cellulose-based hydrogel has occupied a pivotal position in almost all walks of life. However, the native cellulose can not be directly used for preparing hydrogel due to the complex non-covalent interactions. Some literature has discussed the dissolution and modification of cellulose but has yet to address the influence of the pretreatment on the as-prepared hydrogels. Firstly, the "touching" of cellulose by derived and non-derived solvents was introduced, namely, the dissolution of cellulose. Secondly, the "conversion" of functional groups on the cellulose surface by special routes, which is the modification of cellulose. The above-mentioned two parts were intended to explain the changes in physicochemical properties of cellulose by these routes and their influences on the subsequent hydrogel preparation. Finally, the "reinforcement" of cellulose-based hydrogels by physical and chemical techniques was summarized, viz., improving the mechanical properties of cellulose-based hydrogels and the changes in the multi-level structure of the interior of cellulose-based hydrogels.

De novo design of a β-lactamase in a modular helical bundle protein scaffold

The advancements in computational methods and understanding of protein structure and function has led to significant progress in the design of functional proteins. However, the de novo design of enzymes remains an ongoing challenge due to the difficulty of building complex non-covalent interactions into a preorganized and substrate-accessible active site. Helical bundles are a highly designable and parameterizable protein scaffold that has shown great promise in the design of functional proteins such as metal, cofactor, and some small-molecule binding, but there has been limited success with the design of organocatalysts.

Antimicrobial activities of cadmium (II) and nickel (II) complexes containing pyridine ring: Investigation of crystallographic, spectroscopic, Hirshfeld surface analysis, and TD/DFT calculations

AbstractTwo complexes [Cd(L)2(NO3)2] (1) and [Ni(L)2(OH)2][Ni(L)2(CH3OH)2](NO3)2·CH3OH (2) (L = 2‐[2‐pyridyl]‐4‐methyl‐1,2‐dihydroquinazolin 3‐oxide) were gained via complexation an amount of the new ligand L with different nitrate salts. The obtained complexes were characterized by elemental analysis, spectroscopy, and X‐ray crystallographic. In the crystal structure, centrosymmetric 1 adopted slightly distorted octahedral geometry. On the other hand, the independent unit of 2 contained two half Ni (II) complex located on a center of symmetry, differing for the axial ligand, two uncoordinated nitrate ions, and one lattice methanol molecule. Both the crystal structures formed a 3‐D supramolecular architecture through different interactions (H‐bonds, π···π, etc). X‐ray crystallography revealed that complexes 1 and 2 had 2:1 ligand‐to‐metal ratios. Most strikingly, 1 performed different fluorescence behaviors in diverse solvents, whereas 2 exhibited fluorescence quenching. When 1 was dissolution in N,N‐dimethylformamide (DMF) solvent system, it has better fluorescence properties. The geometry optimization and HOMOs and LUMOs energies of both complexes were calculated by density functional theory (DFT) methods, and the nucleophilic and electrophilic attack sites were confirmed with electrostatic potential (ESP) calculations. Preliminary investigation of antimicrobial activities of all compounds against Gram‐negative bacteria (Escherichia coli) and Gram‐positive bacteria (Bacillus subtilis) was reported. Additionally, CrystalExplorer program was used to quantify the noncovalent interactions in complexes 1 and 2 through Hirshfeld surface analysis.

Achieving Efficient n-Doping of Conjugated Polymers by Molecular Dopants.

