Dendrimer-tetrachloroplatinate precursor interactions. 1. Hydration of Pt(II) species and PAMAM outer pockets

Density functional theory is used to investigate the structure and energetics of the tetrachloroplatinate anion and its hydrolysis products at several degrees of hydration, as well as those of outer dendrimer pockets hosting such species. The number of water molecules able to saturate an unprotonated outer dendrimer pocket is found to be two, as inferred from calculated thermodynamic data. However, such a number could not be established for a protonated pocket where the dendrimer adopts a more open configuration. An analysis of possible pocket configurations is done on the basis of the orientations of the amide O atoms in the outer pockets. The effect of explicit water on the infrared spectra of the dendrimer pockets is reported and compared to experimental values.     

Noncovalent binding interactions of polyacrylamide and clay in nanocomposite hydrogels

The interactions between organic and inorganic components in pregel solution for polyacrylamide (PAAm)/clay nanocomposite hydrogels (NC gels) and in prepared NC gels are investigated. Besides, a kind of self‐crosslinked PAAm gels with excellent mechanical properties is fabricated in the absence of any cross‐linking agents, the hydrogen bonding interactions among PAAm chains are acted as the cross‐linking force. It is revealed that the binding interactions of PAAm and clay in NC gels are owing to the noncovalent interactions between amide groups on PAAm chains and clay platelets, which afford the cross‐linking force for NC gels network formation. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

Noncovalent interactions within a synthetic receptor can reinforce guest binding

Structural and thermodynamic data are presented on the binding properties of anion receptors containing two covalently linked cyclopeptide subunits that bind sulfate and iodide anions with micromolar affinity in aqueous solution. A synchrotron X-ray crystal structure of the sulfate complex of one receptor revealed that the anion is bound between the peptide rings of the biscyclopeptide. Intimate intramolecular contacts between the nonpolar surfaces of the proline rings of the individual receptor moieties in the complex suggest that hydrophobic interactions within the receptor that do not directly involve the guest contribute to complex stability. This finding is supported by a microcalorimetric analysis of the solvent dependence of complex stability, which showed that increasing the water content of the solvent has only a weak influence on the Gibbs energy of binding. Hence, the increasing amount of energy required for desolvating the binding partners in solutions containing more water is almost compensated by the increasingly favorable hydrophobic interactions. Further observations that suggest that guest-induced intra-receptor interactions contribute to guest binding are (i) anion binding of a monomeric cyclopeptide lacking the covalent linkage between the two rings leads to the formation of 2:1 complexes; (ii) in the crystal structure of the 2:1 iodide complex of this monotopic receptor, a similar arrangement of the two cyclopeptide rings has been found as in the sulfate complex of the biscyclopeptide; (iii) complex formation of the monomeric cyclopeptide in aqueous solution is highly cooperative with a large stability constant corresponding to the formation of the 2:1 complexes from relatively instable 1:1 complexes; (iv) the monomeric cyclopeptide forms only 1:1 anion complexes in DMSO where hydrophobic interactions do not take place; and (v) introducing polar hydroxy groups on the proline rings of the monomeric cyclopeptide disrupts cooperativity causing the formation of only 1:1 complexes even in aqueous solution. Taken together these observations demonstrate that, in addition to direct receptor-substrate interactions, noncovalent interactions between the two subunits of such biscyclopeptides contribute significantly to anion complex stability. Reinforcement of molecular recognition through intra-receptor interactions should be an attractive new strategy to boost host-guest affinities.     

