DOSY NMR Spectroscopy Research Articles

Stability Evaluation and Degradation Studies of DAC® Hyaluronic-Polylactide Based Hydrogel by DOSY NMR Spectroscopy.

The stability and the degradation of polymers in physiological conditions are very important issues in biomedical applications. The copolymer of hyaluronic acid and poly-D,L-lactic acid (made available in a product called DAC®) produces a hydrogel which retains the hydrophobic character of the poly-D,L-lactide sidechains and the hydrophilic character of a hyaluronic acid backbone. This hydrogel is a suitable device for the coating of orthopedic implants with structured surfaces. In fact, this gel creates a temporary barrier to bacterial adhesion by inhibiting colonization, thus preventing the formation of the biofilm and the onset of an infection. Reabsorbed in about 72 h after the implant, this hydrogel does not hinder bone growth processes. In the need to assess stability and degradation of both the hyaluronan backbone and of the polylactic chains along time and temperature, we identified NMR spectroscopy as a privileged technique for the characterization of the released species, and we applied diffusion-ordered NMR spectroscopy (DOSY-NMR) for the investigation of molecular weight dispersion. Our diffusion studies of DAC® in physiological conditions provided a full understanding of the product degradation by overcoming the limitations observed in applying classical chromatography approaches by gel permeation UV.

MeSi(CH2 SnRO)3 (R=Ph, Me3 SiCH2 ): Building Blocks for Triangular-Shaped Diorganotin Oxide Macrocycles.

The syntheses of the novel silicon‐bridged tris(tetraorganotin) compounds MeSi(CH2SnPh2R)3 (2, R=Ph; 5, R=Me3SiCH2) and their halogen‐substituted derivatives MeSi(CH2SnPh(3−n)In)3 (3, n=1; 4, n=2) and MeSi(CH2SnI2R)3 (6, R=Me3SiCH2) are reported. The reaction of compound 4 with di‐t‐butyltin oxide (t‐Bu2SnO)3 gives the oktokaideka‐nuclear (18‐nuclear) molecular diorganotin oxide [MeSi(CH2SnPhO)3]6 (7) while the reaction of 6 with sodium hydroxide, NaOH, provides the trikonta‐nuclear (30‐nuclear) molecular diorganotin oxide [MeSi(CH2SnRO)3]10 (8, R=Me3SiCH2). Both 7 and 8 show belt‐like ladder‐type macrocyclic structures and are by far the biggest molecular diorganotin oxides reported to date. The compounds have been characterized by elemental analyses, electrospray mass spectrometry (ESI‐MS), NMR spectroscopy, 1H DOSY NMR spectroscopy (7), IR spectroscopy (7, 8), and single‐crystal X‐ray diffraction analysis (2, 7, 8).

Application of 1H DOSY NMR in Measurement of Polystyrene Molecular Weights

In this work, we studied the applicability of diffusion ordered nuclear magnetic resonance spectroscopy (DOSY NMR) as an alternative method in determination of polystyrene molecular weight. DOSY NMR spectroscopy allows measuring the diffusion coefficient of molecule which directly depend on hydrodynamic radius and so on, average molar mass in weight (Mw). By using commercial polystyrene (PS) standards, an external calibration curve was established. Based on the excellent linear correlation between diffusion coefficient (logD) and molecular weight (logM), the molecular weight of polystyrene can be predicted using the following equation . The validation was done by comparing with the Mw value obtained by gel permeation chromatography within less than 5% deviation. From the diffusion coefficient, some property of polystyrene in solution, such as Flory coefficient and polymer-solvent interaction, were also studied. The Flory coefficient confirmed that chloroform is a good solvent for PS.

Monohydride-Dichloro Rhodium(III) Complexes with Chiral Diphosphine Ligands as Catalysts for Asymmetric Hydrogenation of Olefinic Substrates.