ConspectusMolecular doping is one of the most central propositions in the field of organic electronics. Unlike classical inorganic semiconductors doped by atomic substitution, organic conjugated materials react with molecular dopants, and then intermolecular charge transfer is involved within. Therefore, the complex noncovalent interactions between two components often cause the molecular dopant to destroy the orderly stacking of the host organic materials and reduce the original properties of the material, such as carrier mobility, which here we call the "doping dilemma." Recently, many studies focus on improving p-doping efficiency and electrical conductivity of doped conjugated polymers; however, the development of n-type molecular doping currently lags far behind that of its p-counterpart. It is well-known that both efficient p- and n-type molecular doping are indispensable in various organic electronic devices, including light-emitting diodes, photovoltaics, field-effect transistors, and thermoelectrics. It is thus an urgent requirement to achieve efficient n-doping in conjugated polymers.In this Account, we give a brief overview of our efforts to improve the n-doping efficiency in conjugated polymers with several strategies from the aspects of the polymer/dopant molecular design and the exploration of the n-type molecular doping mechanism and charge transport mechanism in n-doped organic materials. For the conjugated polymer engineering, we first demonstrate that increasing the electron affinity of the host polymer through halogen substitution can boost the n-doping efficiency. Still, the rigid coplanar backbones of conjugated polymers play a crucial role in the polaron delocalization and final electrical performance. In addition, we emphasize the importance of morphology control in the doped polymers to address the "doping dilemma." For n-dopants designing, we summarize some basic guidelines from molecular sizes and shapes, the interaction between dopants (or dopant cations) and polymers, and the effects of dopants on morphology to design high-efficacy n-type molecular dopants. We propose that the polymers and the dopants need to be treated as a whole system; while enhancing the ionization efficiency, more attention should be paid to the carrierization (free-carrier generation) efficiency of these binary systems. In the end, we adopt the n-type polymer thermoelectric material as an example to discuss the grand challenges encountered in practical applications of n-doped conjugated polymers. The air stability and micrometer-thick thermo-leg processing of n-doped polymers are highlighted for thermoelectric applications. It is our hope that this Account showcases a blueprint for rational approaches and a deep understanding toward the design and development of efficient n-doping in conjugated polymers, bringing n-doped organic materials into the next era.

DFT investigations of linear Zn3-type complex with compartmental N/O-donor Schiff base: Synthesis, characterizations, crystal structure, fluorescence and molecular docking

A linear Zn(II) complex, [Zn3(LOMe-pn)2(ƞ1-NCS)2] (1) containing a N2O2O′2 donor Schiff base, (H2LOMe-pn = N, N-bis(3-methoxysalicylidene)-2, 2-dimethylpropane-1, 3 diamine) has been synthesized and structurally well characterized. SCXRD study reveals that in 1, the asymmetric section contains two identical discrete unit and each discrete unit contains three zinc metal ions (Zn1, Zn2 and Zn3) which are crystallographic independent, two deprotonated ligands [LOMe-pn]2- and [SCN−] ions which are linked with only terminal zinc ion in a η1 mode where terminal zinc atoms (Zn1/Zn3) are distorted square pyramidal while Zn2 is square antiprismatic. All computational calculations were performed by the DFT/M06 functional level and the 6-31G * basis set in the ground state. Complex optimized structure, HOMO-LUMO energy gap, Hirshfeld surface, MEP and NLO property was nicely explained with the help of DFT. Total dipole moment, average polarizability and first hyperpolarizability were calculated where α and βhyp values are well demonstrate the NLO property of complex (1). In addition, Bader’s “atoms-in-molecules” was analysed to delineate complex non-covalent interactions using the same level of theory. Experimental electronic spectra were explained using TD-DFT level of calculations with an IEFPCM solvent model. DMF solvent explore complex (1) is a fluorescent material with maximum emission at 479 nm at an excitation wavelength of 300 nm. Finally, molecular docking was executed with cytochrome P450 from B. megaterium and M. tuberculosis. Results of molecular docking and HOMO-LUMO energy gap can provide new insights in the development of antimycobacterial drugs and next-generation semiconductor devices.

Could Quantum Mechanical Properties Be Reflected on Classical Molecular Dynamics? The Case of Halogenated Organic Compounds of Biological Interest.

Essential to understanding life, the biomolecular phenomena have been an important subject in science, therefore a necessary path to be covered to make progress in human knowledge. To fully comprehend these processes, the non-covalent interactions are the key. In this review, we discuss how specific protein-ligand interactions can be efficiently described by low computational cost methods, such as Molecular Mechanics (MM). We have taken as example the case of the halogen bonds (XB). Albeit generally weaker than the hydrogen bonds (HB), the XBs play a key role to drug design, enhancing the affinity and selectivity toward the biological target. Along with the attraction between two electronegative atoms in XBs explained by the σ-hole model, important orbital interactions, as well as relief of Pauli repulsion take place. Nonetheless, such electronic effects can be only well-described by accurate quantum chemical methods that have strong limitations dealing with supramolecular systems due to their high computational cost. To go beyond the poor description of XBs by MM methods, reparametrizing the force-fields equations can be a way to keep the balance between accuracy and computational cost. Thus, we have shown the steps to be considered when parametrizing force-fields to achieve reliable results of complex non-covalent interactions at MM level for In Silico drug design methods.

