HMBC‐1,n‐ADEQUATE spectra calculated from HMBC and 1,n‐ADEQUATE spectra

Unsymmetrical and generalized indirect covariance processing methods provide a means of mathematically combining pairs of 2D NMR spectra that share a common frequency domain to facilitate the extraction of correlation information. Previous reports have focused on the combination of HSQC spectra with 1,1‐, 1,n‐, and inverted ¹J_CC 1,n‐ADEQUATE spectra to afford carbon–carbon correlation spectra that allow the extraction of direct (¹J_CC), long‐range (ⁿJ_CC, where n ≥ 2), and ¹J_CC‐edited long‐range correlation data, respectively. Covariance processing of HMBC and 1,1‐ADEQUATE spectra has also recently been reported, allowing convenient, high‐sensitivity access to ⁿJ_CC correlation data equivalent to the much lower sensitivity n,1‐ADEQUATE experiment. Furthermore, HMBC‐1,1‐ADEQUATE correlations are observed in the F₁ frequency domain at the intrinsic chemical shift of the ¹³C resonance in question rather than at the double‐quantum frequency of the pair of correlated carbons, as visualized by the n,1, and m,n‐ADEQUATE experiments, greatly simplifying data interpretation. In an extension of previous work, the covariance processing of HMBC and 1,n‐ADEQUATE spectra is now reported. The resulting HMBC‐1,n‐ADEQUATE spectrum affords long‐range carbon–carbon correlation data equivalent to the very low sensitivity m,n‐ADEQUATE experiment. In addition to the significantly higher sensitivity of the covariance calculated spectrum, correlations in the HMBC‐1,n‐ADEQUATE spectrum are again detected at the intrinsic ¹³C chemical shifts of the correlated carbons rather than at the double‐quantum frequency of the pair of correlated carbons. HMBC‐1,n‐ADEQUATE spectra can provide correlations ranging from diagonal (⁰J_CC or diagonal correlations) to ⁴J_CC under normal circumstances to as much as ⁶J_CC in rare instances. The experiment affords the potential means of establishing the structures of severely proton‐deficient molecules. Copyright © 2013 John Wiley & Sons, Ltd.     

Inversion of 1JCC correlations in 1,n‐ADEQUATE spectra

ADEQUATE experiments provide an alternative to the more commonly employed GHMBC experiment for the establishment of long‐range heteronuclear connectivities. The 1,1‐ADEQUATE experiment allows the unequivocal identification of both protonated and non‐protonated carbon resonances adjacent to a protonated carbon. The 1,n‐ADEQUATE experiment establishes correlations via an initial ¹J_CH heteronuclear transfer followed by an ⁿJ_CC out‐and‐back transfer, most typically, via three carbon–carbon bonds. Hence, the 1,n‐ADEQUATE experiment allows the equivalent of ⁴J_CH heteronuclear correlations to be probed when they are not observed in a GHMBC spectrum. Aside from the lower sensitivity of the 1,n‐ADEQUATE experiment relative to GHMBC experiments, the interpretation of the former is also complicated by the ‘leakage’ of ¹J_CC correlations into the spectrum that must be identified. A method for the inversion of ¹J_CC correlations to facilitate the interpretation of 1,n‐ADEQUATE spectra is presented that allows a single experiment to be performed to access ¹J_CC and ⁿJ_CC correlation information. Copyright © 2012 John Wiley & Sons, Ltd.     

HMBC‐1,1‐ADEQUATE via generalized indirect covariance: a high sensitivity alternative to n,1‐ADEQUATE