Pt(II) uptake by dendrimer outer pockets: 2. Solvent-mediated complexation

We study the effect of the solvent (water) on the ligand exchange reaction (LER) step of Pt(II) complexation to PAMAM dendrimers. The results suggest that aquation of tetrachloroplatinate anion (PtCl(4)(2-)) inside PAMAM outer pockets occurs prior to its reaction with dendrimer atom binding sites. Thus, the active involvement of water opens up several pathways by which Pt(II) can bind to tertiary amine sites (N3). Monodentate binding pathways by which a PtCl(3)(-) moiety is obtained as a final product rather than PtCl(2)(H(2)O) are considered to be the predominant routes due to their smaller degree of complexity, including aspects such as less number of intermediates and lower energy barriers. Monodentate binding of Pt(II) to the secondary amide site (N2) is found to be feasible, in agreement with previous NMR experiments, once aquation of the tetrachloroplatinate anion has occurred. For this type of binding to occur, the dendrimer branch amide group configuration would have to switch from its equilibrium position (trans) to a cis position. It is also found that outer pockets aid Pt(II) complexation with the dendrimer mainly by making the noncovalent binding (NCB) step more favorable than that in branchless environments. Finally, our results predict that competitive monodentate binding of Pt(II) to either N3 or N2 is thermodynamically rather than kinetically driven.     

Noncovalent secondary interactions in Co(II)Salen complexes: O2 binding and catalytic activity in cyclohexene oxygenation

The O2 affinity of Co(II)Salen complexes 1-4 and their reactivity in cyclohexene oxygenation reactions of Co(II)Salen complexes 1-4 are modulated by noncovalent interactions such as hydrogen bonding and steric hindrance using a functionalized diamino bridge. Higher O2 affinity is observed in the case of efficient hydrogen-bonding interactions (complex 1), while increased steric hindrance (cis vs trans diamino bridge) around the Co-coordinated O2 is influencing the reactivity of the complexes.     

Noncovalent interactions and internal dynamics in dimethoxymethane-water

The millimeter-wave absorption and Fourier transform microwave spectra of five isotopologues of the 1:1 adduct of dimethoxymethane-water have been measured in supersonic expansions. Each rotational transition appears as a quintuplet, due to the internal rotation of the two methyl groups, which are nonequivalent in the adduct. The water moiety, linked asymmetrically to dimethoxymethane, behaves as a proton donor to one of its oxygen atoms and interferes with the internal rotation of the farther methyl group through a C...HO interaction. From the analysis of the observed splittings, the V(3) barriers to the internal rotation of the two methyl groups have been determined to be 6.83(8) and 6.19(8) kJ mol(-1). The hydrogen bond structural parameters have been determined, the O...HO and C...HO distances being 1.93(1) and 2.78(4) A, respectively.     

Noncovalent interactions in the gas phase: the anisole-phenol complex

The present paper reports on an integrated spectroscopic study of the anisole-phenol complex in a molecular beam environment. Combining REMPI and HR-LIF spectroscopy experimental data with density functional computations (TD-M05-2X/M05-2X//N07D) and first principle spectra simulations, it was possible to locate the band origin of the S(1) ← S(0) electronic transition and determine the equilibrium structure of the complex, both in the S(0) and S(1) electronic states. Experimental and computational evidence indicates that the observed band origin is due to an electronic transition localized on the phenol frame, while it was not possible to localize experimentally another band origin due to the electronic transition localized on the anisole molecule. The observed structure of the complex is stabilized by a hydrogen bond between the phenol, acting as a proton donor, and the anisole molecule, acting as an acceptor through the lone pairs of the oxygen atom. A secondary interaction involving the hydrogen atoms of the anisole methyl group and the π electron system of the phenol molecule stabilizes the complex in a nonplanar configuration. Additional insights about the landscapes of the potential energy surfaces governing the ground and first excited electronic states of the anisole-phenol complex, with the issuing implications on the system photodynamic, can be extracted from the combined experimental and computational studies.     

