Heteronuclear Multiple Quantum Correlation Research Articles

Spin-Noise-Detected Two-Dimensional Nuclear Magnetic Resonance at Triple Sensitivity.

A major breakthrough in speed and sensitivity of 2 D spin‐noise‐detected NMR is achieved owing to a new acquisition and processing scheme called “double block usage” (DBU) that utilizes each recorded noise block in two independent cross‐correlations. The mixing, evolution, and acquisition periods are repeated head‐to‐tail without any recovery delays and well‐known building blocks of multidimensional NMR (constant‐time evolution and quadrature detection in the indirect dimension as well as pulsed field gradients) provide further enhancement and artifact suppression. Modified timing of the receiver electronics eliminates spurious random excitation. We achieve a threefold sensitivity increase over the original snHMQC (spin‐noise‐detected heteronuclear multiple quantum correlation) experiment (K. Chandra et al., J. Phys. Chem. Lett. 2013, 4, 3853) and demonstrate the feasibility of spin‐noise‐detected long‐range correlation.

Heteronuclear Correlation Experiments Such as Heteronuclear Single-Quantum Correlation Spectroscopy (HSQC), Heteronuclear Multiple-Quantum Correlation Spectroscopy (HMQC) and Heteronuclear Multiple-Bond Correlation Spectroscopy (HMBC) Comparative Study On Malignant and Benign Human Endocrinology and Thyroid Cancer Cells and Tissues Under Synchrotron Radiation

Heteronuclear Correlation Experiments Such as Heteronuclear Single-Quantum Correlation Spectroscopy (HSQC), Heteronuclear Multiple-Quantum Correlation Spectroscopy (HMQC) and Heteronuclear Multiple-Bond Correlation Spectroscopy (HMBC) Comparative Study On Malignant and Benign Human Endocrinology and Thyroid Cancer Cells and Tissues Under Synchrotron Radiation

Platinum Complexes with Chelating Acyclic Aminocarbene Ligands Work as Catalysts for Hydrosilylation of Alkynes.

This work describes the preparation of a series of platinum–aminocarbene complexes [PtCl{C(N=Ca(C6R2R3R4R5CONb))=N(H)R1}(CNR1)]a–b (8–19, 65–75% isolated yield) via the reaction of cis-[PtCl2(CNR1)2] (R1 = Cy 1, t-Bu 2, Xyl 3, 2-Cl-6-MeC6H34) with 3-iminoisoindolin-1-ones HN=Ca(C6R2R3R4R5CONbH) (R2–R5 = H 5; R3 = Me, R2, R4, R5 = H 6; R3, R4 = Cl, R2, R5 = H 7). New complexes 17–19 were characterized by elemental analyses (C, H, N), ESI+-MS, Fourier transform infrared spectroscopy (FT-IR), one-dimensional (1H, 13C{1H}), and two-dimensional (1H,1H correlation spectroscopy (COSY), 1H,13C heteronuclear multiple quantum correlation (HMQC)/1H,13C heteronuclear single quantum coherence (HSQC), 1H,13C heteronuclear multiple bond correlation (HMBC)) NMR spectroscopy, and authenticity of known species 8–16 was confirmed by FT-IR and 1H and 13C{1H} NMR. Complexes 8–19 were assessed as catalysts for hydrosilylation of terminal alkynes with hydrosilanes to give vinyl silanes, and complex [PtCl{C(N=Ca(C6H3(5-Me)CONb))=N(H)(2-Cl-6-MeC6H3)}{CN(2-Cl-6-MeC6H3)}]a−b (18) showed the highest catalytic activity. The catalytic system proposed operates at 80–100 °C for 4–6 h in toluene and with catalyst loading of 0.1 mol %, enabling the reaction of a number of terminal alkynes (PhC≡CH, t-BuC≡CH, and 4-(t-Bu)C6H4C≡CH) with hydrosilanes (Et3SiH, Pr3SiH, i-Pr3SiH, and PhMe2SiH). Target vinyl silanes were prepared in 48–95% yields (as a mixture of α/β isomers) and with maximum turnover number of 8.4 × 103. Hydrosilylation of internal alkynes (PhC≡CPh, Me(CH2)2C≡C(CH2)2Me, and PhC≡CMe) with hydrosilanes (Et3SiH, PhMe2SiH) led to the corresponding trisubstituted silylated alkenes in 86–94% yields. Initial observations on the mechanism of the catalytic action of platinum–ADC catalysts 8–19 suggested a molecular catalytic cycle.

