Synthesis and NMR elucidation of novel pentacycloundecane‐based peptides

The synthesis and NMR elucidation of two novel pentacycloundecane (PCU)‐based peptides are reported. The PCU cage amino acids were synthesised as racemates and the incorporation of the cage amino acid with (S)‐natural amino acids produced diastereomeric peptides. The diastereomeric ‘cage’ peptides were separated using preparative HPLC and the NMR elucidation of these PCU containing peptides are reported for the first time. The ¹H and ¹³C NMR spectra showed series of overlapping signals of the cage skeleton and that of the peptide, making it extremely difficult to resolve the structure using one‐dimensional NMR techniques only. The use of two‐dimensional NMR techniques proved to be a highly effective tool in overcoming this problem. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and NMR elucidation of pentacycloundecane-derived hydroxy acid peptides as potential anti-HIV-1 agents

The synthesis and NMR elucidation of eight novel peptides incorporating the pentacycloundecane (PCU)-derived hydroxy acid are reported. The PCU cage amino acids were synthesized as racemates and the incorporation of the PCU-derived hydroxy acid with natural (S)-amino acids produced inseparable diastereomeric peptides. A series of overlapping signals from the cage and that of the peptide side chain was observed in the ¹H- and ¹³C-NMR spectra, complicating the elucidation thereof. Two-dimensional NMR techniques proved to be a very useful tool in overcoming these difficulties. These compounds are potential HIV protease inhibitors.     

Synthesis and NMR elucidation of novel pentacyclo-undecane diamine ligands

The synthesis and NMR elucidation of eight novel pentacyclo-undecane (PCU) diamine compounds are reported. These ligands are potential anti-inflammatory agents to be used against rheumatoid arthritis (RA). One-dimensional NMR techniques (¹H and ¹³C spectra) show major overlapping of methine resonances of the “cage” (PCU) thereby making it extremely difficult to assign all NMR signals. This overlapping occurs as a result of the substitutions made at the quaternary carbons (C-8/C-11) of the cage. Two-dimensional NMR techniques proved to be a useful tool in overcoming this problem.     

Floccosic Acid,a New Triterpenic Acid from Nepeta floccosa

The isolation and structure elucidation of a new triterpenic acid named floccosic acid ( 1 ) is reported on the basis of the 1D‐ and 2D‐NMR assignments. This secondary metabolite was isolated as a new constituent, along with the known triterpenoids, betulinic acid and β‐amyrin. All these compounds were purified by repeated column chromatography of the MeOH extract of Nepeta floccosa. The structure elucidation of the new compound was accomplished by the combined mass spectrometry (MS), infrared (IR) and ultraviolet (UV) absorption spectroscopy, one‐ (¹H‐ and ¹³C‐) and two‐dimensional (H? C correlations; HMBC and HSQC) NMR techniques. The known compounds were identified by comparison of their physical and spectroscopic data with those reported in the literature.     

Synthesis and properties of a novel squaraine dye modified by ferrocene

A novel squaraine dye（SQ） modified by ferrocene has been synthesized through（E）-dodecyl-2-ferrocenyl vinyl-1H-pyrrole and squaric acid.The molecular structure of SQ was characterized by ¹H NMR,¹³C NMR,MS and elemental analysis.SQ is high soluble in common solvents.The maximum absorptions of SQ in different solvents are in the range of 708-734 nm,exhibiting positive solvatochromism with increasing solvent polarity.The optical and electrical properties of SQ indicate that it is a promising electron donor material for bulk-heterojunction organic solar cell.     

Synthesis and NMR elucidation of pentacyclo-undecane diamine derivatives as potential anti-tuberculosis drugs

The complete structural elucidation of six novel pentacycloundecane (PCU) derivatives is reported. The target molecules are potential anti-tuberculosis agents. The addition of side arms to the PCU cage skeleton at position C-8/C-11 results in major overlapping of the methine resonances of the ¹H NMR spectrum. The use of 2D NMR techniques proved to be a very useful tool in overcoming the difficulties encountered in the elucidation of cage compounds using ¹H and ¹³C spectra only. All compounds reported are meso compounds thereby simplifying the complexity of the NMR spectra. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

A new method for determining positions of phenolic hydroxyl groups through silylation and application of H(Si)C triple-resonance NMR experiments

Two-dimensional triple-resonance H(Si)C NMR experiments have been applied at natural abundance to assign ¹³C NMR signals in silylated phenols. The method showing its great potential in determining positions of hydroxyl groups is widely applicable to signal assignment and structure elucidation of synthetic and natural phenolic compounds.     

