Noncovalent interactions between organometallic metallocene complexes and single-walled carbon nanotubes

First principles density functional pseudopotential calculations have been used to investigate the nature of interactions between single-walled carbon nanotubes (SWNTs) and intercalated transition metal metallocene complexes, M(eta-C(5)H(5))(2) (MCp(2)). Three composites, MCp(2)-graphene (d(t)=infinity), MCp(2)@(17,0) (d(t)=1.33 nm), and MCp(2)@(12,0) (d(t)=0.94 nm) (where M=Fe,Co), have been studied to probe the influence of the nanotube diameter (d(t)) on the nature and magnitude of the interactions. Theoretical results presented here demonstrate that these MCp(2)@SWNT composites are stabilized by weak pi-stacking and CH...pi interactions, and in the case of the CoCp(2)@SWNT composites there is an additional electrostatic contribution as a result of charge transfer from CoCp(2) to the nanotube. The extent of charge transfer (MCp(2)-->SWNT) can be rationalized in terms of the electronic structures of the two fragments, or more specifically, the relative positions of the metallocene highest occupied molecular orbital and the conduction band of the nanotube in the electronic structure of the composite.     

Noncovalent coatings for the separation of synthetic polypeptides by nonaqueous capillary electrophoresis

Recently, we demonstrated the possibility to extend the range of capillary electrophoresis (CE) applications to the separation of non-water-soluble synthetic polymers. This work focuses on the control of the electro-osmotic flow (EOF) and on the limitation of the solute adsorption in nonaqueous electrolytes. For these purposes, different strategies were investigated. For the initial, a viscous additive (ethylene glycol or glycerol) was used in the electrolyte in order to decrease the EOF magnitude and, possibly, to compete with solute adsorption. A second strategy was to modify, before separation, the fused-silica capillary wall by the adsorption of poly(ethylene oxide) (PEO) via hydrogen bonding. The influence of the molecular mass of the adsorbed PEO on the EOF magnitude and direction was studied in electrolytes based on methanol/acetonitrile mixtures containing ammonium ions. For PEO molecular masses above 1000 g/mol, reversed (anodic) EOF were reported in accordance with previous results obtained with PEO covalently bonded capillaries. The influence of the nature and the concentration of the background electrolyte cation on the EOF magnitude and direction were also investigated. A third strategy consisted in modifying the capillary wall by the adsorption of a cationic polyelectrolyte layer. Advantageously, this polyelectrolyte layer suppressed the adsorption of the polymer solutes onto the capillary wall. The results obtained in this work confirm the high potential and the versatility of CE for the characterization of ionizable organic polymers in nonaqueous media.     

Dynamic ordering transitions of liquid crystals driven by interfacial complexes formed between polyanions and amphiphilic polyamines

We report the design of an amphiphilic polyamine (polymer 1) based on poly(2-alkenyl azlactone) that strongly couples the formation of polyelectrolyte complexes at aqueous/liquid crystal (LC) interfaces to ordering transitions in the LC. We demonstrate that the addition of a strong anionic polyelectrolyte to aqueous solutions in contact with polymer 1-laden LC interfaces (prepared by Langmuir-Schaefer transfer of monolayers of polymer 1 onto micrometer-thick films of nematic LC) triggers ordering transitions in the LCs. We further demonstrate that changes in the ordering of the LCs (i) are driven by electrostatic interactions between the polyelectrolytes, (ii) involve multivalent interactions between the polyelectrolytes, and (iii) are triggered by reorganization of the hydrophobic side chains of amphiphilic polymer 1 upon formation of the interfacial complexes. The results presented in this paper lead us to conclude that ordering transitions in LCs can be used to provide insights into the structure and dynamics of interfacial complexes formed between polyelectrolytes.     

Noncovalent complexes between dimethyl ether and formic acid--an ab initio and matrix isolation study.