Noncovalent interactions: defining cooperativity. Ligand binding aided by reduced dynamic behavior of receptors. Binding of bacterial cell wall analogues to ristocetin A

Changes in the relative populations of the monomer and asymmetric dimer forms of ristocetin A, upon binding of two molecules of ligand, suggest that ligand binding is negatively cooperative with respect to dimerization. However, strong hydrogen bonds formed in the binding sites of the ligands are reinforced in the dimer relative to the monomer, and the barrier to dissociation of the dimer is increased upon binding of the ligands. It is concluded that the interactions which are common in the binding of both ligands are made with positive cooperativity with respect to those involved in dimerization. The conclusions are relevant to the binding of ligands to proteins, where ligand binding energy can be derived from stabilization of the protein in its ligand-bound form.     

Free enthalpies of replacing water molecules in protein binding pockets

Water molecules in the binding pocket of a protein and their role in ligand binding have increasingly raised interest in recent years. Displacement of such water molecules by ligand atoms can be either favourable or unfavourable for ligand binding depending on the change in free enthalpy. In this study, we investigate the displacement of water molecules by an apolar probe in the binding pocket of two proteins, cyclin-dependent kinase 2 and tRNA-guanine transglycosylase, using the method of enveloping distribution sampling (EDS) to obtain free enthalpy differences. In both cases, a ligand core is placed inside the respective pocket and the remaining water molecules are converted to apolar probes, both individually and in pairs. The free enthalpy difference between a water molecule and a CH₃ group at the same location in the pocket in comparison to their presence in bulk solution calculated from EDS molecular dynamics simulations corresponds to the binding free enthalpy of CH₃ at this location. From the free enthalpy difference and the enthalpy difference, the entropic contribution of the displacement can be obtained too. The overlay of the resulting occupancy volumes of the water molecules with crystal structures of analogous ligands shows qualitative correlation between experimentally measured inhibition constants and the calculated free enthalpy differences. Thus, such an EDS analysis of the water molecules in the binding pocket may give valuable insight for potency optimization in drug design.     

Noncovalent interactions in inorganic supramolecular chemistry based in heavy metals. Quantum chemistry point of view

Complexity is a concept that is being considered in chemistry as it has shown potential to reveal interesting phenomena. Thus, it is possible to study chemical phenomena in a new approach called systems chemistry. The systems chemistry has an organization and function, which are regulated by the interactions among its components. At the simplest level, noncovalent interactions between molecules can lead to the emergence of large structures. Consequently, it is possible to go from the molecular to the supramolecular systems chemistry, which aims to develop chemical systems highly complex through intra- and intermolecular forces. Proper use of the interactions previously mentioned allow a glimpse of supramolecular system chemistry in many tasks such as structural properties reflecting certain behaviors in the chemistry of materials, for example, electrical and optical, processes of molecular recognition and among others. In the last time, within this area, inorganic supramolecular systems chemistry has been developed. Those systems have a structural orientation which is defined by certain forces that predominate in the associations among molecules. It is possible to recognize these forces as hydrogen bonding, π-π stacking, halogen bonding, electrostatic, hydrophobic, charge transfer, metal coordination, and metallophilic interactions. The presence of these forces in supramolecular system yields certain properties such as light absorption and luminescence. The quantum theoretical modeling plays an important role in the designing of the supramolecular system. The goal is to apply supramolecular principles in order to understand the associated forces in many inorganic molecules that include heavy metals for instance gold, platinum, and mercury. Relevant systems will be studied in detail, considering functional aspects such as enhanced coordination of functionalized molecular self-assembly, electronic and optoelectronic properties.     

Pt(II) uptake by dendrimer outer pockets: 1. Solventless ligand exchange reaction