Complete NMR Elucidation of Two N-Protected Trishomocubane Hydantoins and the Ethyl Ester of the Corresponding Amino Acid

In an attempt to resolve a racemic mixture of a trishomocubane hydantoin, the synthesis of a pair of novel diastereomers was obtained by protecting the racemic hydantoin with chlorocarbonic acid-(–)(R)-sec-butyl ester. An achiral i-propyl ester was first used to establish the procedure. The NMR elucidation of both the chiral and achiral N-protected hydantoins is described. Some proton and carbon NMR shifts on the cage are reversed when relative small changes on the protection group are introduced. The chiral centre on the protective group induced splitting of some carbon signals in the ¹³C spectrum on the cage skeleton, but effective separation of the diastereomers could not be obtained. In a further attempt to demonstrate the potential use of the trishomocubane amino acid in peptide synthesis, the ethyl ester of the cage amino acid was synthesised. The structures of the amino acid derivatives were elucidated with 2D NMR techniques and the assignment of the NMR data is presented.     

Structural characterization of silver dialkylphosphite salts using solid‐state 109Ag and 31P NMR spectroscopy,IR spectroscopy and DFT calculations

High‐resolution solid‐state ¹⁰⁹Ag and ³¹P NMR spectroscopy was used to investigate a series of silver dialkylphosphite salts, Ag(O)P(OR)₂ (R = CH₃, C₂H₅, C₄H₉ and C₈H₁₇), and determine whether they adopt keto, enol or dimer structures in the solid state. The silver chemical shift, CS, tensors and |J(¹⁰⁹Ag, ³¹P)| values for these salts were determined using ¹⁰⁹Ag (Ξ = 4.652%) NMR spectroscopy. The magnitudes of J(¹⁰⁹Ag, ³¹P) range from 1250 ± 10 to 1318 ± 10 Hz and are the largest reported so far. These values indicate that phosphorus is directly bonded to silver for all these salts and thus exclude the enol structure. All ³¹P NMR spectra exhibit splittings due to indirect spin–spin coupling to ¹⁰⁷Ag (I = 1/2, NA = 51.8%) and ¹⁰⁹Ag (I = 1/2, NA = 48.2%). The ¹J(¹⁰⁹Ag, ³¹P) values measured by both ¹⁰⁹Ag and ³¹P NMR spectroscopy agree within experimental error. Analysis of ³¹P NMR spectra of stationary samples for these salts allowed the determination of the phosphorus CS tensors. The absence of characteristic P?O stretching absorption bands near 1250 cm^?1 in the IR spectra for these salts exclude the simple keto tautomer. Thus, the combination of solid‐state NMR and IR results indicate that these silver dialkylphosphite salts probably have a dimer structure. Values of silver and phosphorus CS tensors as well as ¹J(¹⁰⁹Ag, ³¹P) values for a dimer model calculated using the density functional theory (DFT) method are in agreement with the experimental observations. Copyright © 2010 John Wiley & Sons, Ltd.     

Solid-state high-resolution NMR studies on spin fluctuation associated with valence tautomerism of metal–benzoquinone system: Cobalt complex in the stable and meta-stable phases