We report full details of the synthesis and characterization of monohydride-dichloro rhodium(III) complexes bearing chiral diphosphine ligands, such as (S)-BINAP, (S)-DM-SEGPHOS, and (S)-DTBM-SEGPHOS, producing cationic triply chloride bridged dinuclear rhodium(III) complexes (1 a: (S)-BINAP; 1 b: (S)-DM-SEGPHOS) and a neutral mononuclear monohydride-dichloro rhodium(III) complex (1 c: (S)-DTBM-SEGPHOS) in high yield and high purity. Their solid state structure and solution behavior were determined by crystallographic studies as well as full spectral data, including DOSY NMR spectroscopy. Among these three complexes, 1 c has a rigid pocket surrounded by two chloride atoms bound to the rhodium atom together with one tBu group of (S)-DTBM-SEGPHOS for fitting to simple olefins without any coordinating functional groups. Complex 1 c exhibited superior catalytic activity and enantioselectivity for asymmetric hydrogenation of exo-olefins and olefinic substrates. The catalytic activity of 1 c was compared with that of well-demonstrated dihydride species derived in situ from rhodium(I) precursors such as [Rh(cod)Cl]2 and [Rh(cod)2 ]+ [BF4 ]- upon mixing with (S)-DTBM-SEGPHOS under dihydrogen.

A Reduced‐Symmetry Heterobimetallic [PdPtL4]4+ Cage: Assembly, Guest Binding, and Stimulus‐Induced Switching

AbstractA strategy is presented that enables the quantitative assembly of a heterobimetallic [PdPtL4]4+ cage. The presence of two different metal ions (PdII and PtII) with differing labilities enables the cage to be opened and closed selectively at one end upon treatment with suitable stimuli. Combining an inert PtII tetrapyridylaldehyde complex with a suitably substituted pyridylamine and PdII ions led to the assembly of the cage. 1H and DOSY NMR spectroscopy and ESI mass spectrometry data were consistent with the quantitative formation of the cage, and the heterobimetallic structure was confirmed using single‐crystal X‐ray crystallography. The structure of the host–guest adduct with a 2,6‐diaminoanthraquinone guest molecule was determined. Addition of N,N′‐dimethylaminopyridine (DMAP) resulted in the formation of the open‐cage [PtL4]2+ compound and [Pd(DMAP)4]2+ complex. This process could then be reversed, with the reformation of the cage, upon addition of p‐toluenesulfonic acid (TsOH).

Synthesis of an anthracene-based diguanidine and its recognition of carboxylic acids and phosphonic acids

An anthracene-based diguanidine (1) for the recognition of carboxylic acids and phosphonic acids has been designed and synthesized. The diguanidine 1 forms 1:1 complexes with the dicarboxylic acids and diphosphonic acids in a DMSO solution, and the formation of the 1:1 complexes was determined by DOSY NMR spectroscopy. For the recognition of methylphosphonic acid (monophosphonic acid), the formation of the 1:2 complex was also determined. The diguanidine 1 shows a characteristic yellow fluorescence in a DMSO solution that may be caused by the weak aggregation of 1 which was estimated by dilution fluorescence studies. However, after the addition of the dicarboxylic acids (30 equiv.), the yellow fluorescence of 1 disappeared (turned off the fluorescence). On the other hand, after the addition of diphosphonic acids (1 equiv.) and methylphosphonic acid (2 equiv.), the yellow emission turned to purple. These fluorescence characteristics of the diguanidine 1 are also applicable for the detection of carboxylic acids and phosphonic acids.

Heavier Alkaline-Earth Catalyzed Dehydrocoupling of Silanes and Alcohols for the Synthesis of Metallo-Polysilylethers.