Isolation, elucidation, and molecular docking studies of active compounds from Phyllanthus niruri with angiotensin-converting enzyme inhibition

Background: Phyllanthus niruri, in Indonesia, is known as “Meniran” has a long history of use in ethnic or traditional medicine worldwide, mainly as an antihypertensive agent. Objective: The present study was designed to isolate and identify active compounds with angiotensin-converting enzyme (ACE) inhibition activity from P. niruri herb and confirm the mechanism of action, affinity, and domain specificity interactions of the isolated compounds. Materials and Methods: Some fractions of P. niruri methanolic extract were subjected to column chromatography and preparative thin-layer chromatography to get active compounds. Structural elucidation was determined via spectroscopic methods. ACE inhibition activity was measured using hippuryl-L-histidyl-L-leucine as a substrate in vitro assay. Furthermore, confirmation of the mechanism of action, affinity, and domain specificity interaction of the isolated compounds on ACE complex macromolecule (protein database id: 1O86) was performed by in silico molecular docking studies. Results: In this work, four active compounds were isolated from aerial part of P. niruri, including hypophyllantin (50% inhibition concentration [IC50] = 0.180 μg/mL), phyllantin (IC50 = 0.140 μg/mL), methyl gallate (IC50 = 0.015 μg/mL), and quercetin 3-O-β-D-glucopyranosyl-(1'''-6'')-α-rhamnoside (IC50 = 0.086 μg/mL). In silico molecular docking method emphasizes ligand-residue interactions, thereby predicting the inhibitory activity of these compounds. After docking to an ACE complex macromolecule, quercetin 3-O-β-D-glucopyranosyl-(1'''-6'')-α-rhamnoside obtained more interactions than lisinopril. Conclusion: The results were obtained from in silico and in vitro experiments and confirm the potential active compound is an ACE inhibitor and a new antihypertensive agent. Abbreviations Used: P. niruri: Phyllanthus niruri; ACE: Angiotensin-converting enzyme; HHL: Hippuryl-L-histidyl-L-leucine; HA: Hippuric acid; PDB: Protein database; IC50: 50% inhibition concentration; FH: N-hexane fraction; FE: Ethyl acetate fraction; TLC: Thin layer chromatography; UV-VIS: Ultraviolet-visible; NMR: nuclear magnetic resonance; FTIR: Fourier–Transform infrared; MS: Mass spectrometry; HMQC: Heteronuclear Multiple-Quantum Correlation; HMBC: Heteronuclear multiple bond correlation; TADOK: Tugas Akhir Mahasiswa Doktor.

SOFAST-HMQC-an efficient tool for metabolomics.

Nuclear magnetic resonance (NMR)-based metabolomics relies mostly on 1D NMR; however, the technique is limited by overlap of the signals from the metabolites. In order to circumvent this problem, 2D 1H-13C correlation spectroscopy techniques are often used. However owing to poorer natural abundance and gyromagnetic ratio of 13C, the acquisition time for 2D 1H-13C heteronuclear single quantum coherence spectroscopy (HSQC) is long. This makes it almost impossible to be used in high throughput study. We have reported the application of selective optimized flip angle short transient (SOFAST) technique coupled to heteronuclear multiple quantum correlation (HMQC) along with nonlinear sampling (NUS) in urine and serum samples. This technique takes sevenfold less experimental time than the conventional 1H-13C HSQC experiment with retention of almost all molecular information. Hence, this can be used for high throughput study. Graphical abstract SOFAST-HMQC is a two-dimensional NMR technique that significantly decreases experimental time without loss of information. This technique is applied in complex biofluid samples that are used for high throughput metabolomics studies and shows promise of better information recovery than conventional two-dimensional NMR technique in shorter time.

Synthesis, modeling and biological evaluation of hybrids from pyrazolo[1,5c]pyrimidine as antileishmanial agents.

A new series of pyrazolo[1,5-c]pyrimidines were synthesized by different hybridization strategies. All structures were confirmed by IR, 1H, 13C, 1H-13C heteronuclear multiple-quantum correlation (HMQC) spectra and microanalysis. They were evaluated for their in vitro antileishmanial activity against miltefosine and amphotericin B deoxycholate as reference drugs. The most active compounds 2a and 9a demonstrated superior potencies to miltefosine by ten- and six-fold, respectively, for the promastigote form, and by 5.5-fold for the amastigote form. Their binding scenario to Leishmania major pteridine reductase was rationalized by docking experiments. In addition, all compounds were safe for the experimental animals orally up to 150mg/kg and parenterally up to 75mg/kg. This study provides novel chemotype class for antileishmanial activity. [Formula: see text].