The complexes formed by noncovalent interactions between formic acid and dimethyl ether are investigated by ab initio methods and characterized by matrix isolation spectroscopy. Six complexes with binding energies between -2.26 and -7.97 kcal mol(-1) (MP2/cc-pVTZ+zero point vibrational energy+basis set superposition erros) are identified. The two strongest bound complexes are, within a range of 0.3 kcal mol(-1), isoenergetic. The binding in these six dimers can be described in terms of OH...O, C=O...H, C-O...H and CH...O interactions. Matrix isolation spectroscopy allowed to characterize the two strongest bound complexes by their infrared spectra.     

Noncovalent paramagnetic complexes: detection of halogen bonding in solution by ESR spectroscopy

Halogen-bonded complexes between aliphatic and aromatic iodoperfluorocarbons and persistent nitroxide radicals have been detected by ESR spectroscopy in solution. Quantitative data indicate that nitroxides behave as strong electron donors in halogen bonding, giving rise to interactions whose strength is close to that of strong hydrogen bonds. These results point to a novel design of supramolecular paramagnetic species.     

Noncovalent interactions between cisplatin and graphene prototypes

Cisplatin (CP) has been widely used as an anticancer drug for more than 30 years despite severe side effects due to its low bioavailability and poor specificity. For this reason, it is paramount to study and design novel nanomaterials to be used as vectors capable to effectively deliver the drug to the biological target. The CP square‐planar geometry, together with its low water solubility, suggests that it could be possibly easily adsorbed on 2D graphene nanostructures through the interaction with the related highly conjugated π‐electron system. In this work, pyrene has been first selected as the minimum approximation to the graphene plane, which allows to properly study the noncovalent interactions determining the CP adsorption. In particular, electronic structure calculations at the MP2C and DFT‐SAPT levels of theory have allowed to obtain benchmark interaction energies for some limiting configurations of the CP–pyrene complex, as well as to assess the role of the different contributions to the total interaction: it has been found that the parallel configurations of the aggregate are mainly stabilized around the minimum region by dispersion, in a similar way as for complexes bonded through π‐π interactions. Then, the benchmark interaction energies have been used to test corresponding estimations obtained within the less expensive DFT to validate an optimal exchange‐correlation functional which includes corrections to take properly into account for the dispersion contribution. Reliable DFT interaction energies have been therefore obtained for CP adsorbed on graphene prototypes of increasing size, ranging from coronene, ovalene, and up to C₁₅₀H₃₀. Finally, DFT geometry optimizations and frequency calculations have also allowed a reliable estimation of the adsorption enthalpy of CP on graphene, which is found particularly favorable (about −20 kcal/mol at 298 K and 1 bar) being twice that estimated for the corresponding benzene adsorption. © 2017 Wiley Periodicals, Inc.     

Site-specific DNA photocleavage by rhodium intercalators analyzed by MALDI-TOF mass spectrometry

The DNA photocleavage reaction of mismatch-selective Rh complexes has been analyzed by MALDI-TOF mass spectrometry as well as gel electrophoresis analysis of radioactively tagged oligonucleotides. Analogous results are obtained with these two techniques showing site-specific cleavage neighboring the mismatch to yield primarily 5'- and 3'-phosphate termini. Additional intermediates and products are observed, however, using MALDI-TOF analysis. MALDI-TOF mass spectrometry is seen to be particularly powerful in the analysis of DNA cleavage by site-specific molecules. The method requires no radioactive labeling, only little material, and analysis can be accomplished within minutes. Moreover, this mass spectral analysis of DNA cleavage yields direct information regarding products rather than simply the base pair site of cleavage.     

Noncovalent interactions between modified cytosine and guanine DNA base pair mimics investigated by terahertz spectroscopy and solid-state density functional theory

Modified cytosine and guanine nucleobases cocrystallize in a hydrogen bonding configuration similar to that observed in native DNA. The noncovalent interactions binding these base pairs in the crystalline solid were investigated using terahertz (THz) spectroscopy and solid-state density functional theory (DFT). While stronger hydrogen bonding interactions are responsible for the general molecular orientations in the crystalline state, it is the weaker dipole-dipole and dispersion forces that determine the overall packing arrangement. The inclusion of dispersion interactions in the DFT calculations was found to be necessary to accurately simulate the unit cell structure and THz vibrational spectrum. Using properly modeled intermolecular potentials, the lattice vibrational motions of the cytosine and guanine derivatives were calculated. The vibrational characters of the modes exhibited by the DNA base pair mimic in the THz region were primarily rotational motions and are indicative of the energies and the nature of vibrations that would likely be observed between similar base pairs in DNA molecules.     