Equilibrium between low-spin [Co^III(SQ)(Cat)(N–N)] and high-spin [Co^II(SQ)₂(N–N)] redox isomers, where SQ is semiquinonate (charge: −1, spin: 1/2), Cat is catecholate (charge: −2, spin: 0) and N–N is chelating nitrogen donor ligand, respectively, is a representative valence tautomeric phenomenon. To elucidate independently the spin state of the cobalt ion and that of benzoquinone-derived ligands in the solid state, we measured ¹³C MAS NMR spectrum of 3,5-di-t-butyl-1,2-benzoquinone and ²H MAS NMR spectrum of deuterated 2,2′-bipyridine for [Co(3,5-di-t-butyl-1,2-benzoquinone)₂(2,2′-bipyridine)] · x(C₆H₅CH₃) and its deuterated analogue in a temperature range of 200–350 K. Irreversible change of an effective magnetic moment μ_eff of a virgin sample was observed around 370 K due to a partial loss of crystal solvent and a change of crystal structure, whereas the sample annealed at 390 K showed a crystal structure different from the reported one and a reversible change of μ_eff, which is ascribed to equilibrium between Co(III)-form (S = 1/2) and Co(II)-form (S = 3/2). Based on the shifts and the number of NMR peaks for the annealed sample, we concluded that (1) interconversion between redox isomers occurs faster than NMR time scale (>10⁴ s⁻¹) in the solid state, (2) intraconversion between SQ and Cat in Co(III)-form also occurs much faster than 5 × 10⁴ s⁻¹ even at 198 K and (3) electron spins on SQ ligands in Co(II)-form are quenched probably due to a strong antiferromagnetic coupling between the two SQ ligands. The enthalpy and the entropy of the interconversion were estimated to be 17 kJ/mol and 54 J/(K mol), respectively. For the virgin metastable phase, SQ and Cat were clearly distinguished by ¹³C MAS NMR spectrum. The solid-state high-resolution NMR spectrum is useful to detect independently the change of spin states of benzoquinone-derived radical and metal ion.     

NMR elucidation of some pentacycloundecane derived ligands

The complete NMR elucidation of four pentacycloundecane (PCU) derived ligands is reported. 2D NMR techniques are used to overcome the problem of major overlapping of methine signals on the cage skeleton. One of the cage ligands is chiral and the ¹³C NMR signals of the leucinol side “arms” to the cage appear to be split into two or more peaks indicating either impurities or conformational differences. Impurities were ruled out and the only logical explanation for this unusual observation appears to be conformational effects due to different positions of the two relative bulky side chains or “arms”. The rigid cage skeleton is known for through space deshielding of signals in close proximity to oxygen atoms attached to the cage skeleton. The leucinol side chains in closer proximity to the cage ether bridge would experience a larger shielding effect causing those carbon atoms to be shifted upfield with respect to the corresponding atoms in other conformations. The intrinsic chiral nature of the cage could also play a role in this case to perhaps enhance the observed effect. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

<Superscript>13</Superscript>C NMR and mass spectrometry of soil organic matter

Liquid state, high resolution ¹³C NMR spectroscopy and mass spectrometry were used to study the composition and structure of soil organic matter (SOM) using soil extracts from two long-term experiments at the Rothamsted Experimental Station. Both one- and two-dimensional NMR techniques were applied. ¹³C NMR sub-spectra of the CH _n (n=0...3) groups, obtained by the Distortionless Enhancement by Polarisation Transfer (DEPT) technique, were used for the elucidation of the qualitative and quantitative composition of humic and fulvic acids in the soils. The chemical structure of SOM was further analysed at the molecular level through Fast Atom Bombardment Mass Spectrometry (FABMS) and Gas Chromatography-Mass Spectrometry (GC/MS). Humic and fulvic extract results were not only compared to each other, but also to the solid state ¹³C NMR results for the complete soil sample.     

Direct rapid analysis of trace bioavailable soil macronutrients by chemometrics-assisted energy dispersive X-ray fluorescence and scattering spectrometry

Precision agriculture depends on the knowledge and management of soil quality (SQ), which calls for affordable, simple and rapid but accurate analysis of bioavailable soil nutrients. Conventional SQ analysis methods are tedious and expensive. We demonstrate the utility of a new chemometrics-assisted energy dispersive X-ray fluorescence and scattering (EDXRFS) spectroscopy method we have developed for direct rapid analysis of trace ‘bioavailable’ macronutrients (i.e. C, N, Na, Mg, P) in soils. The method exploits, in addition to X-ray fluorescence, the scatter peaks detected from soil pellets to develop a model for SQ analysis. Spectra were acquired from soil samples held in a Teflon holder analyzed using ¹⁰⁹Cd isotope source EDXRF spectrometer for 200 s. Chemometric techniques namely principal component analysis (PCA), partial least squares (PLS) and artificial neural networks (ANNs) were utilized for pattern recognition based on fluorescence and Compton scatter peaks regions, and to develop multivariate quantitative calibration models based on Compton scatter peak respectively. SQ analyses were realized with high CMD (R² > 0.9) and low SEP (0.01% for N and Na, 0.05% for C, 0.08% for Mg and 1.98 μg g⁻¹ for P). Comparison of predicted macronutrients with reference standards using a one-way ANOVA test showed no statistical difference at 95% confidence level. To the best of the authors’ knowledge, this is the first time that an XRF method has demonstrated utility in trace analysis of macronutrients in soil or related matrices.     