1,1‐ADEQUATE and the related long‐range 1,n‐ and n,1‐ADEQUATE variants were developed to provide an unequivocal means of establishing ²J_CH and the equivalent of ⁿJ_CH correlations where n = 3,4. Whereas the 1,1‐ and 1,n‐ADEQUATE experiments have two simultaneous evolution periods that refocus the chemical shift and afford net single quantum evolution for the carbon spins, the n,1‐variant has a single evolution period that leaves the carbon spin to be observed at the double quantum frequency. The n,1‐ADEQUATE experiment begins with an HMBC‐type ⁿJ_CH magnetization transfer, which leads to inherently lower sensitivity than the 1,1‐ and 1,n‐ADEQUATE experiments that begin with a ¹J_CH transfer. These attributes, in tandem, serve to render the n,1‐ADEQUATE experiment less generally applicable and more difficult to interpret than the 1,n‐ADEQUATE experiment, which can in principle afford the same structural information. Unsymmetrical and generalized indirect covariance processing methods can complement and enhance the structural information encoded in combinations of experiments e.g. HSQC‐1,1‐ or ?1,n‐ADEQUATE. Another benefit is that covariance processing methods offer the possibility of mathematically combining a higher sensitivity 2D NMR spectrum with for example 1,1‐ or 1,n‐ADEQUATE to improve access to the information content of lower sensitivity congeners. The covariance spectrum also provides a significant enhancement in the F₁ digital resolution. The combination of HMBC and 1,1‐ADEQUATE spectra is shown here using strychnine as a model compound to derive structural information inherent to an n,1‐ADEQUATE spectrum with higher sensitivity and in a more convenient to interpret single quantum presentation. Copyright © 2012 John Wiley & Sons, Ltd.     

HSQC-1,n-ADEQUATE: a new approach to long-range 13C-13C correlation by covariance processing

Long-range, two-dimensional heteronuclear shift correlation NMR methods play a pivotal role in the assembly of novel molecular structures. The well-established GHMBC method is a high-sensitivity mainstay technique, affording connectivity information via (n)J(CH) coupling pathways. Unfortunately, there is no simple way of determining the value of n and hence no way of differentiating two-bond from three- and occasionally four-bond correlations. Three-bond correlations, however, generally predominate. Recent work has shown that the unsymmetrical indirect covariance or generalized indirect covariance processing of multiplicity edited GHSQC and 1,1-ADEQUATE spectra provides high-sensitivity access to a (13)C-(13) C connectivity map in the form of an HSQC-1,1-ADEQUATE spectrum. Covariance processing of these data allows the 1,1-ADEQUATE connectivity information to be exploited with the inherent sensitivity of the GHSQC spectrum rather than the intrinsically lower sensitivity of the 1,1-ADEQUATE spectrum itself. Data acquisition times and/or sample size can be substantially reduced when covariance processing is to be employed. In an extension of that work, 1,n-ADEQUATE spectra can likewise be subjected to covariance processing to afford high-sensitivity access to the equivalent of (4)J(CH) GHMBC connectivity information. The method is illustrated using strychnine as a model compound.     

HSQC-ADEQUATE correlation: a new paradigm for establishing a molecular skeleton

Various experimental methods have been developed to unequivocally identify vicinal neighbor carbon atoms. Variants of the HMBC experiment intended for this purpose have included 2J3J-HMBC and H2BC. The 1,1-ADEQUATE experiment, in contrast, was developed to accomplish the same goal but relies on the (1) J(CC) coupling between a proton-carbon resonant pair and the adjacent neighbor carbon. Hence, 1,1-ADEQUATE can identify non-protonated adjacent neighbor carbons, whereas the 2J3J-HMBC and H2BC experiments require both neighbor carbons to be protonated to operate. Since 1,1-ADEQUATE data are normally interpreted with close reference to an HSQC spectrum of the molecule in question, we were interested in exploring the unsymmetrical indirect covariance processing of multiplicity-edited GHSQC and 1,1-ADEQUATE spectra to afford an HSQC-ADEQUATE correlation spectrum that facilitates the extraction of carbon-carbon connectivity information. The HSQC-ADEQUATE spectrum of strychnine is shown and the means by which the carbon skeleton can be conveniently traced is discussed.     

Homodecoupled 1,1‐ and 1,n‐ADEQUATE: Pivotal NMR Experiments for the Structure Revision of Cryptospirolepine

Cryptospirolepine is the most structurally complex alkaloid discovered and characterized thus far from any Cryptolepis specie. Characterization of several degradants of the original, sealed NMR sample a decade after the initial report called the validity of the originally proposed structure in question. We now report the development of improved, homodecoupled variants of the 1,1‐ and 1,n‐ADEQUATE (HD‐ADEQUATE) NMR experiments; utilization of these techniques was critical to successfully resolving long‐standing structural questions associated with crytospirolepine.     