The dehydrocoupling of silanes and alcohols mediated by heavier alkaline-earth catalysts, [Ae{N(SiMe3 )2 }2 ⋅(THF)2 ] (I-III) and [Ae{CH(SiMe3 )2 }2 ⋅(THF)2 ], (IV-VI) (Ae=Ca, Sr, Ba) is described. Primary, secondary, and tertiary alcohols were coupled to phenylsilane or diphenylsilane, whereas tertiary silanes are less tolerant towards bulky substrates. Some control over reaction selectivity towards mono-, di-, or tri-substituted silylether products was achieved through alteration of reaction stoichiometry, conditions, and catalyst. The ferrocenyl silylether, FeCp(C5 H4 SiPh(OBn)2 ) (2), was prepared and fully characterized from the ferrocenylsilane, FeCp(C5 H4 SiPhH2 ) (1), and benzyl alcohol using barium catalysis. Stoichiometric experiments suggested a reaction manifold involving the formation of Ae-alkoxide and hydride species, and a series of dimeric Ae-alkoxides [(Ph3 CO)Ae(μ2 -OCPh3 )Ae(THF)] (3 a-c, Ae=Ca, Sr, Ba) were isolated and fully characterized. Mechanistic experiments suggested a complex reaction mechanism involving dimeric or polynuclear active species, whose kinetics are highly dependent on variables such as the identity and concentration of the precatalyst, silane, and alcohol. Turnover frequencies increase on descending Group 2 of the periodic table, with the barium precatalyst III displaying an apparent first-order dependence in both silane and alcohol, and an optimum catalyst loading of 3 mol % Ba, above which activity decreases. With precatalyst III in THF, ferrocene-containing poly- and oligosilylethers with ferrocene pendent to- (P1-P4) or as a constituent (P5, P6) of the main polymer chain were prepared from 1 or Fe(C5 H4 SiPhH2 )2 (4) with diols 1,4-(HOCH2 )2 -(C6 H4 ) and 1,4-(CH(CH3 )OH)2 -(C6 H4 ), respectively. The resultant materials were characterized by NMR spectroscopy, gel permeation chromatography (GPC) and DOSY NMR spectroscopy, with estimated molecular weights in excess of 20,000 Da for P1 and P4. The iron centers display reversible redox behavior and thermal analysis showed P1 and P5 to be promising precursors to magnetic ceramic materials.

Isolation and characterization of a lithiated pyridine - aggregation in the solid state and in solution.

Pyridyllithiums are ubiquitous intermediates used for the electrophilic functionalization of pyridines. In this work, the isolation of a pyridyllithium is reported. Single crystal XRD revealed a dimer in the solid state. In THF solution it was identified as a monomer using DOSY NMR spectroscopy. Calculations showed that the pyridyllithium is a very electron rich pyridine superbase, which may account for its high reactivity.

Complexation of chiral amines by resorcin[4]arene sulfonic acids in polar media - circular dichroism and diffusion studies of chirality transfer and solvent dependence.

Directional self‐assembly of conformationally well-defined complexes in polar environment is still a major challenge in supramolecular chemistry. In the present study we demonstrate that resorcin[4]arene sulfonic acid (RSA) interacts with chiral amines (amino acid derivatives and aminocavitands) to form inclusion complexes and capsules based on electrostatic interactions. The complexes were characterized by circular dichroism and DOSY NMR spectroscopy. Chirality transfer from amines onto a resorcinarene skeleton was manifested by the appearance of signals in CD spectra and diastereotopic splitting in NMR spectra. The complexes proved to be thermodynamically stable in methanol, but DMSO and methanol/water mixtures were found to be highly disintegrative for these complexes. This result is quite non-intuitive and worth attention in the context of formation of supramolecular complexes in polar environment, for which DMSO is most often a first-choice solvent.

Zirconium-Nitrogen Intermolecular Frustrated Lewis Pairs.

A series of intermolecular transition metal frustrated Lewis pairs (FLPs) based on zirconocene alkoxide complexes ([Cp2Zr(OMes)]+ 1 or ([Cp*2Zr(OMes)]+ 2) with nitrogen Lewis bases (NEt3, NEtiPr2, pyridine, 2-methylpyridine, 2,6-lutidine) are reported. The interaction between Zr and N depends on the specific derivatives used, in general more sterically encumbered pairs leading to a more frustrated interaction; however, DOSY NMR spectroscopy reveals these interactions to be dynamic in nature. The pairs undergo typical FLP-type reactivity with D2, CO2, THF, and PhCCD. The catalytic dehydrocoupling of Me2NH·BH3 is also reported. Comparisons can be made with previous work employing phosphines as Lewis bases suggesting that hard-hard or hard-soft acid-base considerations are of little importance compared to the more prominent roles of steric bulk and basicity.