19F-Labeled Probes for Recognition-Enabled Chromatographic 19F NMR

The NMR technique is among the most powerful analytical methods for molecular structural elucidation, process monitoring, and mechanistic investigations; however, the direct analysis of complex real-world samples is often hampered by crowded NMR spectra that are difficult to interpret. The combination of fluorine chemistry and supramolecular interactions leads to a unique detection method named recognition-enabled chromatographic (REC) ¹⁹F NMR, where interactions between analytes and ¹⁹F-labeled probes are transduced into chromatogram-like ¹⁹F NMR signals of discrete chemical shifts. In this account, we summarize our endeavor to develop novel ¹⁹F-labeled probes tailored for separation-free multicomponent analysis. The strategies to achieve chiral discrimination, sensitivity enhancement, and automated analyte identification will be covered. The account will also provide a detailed discussion of the underlying principles for the design of molecular probes for REC ¹⁹F NMR where appropriate.     

13C and19F NMR study of α,β-difluorostyryl derivatives of transition metal carbonylates. A method of signal assignment based on the carbon—fluorine spin-spin coupling constants

The¹³C and¹⁹F NMR spectra ofZ- andE-isomers of β-X-substituted α,β-difluorostyrenes (X=F, Cl, CpFe(CO)₂, Re(CO)₅, Re₂(CO)₉Na) were studied. Direct and long-range (across 1–5 bonds) spin-spin coupling constants and the (¹³C−¹²C) isotope shifts in the¹⁹F NMR spectra were determined. The study of the¹³C satellites in the¹⁹F NMR spectra of substituted difluorostyrenes permitted assignment of the¹³C NMR signals of the vinylic carbon atoms. Similarly, the signals in¹⁹F NMR spectra were assigned based on coupling constants of fluorine withipso-carbon. These assignments were found to be in good agreement with the data available from the literature (X=F, Cl). The developed approach was applied to the elucidation of the structure ofZ−PhCF=CClFe(CO)₂Cp. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya. No. 8, pp. 1575–1579, August, 1998.     

Advanced solvent signal suppression for the acquisition of 1D and 2D NMR spectra of Scotch Whisky

A simple and robust solvent suppression technique that enables acquisition of high‐quality 1D ¹H nuclear magnetic resonance (NMR) spectra of alcoholic beverages on cryoprobe instruments was developed and applied to acquire NMR spectra of Scotch Whisky. The method uses 3 channels to suppress signals of water and ethanol, including those of ¹³C satellites of ethanol. It is executed in automation allowing high throughput investigations of alcoholic beverages. On the basis of the well‐established 1D nuclear Overhauser spectroscopy (NOESY) solvent suppression technique, this method suppresses the solvent at the beginning of the pulse sequence, producing pure phase signals minimally affected by the relaxation. The developed solvent suppression procedure was integrated into several homocorrelated and heterocorrelated 2D NMR experiments, including 2D correlation spectroscopy (COSY), 2D total correlation spectroscopy (TOCSY), 2D band‐selective TOCSY, 2D J‐resolved spectroscopy, 2D ¹H, ¹³C heteronuclear single‐quantum correlation spectroscopy (HSQC), 2D ¹H, ¹³C HSQC‐TOCSY, and 2D ¹H, ¹³C heteronuclear multiple‐bond correlation spectroscopy (HMBC). A 1D chemical‐shift‐selective TOCSY experiments was also modified. The wealth of information obtained by these experiments will assist in NMR structure elucidation of Scotch Whisky congeners and generally the composition of alcoholic beverages at the molecular level.     