Measurement of long‐range proton–carbon coupling constants from pure in‐phase 1D multiplets

The SELective INverse detection of carbon–proton CORrelation pulse sequence that yields a 1D spectrum of a proton directly bonded to a selected carbon resonance has been converted into a proton and carbon double‐selective variant that provides a ¹H spectrum of a selected proton that is long‐range coupled to a specific carbon resonance. The resulting 1D proton multiplet exhibits a pure absorptive in‐phase lineshape for precise measurement of specific long‐range proton–carbon coupling constants in small organic molecules at natural abundance. Copyright © 2011 John Wiley & Sons, Ltd.     

3D Heteronuclear long‐range 1H–13C scalar correlation at natural abundance: application to oligosaccharide analysis

A 3D ¹H–¹³C–¹H refocused INEPT transfer experiment is proposed in which the initial coherence transfer of ¹H longitudinal to ¹³C transverse magnetization is tuned to the long‐range ¹H, ¹³C couplings while the reverse INEPT component transfers the magnetization to the directly bonded ¹H. Integration of a constant time ¹H evolution period into the long‐range coherence transfer interval provides absorption mode signals for each dimension. A ¹³C purge component at the beginning of the sequence selects for ¹²C‐bound ¹H magnetization that is then transferred to a ¹³C‐bound hydrogen, thus strongly suppressing the diagonal signals. This experiment is expected to be of particular value for situations in which resonance overlap in the ¹³C dimension renders 2D long‐range heteronuclear correlation data ambiguous. In combination with a diagonal‐suppressed 3D ¹H–¹³C–¹H TOCSY‐HSQC experiment, complete assignment of the ring resonances of the Lewis‐b hexasaccharide was obtained on a 4.2 mM sample using a conventional 500 MHz probe (0.1% ethylbenzene signal‐to‐noise ratio of 600), suggesting its applicability to sub‐millimolar samples using cryoprobe technology. Copyright © 2002 John Wiley & Sons, Ltd.     

A new strategy to design a graphene oxide supported palladium complex as a new heterogeneous nanocatalyst and application in carbon–carbon and carbon‐heteroatom cross‐coupling reactions

The palladium nanoparticles were successfully stabilized with an average diameter of 6–7 nm through the coordination of palladium and terpyridine‐based ligands grafted on graphene oxide surface. The graphene oxide supported palladium nanoparticles were thoroughly characterized and applied as an efficient heterogeneous catalyst in carbon–carbon (Suzuki‐Miyaura, Mizoroki‐Heck coupling reactions) and carbon–heteroatom (C‐N and C‐O) bond‐forming reactions. The catalyst was simply recycled from the reaction mixture and was reused consecutive four times with small drop in catalytic activity.     

1,3‐Dichloro‐tetra‐n‐butyl‐distannoxane: a new application for catalyzing the direct substitution of 9H‐xanthen‐9‐ol at room temperature

1,3‐Dichloro‐tetra‐n‐butyl‐distannoxane was firstly used to catalyze the direct substitution of 9H‐xanthen‐9‐ol with indoles at room temperature to afford a class of 3‐(9H‐xanthen‐9‐yl)‐1H‐indole derivatives in good to excellent isolating yield. Moreover, other nucleophiles (such as diketone and pyrrole) could also proceed smoothly in this methodology. Copyright © 2012 John Wiley & Sons, Ltd.     

BASHD‐J‐resolved‐HMBC,an efficient method for measuring proton–proton and heteronuclear long‐range coupling constants

Natural products often possess various spin systems consisting of a methine group directly bonded to a methyl group (e.g. –CH_a–CH_b(CH₃)–CH_c–). The methine proton H_b splits into a broadened multiplet by coupling with several vicinal protons, rendering analysis difficult of ⁿJ_C–H with respect to H_b in the J‐resolved HMBC‐1. In purpose of the reliable and easy measurements of ⁿJ_C–H and ⁿJ_H–H in the aforesaid spin system, we have developed a new technique, named BASHD‐J‐resolved‐HMBC. This method incorporates band selective homo decoupled pulse and J‐scaling pulse into HMBC. In this method, high resolution cross peaks can be observed along the F₁ axis by J‐scaling pulse, and band selective homo decoupled pulse simplified multiplet signals. Determinations of ⁿJ_C–H and ⁿJ_H–H of multiplet signals can easily be performed using the proposed pulse sequence. Copyright © 2013 John Wiley & Sons, Ltd.     