71Ga-77Se connectivities and proximities in gallium selenide crystal and glass probed by solid-state NMR

We introduce two-dimensional (2D) 71Ga-77Se through-bond and through-space correlation experiments. Such correlations are achieved using (i) the J-mediated Refocused Insensitive Nuclei Enhanced by Polarization Transfer (J-RINEPT) method with 71Ga excitation and 77Se Carr-Purcell-Meiboon-Gill (CPMG) detection, as well as (ii) the J- or dipolar-mediated Hetero-nuclear Multiple-Quantum Correlation (J- or D-HMQC) schemes with 71Ga excitation and quadrupolar CPMG (QCPMG) detection. These methods are applied to the crystalline β-Ga2Se3 and the 0.2Ga2Se3-0.8GeSe2 glass. Such glass leads to a homogeneous and reproducible glass–ceramic, which is a good alternative to single-crystalline Ge and polycrystalline ZnSe materials for making lenses transparent in the IR range for thermal imaging applications. We show that 2D 71Ga-77Se correlation experiments allow resolving the 77Se signals of molecular units, which are not resolved in the 1D 77Se CPMG spectrum. Additionally, the build-up curves of the J-RINEPT and the J-HMQC experiments allow the estimate of the 71Ga-77Se J-couplings via one and three-bonds in the three-dimensional network of β-Ga2Se3. Furthermore, these build-up curves show that the one-bond 1J71Ga-77Se couplings in the 0.2Ga2Se3-0.8GeSe2 glass are similar to those measured for β-Ga2Se3. We also report 2D 71Ga Satellite Transition Magic-Angle Spinning (STMAS) spectrum of β-Ga2Se3 using QCPMG detection at high magnetic field and high Magic-Angle Spinning frequency using large radio frequency field. Such spectrum allows separating the signal of β-Ga2Se3 and that of an impurity.

γ-Independent through-space hetero-nuclear correlation between spin-1/2 and quadrupolar nuclei in solids

We introduce novel sequences using indirect detection to correlate quadrupolar nuclei and spin-1/2 isotopes, other than 1H and 19F. These sequences use γ-encoded symmetry-based RNnν schemes that reintroduce the space component |m| = 1 of the heteronuclear dipolar coupling. These schemes can be applied to the indirectly detected spin in Dipolar-mediated Heteronuclear Multiple-Quantum Correlation (D-HMQC) sequence or to the detected isotope in a novel sequence, named Dipolar-mediated Heteronuclear Universal-Quantum Correlation (D-HUQC). We show that the signal of these sequences using γ-encoded recoupling does not depend on the γ Euler angle relating the inter-nuclear vector between the coupled spins to the MAS rotor-fixed frame. Therefore, the transfer efficiency of these sequences is in principle higher than that of D-HMQC methods using non-γ-encoded recoupling. Furthermore, numerical simulations show that the heteronuclear correlation experiments employing γ-encoded recoupling are more robust to Chemical Shift Anisotropy (CSA) of the irradiated spin and MAS frequency fluctuations. These results are confirmed by 13C-{15N} heteronuclear correlation on glycine and 31P-27Al ones on VPI-5 and Na7(AlP2O7)4PO4. These experiments indicate that R1635 recoupling produces the highest signal-to-noise ratio in heteronuclear correlation 2D experiments when the detected spin-1/2 nuclei are subject to large CSA.

Efficacy of extracts and iridoid glucosides from Pentas lanceolata on humoral and cell-mediated immune response of viral vaccine

The 80% aqueous methanol extract of Pentas lanceolata (Rubiaceae) was partitioned with n-hexane, ether, ethyl acetate extract, and n-butanol extract. The immunomodulatory role of the five extracts on humoral and cell-mediated immune response of viral vaccine in specific pathogen-free chicken vaccinated against Newcastle disease virus was carried out. The active fractions, n-butanol, was fractioned by silica-column chromatography and active sub-fraction were separated using reverse phase-high performance liquid chromatography. Two new iridoids, namely, 13R-methoxy-epi-gaertneroside 2 and 13S-methoxy-epi-gaertneroside 3, and three known, 13R-epi-gaertneroside 1, a mixture of E-uenfoside 4 and Z-uenfoside 5, were isolated from the active sub-fractions. Their chemical structures were achieved by the extensive 1D and 2D nuclear magnetic resonance (1H and 13C, correlation spectroscopy, heteronuclear multiple quantum correlation, and heteronuclear multiple bond correlation), IR as well as HREIMS spectral data. Stimulation of both seroresponses was observed, especially those of ethyl acetate extract, n-butanol extract, and compound 1. Remarkable effective increase of the antibody titers; lymphocyte and macrophage cells in blood were recorded. The study suggested that the possible role was played by P. lanceolata aerial parts n-butanol, ethyl acetate, and three iridoids 1, 4, and 5 in immunity (humoral and cellular) against Newcastle disease which is severely endangering out the poultry industry by causing economic losses.