Study on the molecular stability, solubility, and diffusibility of guaiazulene included in β- and γ-cyclodextrin

A natural essential oil component, guaiazulene (1,4-dimethyl-7-isopropylazulene, GAZ) has a low melting point of 30–33 °C, is oily at room temperature, is poorly soluble in water (0.663 μg/mL: 25 °C), and is difficult to handle. Therefore, the current study prepared a solid dispersion using β-cyclodextrin (βCD) and γ-cyclodextrin (γCD), and the physicochemical properties, solubility, and diffusibility of those dispersions were investigated. A physical mixture (PM) and a ground mixture (GM) were prepared using GAZ, βCD, and γCD. Physicochemical properties were evaluated using differential scanning calorimetry (DSC), X-ray diffraction (PXRD), near-infrared (NIR) absorption spectroscopy, and 1H-1H NOESY NMR (D2O) spectroscopy. In addition, solubility testing was conducted and DOSY NMR spectroscopy was performed. Evaluation of the solid state of the dispersions indicated that a GM of GAZ and βCD and a GM of GAZ and γCD formed a complex at a molar ratio of 1/1, suggesting intermolecular interaction between GAZ and CD. In addition, the GM of GAZ and βCD and the GM of GAZ and γCD had improved solubility compared to that of GAZ alone. Differences in solubility were thought to be affected by the physicochemical properties of CD, stability constants, and diffusibility. Inclusion complexes of GAZ and βCD and γCD resulted in improved thermal stability and solubility.

Mono- and Hexanuclear Zinc Halide Complexes with Soft Thiopyridazine Based Scorpionate Ligands

Scorpionate ligands with three soft sulfur donor sites have become very important in coordination chemistry. Despite its ability to form highly electrophilic species, electron-deficient thiopyridazines have rarely been used, whereas the chemistry of electron-rich thioheterocycles has been explored rather intensively. Here, the unusual chemical behavior of a thiopyridazine (6-tert-butylpyridazine-3-thione, HtBuPn) based scorpionate ligand towards zinc is reported. Thus, the reaction of zinc halides with tris(6-tert-butyl-3-thiopyridazinyl)borate Na[TntBu] leads to the formation of discrete torus-shaped hexameric zinc complexes [TntBuZnX]6 (X = Br, I) with uncommonly long zinc halide bonds. In contrast, reaction of the sterically more demanding ligand K[TnMe,tBu] leads to decomposition, forming Zn(HPnMe,tBu)2X2 (X = Br, I). The latter can be prepared independently by reaction of the respective zinc halides and two equiv of HPnMe,tBu. The bromide compound was used as precursor which further reacts with K[TnMe,tBu] forming the mononuclear complex [TnMe,tBu]ZnBr(HPnMe,tBu). The molecular structures of all compounds were elucidated by single-crystal X-ray diffraction analysis. Characterization in solution was performed by means of 1H, 13C and DOSY NMR spectroscopy which revealed the hexameric constitution of [TntBuZnBr]6 to be predominant. In contrast, [TnMe,tBu]ZnBr(HPnMe,tBu) was found to be dynamic in solution.

Self-Assembly and Ordering of Peptide-Based Cavitands in Water and DMSO: The Power of Hydrophobic Effects Combined with Neutral Hydrogen Bonds.

Directional self-assembly of uncharged molecules in water is a major challenge in supramolecular chemistry. Herein, it is demonstrated that peptide-based cavitands wrap around a hydrophobic core (fullerene C60 ) by a combination of the hydrophobic effect and hydrogen-bonding interactions to form highly ordered three-component complexes in water that resemble the molten-globule stage of protein folding. The complexes were characterized by DOSY NMR spectroscopy, small-angle X-ray scattering, and circular dichroism, and their structures were confirmed by X-ray crystallography. Enhancement of the CD signals by nearly one order of magnitude and increased hydrolytic stability of hydrazone bonds of the complexes relative to the nonassembled species were observed. In contrast, DMSO and DMSO/water mixtures were found to be highly disintegrative for these complexes. Interestingly, some cavitands can only be synthesized in the presence of the hydrophobic template followed by disassembly of the complexes.