Nepethalates A and B: Two New Phthalate Derivatives from Nepeta clarkei

The structure elucidation of two new phthalate derivatives named nepethalates A ( 1 ) and B ( 2 ) is reported. Both of these secondary metabolites were isolated from the MeOH extract of Nepeta clarkei. HR‐EI‐MS, IR and UV absorption spectrometry, and NMR experiments including COSY, HMQC, and HMBC were used for the determination of the structures and complete ¹H‐ and ¹³C‐NMR assignments.     

Direct syntheses of a series of cucurbit[n]uril-anchored polyacrylamides

Using the one-pot, direct strategy reported by Su and co-workers, we have synthesised a series of cucurbit[n]urils (Q[n], n = 5–8) and alkyl-substituted cucurbit[6]urils (SQ[6]s) anchored on polymers. Acrylamide, as a typical monomer, was used to synthesise a series of Q[n]s (n = 5–8) and SQ[6]-anchored polyacrylamides (PAMs) using a persulfate salt as initiator and oxidant. The Q[n]s (n = 5–8) and SQ[6]-anchored PAM samples have been characterised by ¹H NMR, ¹H NMR titrations of probe guests, Fourier-transform infrared and thermogravimetric analyser. The results confirmed that PAM chains had been successfully grafted on the back of the Q[n]s (n = 5–8) and SQ[6]s through an in situ radical polymerisation approach. It was further confirmed that the hydrophobic cavities of the Q[n]s on the polymers were still freely accessible. This synthetic approach may be extended to a variety of Q[n]s that are difficult to functionalise.     

Combination of DQ and ZQ Coherences for Sensitive Through‐Bond NMR Correlation Experiments in Biosolids under Ultra‐Fast MAS

A double‐zero quantum (DZQ)‐refocused INADEQUATE experiment is introduced for J‐based NMR correlations under ultra‐fast (60 kHz) magic angle spinning (MAS). The experiment records two spectra in the same dataset, a double quantum–single quantum (DQ‐SQ) and zero quantum–single quantum (ZQ‐SQ) spectrum, whereby the corresponding signals appear at different chemical shifts in ω₁. Furthermore, the spin‐state selective excitation (S³E) J‐decoupling block is incorporated in place of the second refocusing echo of the INADEQUATE scheme, providing an additional gain in sensitivity and resolution. The two sub‐spectra acquired in this way can be treated separately by a shearing transformation, producing two diagonal‐free single quantum (SQ‐SQ)‐type spectra, which are subsequently recombined to give an additional sensitivity enhancement, thus offering an improvement greater than a factor of two as compared to the original refocused INADEQUATE experiment. The combined DZQ scheme retains transverse magnetization on the initially polarized (I) spin, which typically exhibits a longer transverse dephasing time (T₂′) than its through‐bond neighbour (S). By doing so, less magnetization is lost during the refocusing periods in the sequence to give even further gains in sensitivity for the J correlations. The experiment is demonstrated for the correlation between the carbonyl (CO) and alpha (CA) carbons in a microcrystalline sample of fully protonated, [¹⁵N,¹³C]‐labelled Cu^II, Zn^II superoxide dismutase, and its efficiency is discussed with respect to other J‐based schemes.     

Structural Insights into Peptides Bound to the Surface of Silica Nanopores

The structure and surface functionalization of biologically relevant silica-based hybrid materials was investigated by 2D solid-state NMR techniques combined with dynamic nuclear polarization (DNP). This approach was applied to a model system of mesoporous silica, which was modified through in-pore grafting of small peptides by solid-phase peptide synthesis (SPPS). To prove the covalent binding of the peptides on the surface, DNP-enhanced solid-state NMR was used for the detection of ¹⁵N NMR signals in natural abundance. DNP-enhanced heterocorrelation experiments with frequency switched Lee–Goldburg homonuclear proton decoupling (¹H–¹³C and ¹H–¹⁵N CP MAS FSLG HETCOR) were performed to verify the primary structure and configuration of the synthesized peptides. ¹H FSLG spectra and ¹H-²⁹Si FSLG HETCOR correlation spectra were recorded to investigate the orientation of the amino acid residues with respect to the silica surface. The combination of these NMR techniques provides detailed insights into the structure of amino acid functionalized hybrid compounds and allows for the understanding for each synthesis step during the in-pore SPPS.