Noncovalent Interactions in Complexes Involving the Cyclic C2H2X (X=O, S, Se) Molecules and the Lewis Acids YF (Y=F, Cl, Br, H)

AbstractA computational study of the cyclic Lewis bases C2H2X (X=O, S, Se) interacting with the Lewis acids YF (Y=F, Cl, Br, H) in model C2H2X…YF dyads was undertaken. It was shown that the noncovalent X…Y interaction in these binary complexes increases with increasing YF dipole moment for the C2H2O complexes, but not for the C2H2S and C2H2Se complexes, where instead the X…Y interaction increases with increasing X/Y electronegativity difference. This suggests that electrostatic forces dominate the binding in the former, whereas polarization effects dominate in the latter complexes. These explanations were supported by natural bond orbital (NBO) and atoms in molecules (AIM) analyses of the electron density, as well as interaction energy decomposition analyses. A subsequent study of the cooperative effect of an additional hydrogen bond in the model triads, FH…C2H2X…YF and C2H2X…YF…HF, found that the X…Y interaction in the dyads is weakened in the former and strengthened in the latter, with the trends identified in the dyads persisting in both triads.

Quantifying the Effects of Hydrogen Bonding on Nitrile Frequencies in GFP: Beyond Solvent Exposure.

Vibrational spectroscopy is a powerful tool for characterizing the complex noncovalent interactions that arise in biological systems. The nitrile stretching frequency has proven to be a particularly convenient biological probe, but the interpretation of nitrile spectroscopy is complicated by its sensitivity to local hydrogen bonding interactions. This often inhibits the straightforward interpretation of nitrile spectra by requiring knowledge of the molecular-level details of the local environment surrounding the probe. While the effect of hydrogen bonds on nitrile frequencies has been well-documented for small molecules in solution, there have been relatively few studies of these effects in a complex protein system. To address this, we introduced a nitrile probe at nine locations throughout green fluorescent protein (GFP) and compared the mean vibrational frequency of each probe to the specific hydrogen bonding geometries observed in molecular dynamics (MD) simulations. We show that a continuum of hydrogen bonding angles is found depending on the particular location of each nitrile, and that the differences in these angles account for the differences in the measured nitrile frequency. We further observed that the temperature dependence of the nitrile frequencies (measured as a frequency-temperature line slope, FTLS) was a good indicator of the hydrogen bonding interactions of the probe, even in scenarios where the nitrile was involved in complex and restricted hydrogen bonds, both from protein and from water. While constant offsets to the nitrile frequency to all hydrogen bonding environments have been applied before to interpret shifts in nitrile frequency, we show that this is insufficient in systems where the hydrogen bonds may be restricted by the surrounding medium. However, the strength of the observed correlation between nitrile frequency and hydrogen bonding angle suggests that it may be possible to disentangle electrostatic effects and effects of the orientation of hydrogen bonding on the nitrile stretching frequency. Meanwhile, the experimental measurement of the FTLS of the nitrile is an excellent tool to identify changes in the hydrogen bonding interactions for a particular probe.

Nanoparticle-Protein Interactions: Therapeutic Approaches and Supramolecular Chemistry.