Noncovalent synthesis in aqueous solution and spectroscopic characterization of multi-porphyrin complexes

The interactions of the tetracationic meso-tetrakis(N-methyl-4-pyridyl)porphyrin (H(2)TMPyP) and its metallo derivatives (MTMPyP) (where M=copper(II), zinc(II), and gold(III) with the octa-anionic form (at neutral pH) of 5,11,17,23-tetrasulfonato-25,26,27,28-tetrakis(hydroxycarbonylmethoxy)calix[4]arene (C(4)TsTc) lead to a series of complex species whose stoichiometry and porphyrin sequence can be easily tuned. Crystallographic, spectroscopic, and diffusion NMR studies converge towards a common picture in which a central 1:4 porphyrin/calixarene unit serves as a template for the formation of more complex species. These species arise by successive, stepwise addition of single porphyrin molecules above and below the plane of the 1:4 central core to ultimately give a 7:4 complex. Noticeably, the stoichiometry of the various complex species corresponds to the actual concentration ratio of porphyrins and calixarenes in solution allowing the stoichiometry of these species to be easily tuned. This behavior and the remarkable stability of these species allow homo-porphyrin and hetero-(metallo)porphyrin species to be formed with control of not only the stoichiometry but also the sequence of the porphyrin array. The flexibility and ease of this approach permit, in principle, the design and synthesis of porphyrin arrays for predetermined purposes. For example, we have shown that it is very easy to design and obtain mixed porphyrin species in which a foreseen photoinduced electron-transfer is indeed observed.     

Noncovalent trapping and stabilization of dinuclear ruthenium complexes within a coordination cage

A dinuclear ruthenium complex, [(η(5)-indenyl)Ru(CO)(2)](2), was noncovalently enclathrated within a self-assembled coordination cage. In the cavity, rapid cis-trans isomerization and ligand exchange between the terminal and bridging carbonyls were suppressed, and only the carbonyl-bridged cis configuration was observed by X-ray crystallographic analysis.     

Characterization of specific noncovalent complexes between guanidinium derivatives and single-stranded DNA by MALDI

Noncovalently bound complexes between highly basic sites of 12 guanidinium compounds and single-stranded DNA were studied using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. 6-Aza-2-thiothymine (ATT) was used as the matrix in the presence of ammonium citrate, and spectra were recorded in the positive ion mode. Detailed control experiments confirmed unambiguously the high selectivity and specificity of the guanidinium moiety for phosphate groups of DNA. The results verify the binding stoichiometry and show preferential binding of hydrophobic binders (pyrene and anthracene guanidinium derivatives) to all sequences examined. In addition, we demonstrate that electrostatic noncovalent interactions are strengthened with phosphorothioate analogs of DNA. These results clearly highlight the structure-directing role of the self-assembling organic species and strongly emphasize the significance of concentration, hydrophobicity, hydrogen-bonding, and pi-pi interactions of the artificial receptor in the formation of these noncovalent complexes. Because of the ability of DNA-binding compounds to influence gene expression, and therefore cell proliferation and differentiation, the interactions described above could be important in providing a better understanding of the mechanism of action of these noncovalent genetic regulators.     

Detection of specific noncovalent interaction of peptide with DNA by MALDI-TOF

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry was used to obtain spectra of peptide-DNA complexes formed by basic domain (BD15) of c-Fos protein and DNA AP-1 site (5'-TGAGTCA-3'). The noncovalent interaction between single stranded DNA and BD15 was observed and confirmed to be an ionic one between the negatively charged sugar-phosphate backbone of DNA and positively charged side chains of Arg- and lys-rich peptides as demonstrated by Vertes and coworkers and Woods and coworkers. But the specific noncovalent interaction between DNA AP-1 site and the dimer of BD15 was firstly detected in this paper. Various different sequence DNAs were studied and it was found that this interaction is a sequence-specific one, and AP-1 site was essential for this interaction. This specific interaction depends on the matrix. It was only observed in the ATT matrix and not in the other two matrixes (CHCA and DHBA).     