A toolbox of HSQC experiments for small molecules at high 13C‐enrichment. Artifact‐free,fully 13C‐homodecoupled and JCC‐encoding pulse sequences

A set of modified HSQC experiments designed for the study of ¹³C‐enriched small molecules is introduced. It includes an improved sensitivity‐enhanced HSQC experiment eliminating signal artifacts because of high‐order ¹³C magnetization terms generated at high ¹³C enrichment. A broadband homonuclear ¹³C decoupling sequence based on Zangger and Sterk's method simplifies the complex ¹³C–¹³C multiplet structure in the F1 dimension of HSQC. When recording spectra at high resolution, the combination with a multiple‐site modulation of the selective pulse outperforms the constant‐time HSQC in terms of sensitivity and reliability. Finally, two pulse sequences reintroducing selected J_CC couplings with selective pulses facilitate their assignments and measurements either in the splitting of the resulting doublets or by modulation of the signal amplitude. A sample of uniformly 92% ¹³C‐enriched cholesterol is used as an example. Copyright © 2013 John Wiley & Sons, Ltd.     

Iron(II) and Nickel(II) Complexes of N‐Alkylimidazoles and 1‐Methyl‐1H‐1, 2, 4‐Triazole: X‐ray Studies,Magnetic Characterization,and DFT Calculations

Using the ligands N‐methylimidazole ( MeIm ), N‐ethylimidazole ( EtIm ), N‐propylimidazole ( PrIm ), and 1‐methyl‐1H‐1, 2, 4‐triazole ( MeTz ) three series with a total of 13 iron(II) complexes were isolated. The series comprise of the following complexes: (a) [Fe( MeIm )₆](ClO₄)₂ ( 1 ), [Fe( EtIm )₆](ClO₄)₂ ( 2 ), [Fe( PrIm )₆](ClO₄)₂( 3 ), [Fe( MeTz )₆](ClO₄)₂ ( 4 ), [Fe( MeIm )₆](MeSO₃)₂ ( 5 ), [Fe( EtIm )₆](MeSO₃)₂ ( 6 ), and [Fe( MeTz )₆](BF₄)₂ ( 10 ); (b) [Fe( MeIm )₄(MeSO₃)₂]( 7 ), [Fe( EtIm )₄(MeSO₃)₂] ( 8 ), and [Fe( PrIm )₄(MeSO₃)₂] ( 9 ); (c) [Fe( MeIm )₄(NCS)₂] ( 15 ), [Fe( EtIm )₄(NCS)₂] ( 16 ), and [Fe( MeTz )₄(NCS)₂] ( 17 ). Single crystal X‐ray diffraction studies were performed on 7 – 10 and 15 – 17 . Temperature dependent magnetic susceptibility measurements were performed on selective examples of all series, and confirmed them to be in the HS state over the range 6–300 K. DFT calculations were performed at BP86/def‐SV(P) and TPSSh/def2‐TZVPP level on all [Fe L ₆]²⁺ complex cations and the neutral complexes 7 – 9 and 15 – 17 . Additionally the four homoleptic nickel(II) complexes [Ni L ₆](ClO₄)₂ ( 11 : L = MeIm ; 12 : L = EtIm ; 13 : L = PrIm ; 14 : L = MeTz ) were synthesized and compounds 11 – 13 structurally characterized. UV/Vis/NIR spectroscopic measurements were carried out on all homoleptic iron(II) and nickel(II) complexes. The 10Dq values were determined to be in the range of 11547–11574 and 10471–10834 cm^–1 for the iron(II) and nickel(II) complexes, respectively.     