Research on nanoparticles has evolved into a major topic in chemistry. Concerning biomedical research, nanoparticles have decisively entered the field, creating the area of nanomedicine where nanoparticles are used for drug delivery, imaging, and tumor targeting. Besides these functions, scientists have addressed the specific ways in which nanoparticles interact with biomolecules, with proteins being the most prominent example. Depending on their size, shape, charge, and surface functionality, specifically designed nanoparticles can interact with proteins in a defined way. Proteins have typical dimensions of 5-20 nm. Ultrasmall nanoparticles (size about 1-2 nm) can address specific epitopes on the surface of a protein, for example, an active center of an enzyme. Medium-sized nanoparticles (size about 5 nm) can interact with proteins on a 1:1 basis. Large nanoparticles (above 20 nm) are big in comparison to many proteins and therefore are at the borderline to a two-dimensional surface onto which a protein will adsorb. This can still lead to irreversible structural changes in a protein and a subsequent loss of function. However, as most cells readily take up nanoparticles of almost any size, it is easily possible to use nanoparticles as transporters for proteins into a cell, for example, to address an internal receptor. Much work has been dedicated to this approach, but it is constrained by two processes that can only be observed in living cells or organisms. First, nanoparticles are usually taken up by endocytosis and are delivered into an intracellular endosome. After fusion with a lysosome, a degradation or denaturation of the protein cargo by the acidic environment or by proteases may occur before it can enter the cytoplasm. Second, nanoparticles are rapidly coated with proteins upon contact with biological media like blood. This so-called protein corona influences the contact with other proteins, cells, or tissue and may prevent the desired interaction. Essentially, these effects cannot be understood in purely chemical approaches but require biological environments and systems because the underlying processes are simply too complicated to be modeled in nonbiological systems. The area of nanoparticle-protein interactions strongly relies on different approaches: Synthetic chemistry is involved to prepare, stabilize, and functionalize nanoparticles. High-end analytical chemistry is required to understand the nature of a nanoparticle surface and the steps of its interaction with proteins. Concepts from supramolecular chemistry help to understand the complex noncovalent interactions between the surfaces of proteins and nanoparticles. Protein chemistry and biophysical chemistry are required to understand the behavior of a protein in contact with a nanoparticle. Finally, all chemical concepts must live up to the "biological reality", first in cell culture experiments in vitro and finally in animal or human experiments in vivo, to open new therapies in the 21st century. This interdisciplinary approach makes the field highly exciting but also highly demanding for chemists who, however, have to learn to understand the language of other areas.

Exploiting non-covalent π interactions for catalyst design.

Molecular recognition, binding and catalysis are often mediated by non-covalent interactions involving aromatic functional groups. Although the relative complexity of these so-called π interactions has made them challenging to study, theory and modelling have now reached the stage at which we can explain their physical origins and obtain reliable insight into their effects on molecular binding and chemical transformations. This offers opportunities for the rational manipulation of these complex non-covalent interactions and their direct incorporation into the design of small-molecule catalysts and enzymes.

A bio-inspired design strategy: Organization of tryptophan-appended naphthalenediimide into well-defined architectures induced by molecular interactions

The chemistry of molecular assemblies involves weak yet complex non-covalent interactions, and the molecular organization of the π-conjugated material is crucial in determining the performance of an organic electronic device. Herein we demonstrate a bioinspired design strategy to tune the self-assembly of naphthalenediimides (NDIs) by minute structural variations, π-π stacking, hydrophobic interactions and metal interactions. We address some of the limitations associated with current design strategies, such as restriction to a specific molecular interaction or the difficulty in controlling the assembly due to several complicated intermolecular interactions. Hydrophobic-effect-induced J-type aggregation and sodium-interaction-induced H-type aggregation of tryptophan-appended NDIs have been illustrated. (1)H NMR spectra further reveal sodium cation-π interactions in tryptophan-appended NDIs, while NMR and IR spectroscopic studies confirm the structural variations associated with the molecular assembly. In summary, the molecular organization has been successfully transformed from nanospheres to particles, nanobelts, fibers and fractals. Such drastic changes in the morphology are clear and striking evidence of the importance of non-trivial weak non-covalent forces.

Halogen Bonding: A Study based on the Electronic Charge Density

Density functional theory (DFT) and atoms in molecules theory (AIM) were used to study the characteristic of the noncovalent interactions in complexes formed between Lewis bases (NH(3), H(2)O, and H(2)S) and Lewis acids (ClF, BrF, IF, BrCl, ICl, and IBr). In order to compare halogen and hydrogen bonds interactions, this study included hydrogen complexes formed by some Lewis bases and HF, HCl, and HBr Lewis acids. Ab initio, wave functions were generated at B3LYP/6-311++G(d,p) level with optimized structures at the same level. Criteria based on a topological analysis of the electron density were used in order to characterize the nature of halogen interactions in Lewis complexes. The main purpose of the present work is to provide an answer to the following questions: (a) why can electronegative atoms such as halogens act as bridges between two other electronegative atoms? Can a study based on the electron charge density answer this question? Considering this, we had performed a profound study of halogen complexes in the framework of the AIM theory. A good correlation between the density at the intermolecular bond critical point and the energy interaction was found. We had also explored the concentration and depletion of the charge density, displayed by the Laplacian topology, in the interaction zone and in the X-Y halogen donor bond. From the atomic properties, it was generally observed that the two halogen atoms gain electron population in response to its own intrinsic nature. Because of this fact, both atoms are energetically stabilized.