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 Helicene Structure between Nucleic Acids and Cyanuric Acid

Cyanuric acid (CA), a triazine heterocycle, is extensively utilized for noncovalent self-assembly. The association between poly(adenine) and CA into micron-length fibers was a remarkable observation made by Sleiman and co-workers, who proposed that adenine and CA adopt a hexameric rosette configuration in analogy with previously reported structures for CA assemblies. However, recent experimental observations from the Krishnamurthy group led to a reevaluation of the hexameric rosette model, wherein they have proposed a hydrogen-bonded helicene model as an alternative. Our molecular dynamics simulations show that the hexad model is indeed unlikely and that this novel noncovalent helicene geometry, where the adenine and CA bases form an extended helical hydrogen-bond network across the system, is a more probable structural motif. The existence of noncovalent helicene compounds may have wide-ranging applications in DNA nanotechnology and helicene chemistry.     

Photocrosslinking between peptide-peptide or peptide-oligonucleotide by Ru(II)-TAP complexes

Ru(II)-TAP complexes have been shown to be very attractive compounds in the frame of developments of new anticancer drugs targeting the genetic material. This increasing interest originates from observations of covalent bond formations, triggered by photo-induced electron transfer (PET) between Ru(II)-TAP complexes and guanine bases of DNA. This photoreaction has recently been extended to the tryptophan (Trp) amino acid for future applications involving peptides. Thus, a double photo-addition of Trp residues of peptides on Ru(II) complexes is demonstrated by mass spectrometry with some structural issues. Such bi-adduct formations offer the possibility of photocrosslinking two Trp-containing biomolecules, which is investigated in this study. Thus, photocrosslinking between two complementary oligonucleotides (ODNs) derivatized by Trp-containing tripeptides is demonstrated by polyacrylamide gel electrophoresis (PAGE) in the presence of Ru(II)-TAP complexes. Both PAGE and MS indicate that such photocrosslinkings arise from two reaction pathways: either via the double addition of Trp residues on the Ru complex or from dimerization of Trp radicals. The competition between these two pathways depends on the experimental conditions. Heterobridgings between guanine bases and tryptophan residues mediated by Ru(II)-TAP complexes is also examined, opening the way to ODN-peptide photocrosslinkings.     

Affinity and nuclease activity of macrocyclic polyamines and their CuII complexes

The stability constants of Cu(II) complexes that consist of either an oxaaza macrocycle with two triamine moieties linked by dioxa chains, or two macrocyclic ligands with a polyamine chain which are connecting the 2 and 9 positions of phenanthroline, have been determined by means of potentiometric measurements. The results are compared to those reported for other ligands with a similar molecular architecture. Of the complexes that contain phenanthroline in their macrocycle, the Cu(II) ion of the complex with the smallest and most rigid macrocycle (L3) has an unsaturated coordination sphere, while in the complex with the largest macrocycle (L5) the Cu(II) ion is coordinatively almost saturated. These results are corroborated by the crystal structure of the [CuL5](ClO4)2 complex. The affinity of the ligands and the complexes towards nucleic acids was studied by measuring the changes in the melting temperature, which showed that the affinity of the macrocyclic ligands towards double-stranded DNA or RNA is generally smaller than that of their linear analogues that bear a similar charge, with a strong preference for polyA-polyU, a model for RNA. However, the complexes of two of the changed macrocyclic ligands which contain a phenanthroline unit (L4, L5) showed a distinctly larger increase in their melting temperature deltaTm with DNA (polydA-polydT), which is reversed again in favor of RNA upon metallation to the dinuclear copper complex with L5. Experiments with supercoiled plasmid DNA showed a particularly effective cleavage with a mononuclear Cu(II) complex that contains a phenanthroline unit (L6). Related ligands showed less activity towards DNA, but not so towards the biocidic bis(p-nitrophenyl)phosphate (BNPP). In both cases (with DNA and BNPP) the activity seemed to increase with decrease of coordinative saturation of the Cu(II) ion, with the exception of one particular ligand (L6). Experiments with radical scavengers in the DNA experiments showed some decrease in cleavage, which indicates the participation of redox processes.     