Trinuclear tris(ansa-metallocene) complexes of zirconium and hafnium for olefin polymerization

New platforms for trinuclear complexes, 1,3,5-tris(fluoren-2-yl-R)benzene (Ph{2-FluRH}3; R = H (2a), 6-tBu (2b), 7-tBu (2c), Tet (2d) (Tet = 2,2,5,5-tetramethyl-tetrahydrobenzofluorene), were synthesized via an acid-catalyzed cyclotrimerization of the corresponding substituted 2-acetylfluorenes. Subsequent nucleophilic addition of the [Ph{2-FluR}3]3− trianions onto 6,6,-dimethylfulvene afforded the corresponding isopropylidene-bridged pro-ligands Ph{Me2C(2-FluRH)(C5H5)}3 (3a-d). Discrete trinuclear tris(dichloro-ansa-zirconocene and hafnocene), Ph[{Me2C(2-FluR)(C5H4)}MX2]3 (X = Cl: 4b-d-Zr, 4c,d-Hf) were prepared by salt metathesis reactions. Some zirconium complexes were further alkylated towards the corresponding tris(dialkyls) (X = Me: 5c,d-Zr; X = CH2SiMe3: 6c-Zr). The structures of these metal complexes were determined by elemental analyses, and by 1D, inverse 2D heteronuclear correlation, and DOSY NMR spectroscopy, as well as by theoretical computations. Those studies revealed the existence of two isomers, of C3 and C1 symmetry respectively, originating from the mutual orientation of the three ansa-metallocene fragments. Preliminary studies on the catalytic performances of the dichloro complexes, upon activation with MAO, in ethylene and propylene homopolymerization and ethylene/1-hexene copolymerization were carried out and compared to those of the monometallic analogues under identical conditions.

Marigold Flower-Like Assemblies of Phosphorescent Iridium-Silver Coordination Polymers.

Racemic and enantiopure phosphorescent iridium(III)-silver(I) coordination polymers are reported. The polymers rac-, Λ-, and Δ-IrAg were formed, respectively, by the assembly of the chiral iridium metalloligands rac-, Λ-, and Δ-[Ir(mesppy)2 (qpy)]PF6 (rac-, Λ- and Δ-Ir) where mesppy is 2-phenyl-4-mesitylpyridinato and qpy is 4,4':2',2'':4'',4'''-quaterpyridine, and Ag+ ions through Npy -Ag linear coordination. The polymers have been characterized in MeNO2 solution by 1 H and 1 H DOSY NMR and CD spectroscopies and in the solid-state by scanning electron microscopy (SEM). The crystal structures of the racemic polymer rac-IrAg has been obtained by X-ray diffraction. The polymers rac-, Λ-, and Δ-IrAg exhibited orange/red emission in solution, in films and as crystals, with intensities comparable to those of the corresponding iridium metalloligands rac-, Λ-, and Δ-Ir. The morphology of the enantiopure polymers in the solid-state resembles marigold flower-like nano-porous assemblies while the racemic polymer possesses an irregular morphology formation.

Replacing calcium with ammonium counterion in lignosulfonates from paper mills affects their molecular properties and bioactivity

Lignosulfonates are important by-products of the paper industry and may be transformed into different commodities. We studied the molecular properties of ammonium (LS-AM) and calcium Lignosulfonates (LS-C) and evaluated their bioactivity towards the early development of maize plantlets. The FT-IR, 13C NMR and 1H-13C-HSQC-NMR spectra showed that the two lignosulfonates varied in hydroxyl, sulfonate and phenolic content, while DOSY-NMR spectroscopy suggested a similar diffusivity. High Performance Size Exclusion Chromatography (HPSEC) was used to simulate the effects of root-exuded acids and describe the conformational dynamics of both LS substrates in acidic aqueous solutions. This technique showed that LS-C was stabilized by the divalent Ca2+ counterion, thus showing a greater conformational stability than LS-AM, whose components could not be as efficiently aggregated by the monovalent NH4+ counter-ion. The plant bioassays revealed that LS-AM enhanced the elongation of the root system, whereas LS-C significantly increased both total and shoot plant weights. We concluded that the lignosulfonate bioactivity on plant growth depended on the applied concentrations, their molecular properties and conformational stability.

Metallosupramolecular Architectures Formed with Ferrocene-Linked Bis-Bidentate Ligands: Synthesis, Structures, and Electrochemical Studies.