Spatial structure of heptapeptide Aβ16–22 (beta‐amyloid Aβ1–40 active fragment) in solution and in complex with a biological membrane model

The spatial structure of an active fragment of beta‐amyloid Aβ_1–40 heptapeptide Aβ_16–22 (Lys‐Leu‐Val‐Phe‐Phe‐Ala‐Glu) in aqueous buffer solution and in complex with sodium dodecyl sulfate micelles as a model membrane system was investigated by ¹H NMR spectroscopy and two‐dimensional NMR (TOCSY, HSQC‐HECADE (Heteronuclear Couplings from ASSCI‐domain experiments with E.COSY‐type crosspeaks), NOESY) spectroscopy. Complex formation was confirmed by the chemical shift changes of the heptapeptide's ¹H NMR spectra, as well as by the signs and values of the NOE effects in different environments. We compared the spatial structure of the heptapeptide in borate buffer solution and in complex with a model of the cell surface membrane. Copyright © 2012 John Wiley & Sons, Ltd.     

α‐Fe2O3 Polyhedral Nanoparticles Enclosed by Different Crystal Facets: Tunable Synthesis,Formation Mechanism Analysis,and Facets‐dependent n‐Butanol Sensing Properties

Three kinds of polyhedral α‐Fe₂O₃ nanoparticles enclosed by different facets including oblique parallel hexahedrons (op‐hexahedral NPs), cracked oblique parallel hexahedrons (cop‐hexahedral NPs), and octadecahedral nanoparticles (octadecahedral NPs), were successfully prepared by simply changing only one reaction parameter in the hydrothermal process. The structural and morphological of the products were systematically studied using various characterizations including X‐ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), revealing that the three kinds of α‐Fe₂O₃ nanoparticles were enclosed by {104}, {110}/{104}, and {102}/{012}/{104} crystal planes, respectively. The exposed facets and shape of the nanocrystals were found to be affected by the adding amount of ethylene glycol in the solvent. The gas‐sensing properties and mechanism of the α‐Fe₂O₃ samples were studied and analyzed, which indicated that the sensitivity of the three samples followed the order of octadecahedral NPs > cop‐hexahedral NPs > op‐hexahedral NPs due to the combined effects of specific surface area and oxygen defects in the nanocrystals.     

Probing long‐range spin–spin coupling constants in 2‐halo‐substituted cyclohexanones and cyclohexanethiones: The role of solvent and stereoelectronic effects

Earlier studies with 2‐bromocyclohexanone demonstrated a measurable long‐range coupling constant (⁴J_H2,H6) for the equatorial conformer, although ⁴J_H2,H4 and ⁴J_H4,H6 were not observed; as a consequence, it is inferred that the carbonyl group plays an important role particularly due to hyperconjugative interactions σ_C2H2→π*_C═O and σ_C6H6→π*_C═O. In the present study, NBO analysis and coupling constant calculations were performed to cyclohexanone and cyclohexanethione alpha substituted with F, Cl, and Br, aiming to evaluate the halogen effect and acceptor character of the π* orbital on the long‐range coupling pathway. The σ_C2H2→π*_C1═Y and σ_C6H6→π*_C1═Y (Y═O and S) hyperconjugative interactions for the equatorial conformer indeed contribute for the ⁴J_H2,H6 transmission mechanism_. Surprisingly, the ⁴J_H2,H6 value is higher for the carbonyl compounds, although the interactions σ_C2H2→π*_C═Y and σ_C6H6→π*_C═Y are more efficient for the thiocarbonyl compounds. Accordingly, the Fermi contact (FC) contribution for the thiocarbonyl compounds decays deeper than in ketones, thus reducing more the ⁴J_H2,H6 values. Moreover, both π_C═S→σ*_C─X and π_C═S→σ*_C─H interactions seem to be stronger in thiocarbonyl than in carbonylic compounds. The implicit solvent effect (DMSO and water) on the coupling constant values was negligible when compared with the gas phase. On the other hand, an explicit solvent effect was found and ⁴J_H2,H6 for the thiocarbonyl compounds appeared to be more sensitive than for the cyclohexanones.     

SQSQh: 1H‐detected SQ–SQ experiment for determination of signed silicon–carbon coupling constants

A new variant of SQ–SQ pulse sequence (SQSQh) for relative sign determination and detection of small silicon–carbon couplings over more than one bond is presented. In the SQSQh sequence, proton detection replaces carbon detection used in the original SQ–SQ pulse sequence (SQSQc). The theoretical gain in sensitivity was experimentally tested on two samples (trimethylsiloxyethane, 1, and 1,2,4‐tris(trimethylsiloxy)benzene, 2), the experimentally found gain provided by the SQSQh over the SQSQc method varied between 6 and 8. The method can be applied to linear spin systems, i.e. to systems where the silicon is coupled to the carbon in question and to any hydrogen not necessarily bonded to the carbon. Copyright © 2010 John Wiley & Sons, Ltd.     