Density functional theory is used to elucidate molecular-level details of the complexation of Pt(II) metal compounds with PAMAM dendrimers. Particular attention is given to the ligand exchange reaction (LER). Binding of Pt(II) complexes to one dendrimer atom site (monodentate binding) is found to be thermodynamically feasible. Tertiary amine nitrogen (N3) is found to be the most favorable binding site in agreement with previous experimental work. Comparing the binding of Pt(II) species to atom sites in simple molecules with those to similar sites in dendrimer outer pockets allowed us to assess the impact of dendrimer branches on the binding. The impact of branches is manifested in more complex reaction profiles for complexation of Pt(II) species, because of the numerous ways in which a single molecule could be hosted by an outer dendrimer pocket. It is found that branches slightly improve the binding strength to all sites, particularly to N3. However, they could also be responsible for the increase of the activation energy for direct LER of PtCl(4)(2-) and PtCl(3)(H(2)O)- at the N3 site. Considering the thermodynamics of both complexation steps, namely noncovalent binding (NCB) and LER, it is found that to have a PtCl(3)(-) moiety bound to N3, as a result of NCB + LER operating on PtCl(4)(2-), is more likely than to have any other ion hosted in the outer pockets. However, the activation energy for direct LER of PtCl(4)(2-) at the N3 site is found to be the largest among all Pt(II) metal complexes and even larger than the barrier to its own aquation yielding PtCl(3)(H(2)O)(-).     

Noncovalent binding between fullerenes and protonated porphyrins in the gas phase

Noncovalent interactions between protonated porphyrin and fullerenes (C?? and C??) were studied with five different meso-substituted porphyrins in the gas phase. The protonated porphyrin-fullerene complexes were generated by electrospray ionization of the porphyrin-fullerene mixture in 3:1 dichloromethane/methanol containing formic acid. All singly protonated porphyrins formed the 1:1 complexes, whereas porphyrins doubly protonated on the porphine center yielded no complexes. The complex ion was mass-selected and then characterized by collision-induced dissociation with Xe. Collisional activation exclusively led to a loss of neutral fullerene, indicating noncovalent binding of fullerene to protonated porphyrin. In addition, the dissociation yield was measured as a function of collision energy, and the energy inducing 50% dissociation was determined as a measure of binding energy. Experimental results show that C?? binds to the protonated porphyrins more strongly than C??, and electron-donating substituents at the meso positions increase the fullerene binding energy, whereas electron-withdrawing substituents decrease it. To gain insight into π-π interactions between protonated porphyrin and fullerene, we calculated the proton affinity and HOMO and LUMO energies of porphyrin using Hartree-Fock and configuration interaction singles theory and obtained the binding energy of the protonated porphyrin-fullerene complex using density functional theory. Theory suggests that the protonated porphyrin-fullerene complex is stabilized by π-π interactions where the protonated porphyrin accepts π-electrons from fullerene, and porphyrins carrying bulky substituents prefer the end-on binding of C?? due to the steric hindrance, whereas those carrying less-bulky substituents favor the side-on binding of C??.     

Noncovalent immobilized artificial membrane chromatography, an improved method for describing peptide-lipid bilayer interactions.

A promising approach in assessing hydrophobic peptide-membrane interactions is the use of reversed-phase high-performance liquid chromatography. The present study describes the preparation and properties of a noncovalent immobilized artificial membrane (noncovalent IAM) stationary phase. The noncovalent IAM phase was prepared by coating the C18 chains of a reversed-phase HPLC column with the phospholipid ditetradecanoyl-sn-glycero-3-phosphocholine. Lipid coating was achieved by pumping a lipid solution in water-2-propanol through the column. The formation of a bilayer-like structure on the chromatographic surface was confirmed by calculating the phospholipid surface density of the stationary phase. The surface density was determined to be approximately 1.95 mumol m-2, which is close to that of lipid vesicles. The coating was found to be stable in chromatographic elution systems containing less than 35% of acetonitrile. Employing this new technique, we determined interaction parameters of a set of helical antibacterial magainin-2-amide peptides with pairwise substitutions of adjacent amino acids by their D-enatiomers. The results demonstrate that the chromatographic retention behavior of peptides on noncovalent IAM stationary phase shows an excellent correlation with lipid affinities to phospholipid vesicles.     