Evaluation of complexes of DNA duplexes and novel benzoxazoles or benzimidazoles by electrospray ionization mass spectrometry

Electrospray ionization mass spectrometry is used to compare the metal ion binding and metal-mediated DNA binding of benzoxazole (1, 2, 3, 4) and benzimidazole (5) compounds and to elucidate the putative binding modes and stoichiometries. The observed metal versus non-metal-mediated DNA binding, as well as the specificity of DNA binding, is correlated with the biological activities of the analogs. The ESI-MS spectra for the antibacterial benzoxazole and benzimidazole analogs 4 and 5 demonstrated non-specific and non-metal-mediated binding to DNA, with the appearance of DNA complexes containing multiple ligands. The anticancer analog 2 demonstrates a clear preference for metal-mediated DNA interactions, with an apparent selectivity for Ni2+ -mediated binding over the more physiologically relevant Mg2+ or Zn2+ cations. Complexation between DNA and the biologically inactive analog 1 was not observed, either in the absence or presence of metal cations.     

Noncovalent complexes of water-soluble polymers and organoplatinum compounds as potential time-release antitumor agents

The complexation of appropriate organoplatinum compounds by water-soluble polymers has the potential to provide a time-release formulation which might afford a substantial reduction in the severity of side effects associated with use of organoplatinum antitumor agents. Both poly-(N-vinylpyrrolidone)(PVP) and poly(N-vinyl-5-methyl-2-oxazolidone)(PVOM) form stable, biologically active, molecular complexes with organoplatinum compounds containing polar aromatic ligands. Platinum compounds suitable for complexation by these polymers include cis-dichloro(4-substituted o-phenylenediamine)platinum(II), 4-substitutedcatecholato(1,2-diaminocyclohexane)platinum(II), and 4-substitutedphthallato(1,2-diaminocyclohexane)-platinum(II) compounds.     

Noncovalent interactions between tetrazole and an N,N'-diethyl-substituted benzamidine

Amidines have long been known to form strong noncovalent complexes with carboxylates and phosphates. However, their interaction with tetrazoles, which are acidic heterocycles and important bioisosteric replacements for carboxylic acids in medicinal chemistry, has remained unexplored so far. The binding of a tetrazole to an N,N'-diethyl-substituted benzamidine has been studied for the first time by X-ray crystallography, solution NMR methods, and electrospray mass spectrometry. The amidinium group of model complex 3 was found to prefer an E,Z configuration in the crystal. Benzamidinium and tetrazolate groups alternate along an infinite chain of hydrogen bonds and salt bridges between the amidine-NH groups and the two tetrazole-N atoms next to the ring carbon. In solution, a 1:1 complex was evident from Job's method of continuous variation, and an association constant of 4.0 x 10(3) +/- 1.6 x 10(3) M(-)(1) (in CDCl(3)/CD(3)CN, 6:1) could be determined by (1)H NMR dilution experiments. Tetrazolate was not only found to be a weaker ligand than carboxylates but, surprisingly, the binding mode also changed with concentration in neat CDCl(3). At low concentrations, the amidine group in complex 3 adapted an E,E configuration as it does in a related carboxylic acid complex 4. With increasing concentration, the E,Z isomer starts to predominate. A free activation enthalpy DeltaG(298)() of 64 +/- 1 kJ mol(-)(1) for the E,E to E,Z isomerization was determined by line shape analysis at different magnetic fields. Binding strength was further probed in a competition experiment between a bisamidine, a carboxylate, and a tetrazolate by electrospray mass spectrometry.