The self-assembly of ligands of different geometries with metal ions gives rise to metallosupramolecular architectures of differing structural types. The rotational flexibility of ferrocene allows for conformational diversity, and, as such, self-assembly processes with 1,1'-disubstituted ferrocene ligands could lead to a variety of interesting architectures. Herein, we report a small family of three bis-bidentate 1,1'-disubstituted ferrocene ligands, functionalized with either 2,2'-bipyridine or 2-pyridyl-1,2,3-triazole chelating units. The self-assembly of these ligands with the (usually) four-coordinate, diamagnetic metal ions Cu(I), Ag(I), and Pd(II) was examined using a range of techniques including 1H and DOSY NMR spectroscopies, high-resolution electrospray ionization mass spectrometry, X-ray crystallography, and density functional theory calculations. Additionally, the electrochemical properties of these redox-active metallosupramolecular assemblies were examined using cyclic voltammetry and differential pulse voltammetry. The copper(I) complexes of the 1,1'-disubstituted ferrocene ligands were found to be coordination polymers, while the silver(I) and palladium(II) complexes formed discrete [1 + 1] or [2 + 2] metallomacrocyclic architectures.

Aggregation behavior of dihexadecylviologen bistriflimide ionic liquid crystal in different solvents: influence of polarity and concentration.

Solutions of 1,1'-dihexadecyl-4,4'-bipyridinium di[bis(trifluoromethanesulfonyl)imide] salt, also known as dihexadecylviologen bistriflimide, in deuterated acetonitrile (ACN), dichloromethane (DCM) and chloroform (CDCl3), respectively, were investigated by the combination of 1H and DOSY NMR spectroscopy, DFT calculations and MD simulation to understand the influence of solvent polarity and solute concentration (10-5-10-1 M) on its aggregation behavior. We found that the polar solvent acetonitrile (ACN) does not favor ion aggregation and cluster formation. In the whole range of concentrations investigated, the system appears to be dominated by neutral ion pairs composed of one cation and two anions, possibly in fast equilibrium (on the NMR time scale) with small or slightly larger aggregates. The diffusion coefficient of the cationic species is only weakly affected by concentration. In contrast, the low-polar solvents of chloroform (CDCl3) and dichloromethane (DCM) strongly favor cluster formation above a certain concentration and the viologen diffusion coefficient in CDCl3 is much smaller and more strongly dependent on concentration than that in ACN. The information obtained from the MD simulations suggests that the aggregates have a structure similar to the isotropic liquid phase of the viologen-based ionic liquids and ionic liquid crystals. The lifetimes of such large clusters appear to be relatively long, beyond the time scale of tens of nanoseconds. Moreover, the results from the aromatic proton NMR resonances provide some insights on the dielectric constants inside the viologen aggregates.

Ring/Chain Morphology Control in Overall‐Neutral, Internally Ion‐Paired Supramolecular Polymers

The self-assembly of internally ion-paired, neutral AA/BB-type supramolecular polymers composed of complementary di-ionizable homoditopic pairs of monomers is reported. Host-to-guest double-proton transfer mediates the recognition between bis-calix[5]arenedicarboxylic acids and α,ω-diaminoalkanes to yield cyclic, doughnut-shaped assemblies with morphologies (i.e., cyclic vs. linear) that can be controlled by means of external chemical stimuli. The behavior of these intriguing aggregates, both in solution and on surfaces, has been investigated by a combination of 1 H and DOSY NMR spectroscopy, light-scattering, and atomic force microscopy.

Turn-on fluorescence sensor for mono- and di-phosphonic acid derivatives using anthracene-based diamidine and its detection of amidinium-phosphonate and amidinium formation

The fluorescence detection of di-phosphonic acid and mono-phosphonic acid derivatives using the anthracene-based diamidine 1 has been investigated. The diamidine 1 forms 1:1 and 1:2 complexes with the di-phosphonic acid and mono-phosphonic acid derivatives, respectively, and showed a blue fluorescence (λem = 432–442 nm) in a DMSO solution. The formation of amidinium-phosphonate (complex formation) and dissociated amidinum (λem = 468 nm as a broad band) were distinguished by the difference in the fluorescence wavelength, and confirmed by DOSY NMR spectroscopy and TD-DFT calculations. The formation of a 1:2 complex with diamidine 1 and methylphosphonic acid having additional intermolecular hydrogen-bonding between the methylphosphonic acids is proposed.