Noncovalent interactions in paired DNA nucleobases investigated by terahertz spectroscopy and solid-state density functional theory

Cocrystallized adenine and thymine derivatives, along with the pure monomeric crystals, were investigated by terahertz spectroscopy and solid-state density functional theory (DFT). The methylated nucleobase derivatives crystallize in planar hydrogen-bonded adenine-thymine pairs similar to the manner found in DNA. The spectra obtained for 1-methylthymine, 9-methyladenine, and the 1:1 cocrystal in the range of 10-100 cm(-1) clearly demonstrate that absorptions in this spectral range originate from the uniquely ordered assembly and the intermolecular interactions found in each individual crystal system. The quality of spectral reproduction for the DFT simulations of each system was clearly improved by the inclusion of an empirical correction term for London-type dispersion forces to the calculations. Notably, it was found that these weak dispersion forces in the adenine-thymine cocrystal were necessary to produce a properly converged crystal structure and meaningful simulation of the terahertz vibrational spectrum.     

Noncovalent interactions in supramolecular complexes: a study on corannulene and the double concave buckycatcher

Stimulated by the recent observation of pi-pi interactions between C60 and corannulene subunits in a molecular tweezer arrangement (J Am Chem Soc 2007, 129, 3842), a density functional theory study was performed to analyze the electronic structure and properties of various noncovalent corannulene complexes. The theoretical approach is first applied to corannulene complexes with a series of benchmark molecules (CH4, NH3, and H2O) using several new-generation density functionals. The performance of nine density functionals, illustrated by computing binding energies of the corannulene complexes, demonstrates that Zhao and Truhlar's MPWB1K and M05-2X functionals provide energies similar to that obtained at the SCS-MP2 level. In contrast, most of the other popular density functionals fail to describe this noncovalent interaction or yield purely repulsive interactions. Further investigations with the M05-2X functional show that the binding energy of C60 with corannulene subunits in the relaxed molecular receptor clip geometry is -20.67 kcal/mol. The results of this calculation further support the experimental interpretation of pure pi-pi interactions between a convex fullerene and the concave surfaces of two corannulene subunits.     

Noncovalent interactions of pentafluorobenzoate in the Zn(II) and Cd(II) complexes

[Zn(Phen)2(Pfbz)(H2O)](Pfbz)(H2O)2 (I) and 2[Cd(Phen)2(Pfbz)(ONO2)][Cd(Phen)2(ONO2)2] (II) (Phen-1,10-phtnanthroline) containing the fluorine type ligand, pentafluorobenzoate (Pfbz) have been synthesized. Elemental analysis, IR spectra, and X-ray crystal structure analysis were carried out to determine the compositions and crystal structures of the two compounds. The crystal packing exhibits intricate intermolecular π-π stacking interactions and various hydrogen bonds. The C-H···F-C interactions and weak F···F interactions play important roles in the formation of the supramolecular network. Emission properties of I and II are also investigated. The text was submitted by the authors in English.     

Quantum mechanical studies of residue-specific hydrophobic interactions in p53-MDM2 binding

Quantum chemistry calculations at the levels of MP2/cc-pVDZ and MP2/cc-PVTZ have been carried out to study residue-specific interactions at the hydrophobic p53-MDM2 binding interface. The result of the calculation, based on structures from nanosecond molecular dynamics simulation, revealed that (19)Phe, (22)Leu, and (23)Trp of p53 have the strongest binding interaction with MDM2 followed by (26)Leu and (27)Pro. The specific residues of MDM2 that have dominant binding interactions with p53 are specifically identified to be (51)Lys, (54)Leu, (62)Met, (67)Tyr, (72)Gln, (94)Lys, (96)His, and (100)Tyr. The p53-MDM2 binding interaction is dominated by van der Waals interaction and to a lesser degree by electrostatic interaction. The MP2 results are in generally good agreement with those from the force field calculation while the DFT/B3LYP calculation failed to give attractive interaction energies for certain residue-residue interactions due to the lack of dispersion energy.