Unusual open chain quinolinyl peroxol and its alcohol counterpart obtained through a modified Skraup–Doebner–Von Miller quinoline synthesis: theoretical studies and complete 1H‐ and 13C‐NMR assignments

Because of their extreme instability, it is generally difficult to synthesize and fully characterize open chain peroxides, also known as peroxols. In our attempt to investigate the mechanism of the Skraup–Doebner–Von Miller quinoline synthesis, we were able to obtain an unusual open chain peroxy‐quinoline, namely, 4‐(8‐ethoxy‐2,3‐dihydro‐1H‐cyclopenta[c]quinolin‐4‐yl)butane‐1‐peroxol (1), and its alcohol counterpart, namely 4‐(8‐ethoxy‐2,3‐dihydro‐1H‐cyclopenta[c]quinolin‐4‐yl)butan‐1‐ol (2) obtained as a side product during the same reaction. Although structurally similar, these two compounds appeared to display some very distinct physical and spectroscopic characteristics. This work reports detailed NMR studies and full ¹H and ¹³ C NMR assignments for these two compounds. These assignments are based upon the analysis of the NMR spectra of these compounds including ¹H, ¹³ C, COSY, gHSQC and gHMBC. The effect of the peroxide functional group on the chemical shift of neighboring carbons and protons was also investigated by comparing the NMR data of these two compounds. Furthermore, the effects of potential hydrogen bondings in 1, 2, and possible 1–1 dimer, 2–2 dimer and in prototypical model systems, as well as the stability of these compounds, were investigated computationally. The computed dissociation energies and NMR data support the interpretation of the experimental data. Copyright © 2012 John Wiley & Sons, Ltd.     

Efficient measurement of the sign and the magnitude of long‐range proton‐carbon coupling constants from a spin‐state‐selective HSQMBC‐COSY experiment

A spin state‐selective Heteronuclear Single‐Quantum Multiple‐Bond Connectivities (HSQMBC‐COSY) experiment is proposed to measure the sign and the magnitude of long‐range proton‐carbon coupling constants (ⁿJ(CH); n > 1) either for protonated or for non‐protonated carbons in small molecules. The simple substitution of the selective 180° ¹H pulse in the original selHSQMBC pulse scheme by a hard one allows the simultaneous evolution of both proton‐proton and proton‐carbon coupling constants during the refocusing period and enables a final COSY transfer between coupled protons. The successful implementation of the IPAP principle leads to separate mixed‐phase α/β cross‐peaks from which ⁿJ(CH) values can be easily measured by analyzing their relative frequency displacements in the detected dimension. Copyright © 2012 John Wiley & Sons, Ltd.     

Synthesis,Structure, and Characterization of 3, 4′‐Bis‐1H‐1, 2,4‐triazolium Picrate Salt: A New High‐Energy Density Material

The environmentally friendly high‐energy density salt (TRTR)(PA) (TRTR = 3, 4′‐bis‐1, 2,4‐1H‐triazole, PA = 2, 4,6‐trinitrophenol, picric acid) was synthesized and characterized. The X‐ray single crystal diffraction results illustrate that the structure of title salt belongs to the monoclinic system, space group P2₁/c. Many parallel relationships exist in the molecule, as well as a strong intramolecular π–π stacking interaction. The DSC result shows only one exothermal decomposition step at 229.1 °C. The TG‐DTG curve demonstrates a 75.9 % mass loss from 180 °C to 300 °C at a rate of 3.01 % · K^–1. Experimental data show that the combustion heat approximately equals to TNT (–15.22 MJ · kg^–1) and the enthalpy of formation is +332.2 kJ · mol^–1. Non–isothermal kinetic and thermodynamic parameters were obtained by two methods (Kissinger and Ozawa). Detonation pressure and velocity were calculated to be 23.4 GPa and 7.32 km · s^–1, respectively. Additionally, the sensitivities towards impact and friction were assessed with relevant standard methods.