Low-power broadband solid-state MAS NMR of 14N.

We propose two broadband pulse schemes for 14N solid-state magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) that achieves (i) complete population inversion and (ii) efficient excitation of the double-quantum spectrum using low-power single-sideband-selective pulses. We give a comprehensive theoretical description of both schemes using a common framework that is based on the jolting-frame formalism of Caravatti et al. [J. Magn. Reson. 55, 88 (1983)]. This formalism is used to determine for the first time that we can obtain complete population inversion of 14N under low-power conditions, which we do here using single-sideband-selective adiabatic pulses. It is then used to predict that double-quantum coherences can be excited using low-power single-sideband-selective pulses. We then proceed to design a new experimental scheme for double-quantum excitation. The final double-quantum excitation pulse scheme is easily incorporated into other NMR experiments, as demonstrated here for double quantum-single quantum 14N correlation spectroscopy, and 1H-14N dipolar heteronuclear multiple-quantum correlation experiments. These pulses and irradiation schemes are evaluated numerically using simulations on single crystals and full powders, as well as experimentally on ammonium oxalate ((NH4)2C2O4) at moderate MAS and glycine at ultra-fast MAS. The performance of these new NMR methods is found to be very high, with population inversion efficiencies of 100% and double-quantum excitation efficiencies of 30%-50%, which are hitherto unprecedented for the low radiofrequency field amplitudes, up to the spinning frequency, that are used here.

Proton detection of MAS solid-state NMR spectra of half-integer quadrupolar nuclei

Fast magic angle spinning (MAS) and proton detection has found widespread application to enhance the sensitivity of solid-state NMR experiments with spin-1/2 nuclei such as 13C, 15N and 29Si, however, this approach is not yet routinely applied to half-integer quadrupolar nuclei. Here we have investigated the feasibility of using fast MAS and proton detection to enhance the sensitivity of solid-state NMR experiments with half-integer quadrupolar nuclei. The previously described dipolar hetero-nuclear multiple quantum correlation (D-HMQC) and dipolar refocused insensitive nuclei enhanced by polarization transfer (D-RINEPT) pulse sequences were used for proton detection of half-integer quadrupolar nuclei. Quantitative comparisons of signal-to-noise ratios and the sensitivity of proton detected D-HMQC and D-RINEPT and direct detection spin echo and quadrupolar Carr-Purcell Meiboom-Gill (QCPMG) solid-state NMR spectra, demonstrate that one dimensional proton detected experiments can provide sensitivity similar to or exceeding that obtainable with direct detection QCPMG experiments. 2D D-HMQC and D-RINEPT experiments provide less sensitivity than QCPMG experiments but proton detected 2D hetero-nuclear correlation solid-state NMR spectra of half-integer nuclei can still be acquired in about the same time as a 1D spin echo spectrum. Notably, the rarely used D-RINEPT pulse sequence is found to provide similar, or better sensitivity than D-HMQC in some cases. Proton detected D-RINEPT benefits from the short longitudinal relaxation times (T1) normally associated with half-integer quadrupolar nuclei, it can be combined with existing signal enhancement methods for quadrupolar nuclei, and t1-noise in the indirect dimension can easily be removed by pre-saturation of the 1H nuclei. The rapid acquisition of proton detected 2D HETCOR solid-state NMR spectra of a range of half-integer quadrupolar nuclei such as 17O, 27Al, 35Cl and 71Ga is demonstrated.

Synthesis and use of dioxime ligands for treatment of leukemia and colon cancer cells

Two new vicinal dioxime ligands containing thiosemicarbazone units (L1H2 and L2H2) were synthesized and characterized using 1H NMR, 13C NMR, heteronuclear multiple quantum correlation, mass, infrared and UV–visible spectroscopies, elemental analysis and magnetic susceptibility measurements. In addition, homotrinuclear nickel(II), copper(II) and cobalt(II) complexes with a metal‐to‐ligand ratio of 3:2 for L1H2 and L2H2 were prepared. Synthesis of nickel(II) complex containing a BF2+ bridge was carried out using a precursor hydrogen‐bridged nickel(II) complex via the template effect. All metal–ligand complexes were tested against two human cancer cell lines (HL‐60 and HT‐29) for their antiproliferative and apoptotic activities. The results showed that [Co(L2H)2(H2O)2] and [Ni(L2H)2] exhibited the strongest antiproliferative activity with IpC50 values ranging between 5 and 10 μM, while [Co(L2H)2(H2O)2] and [Ni(L2H)2] both induced necrosis of HT‐29 cells and 60 and 65% apoptosis in HL‐60 cells, respectively.

Isolation and identification of compounds from Phaleria macrocarpa (Scheff.) Boerl fruit extract

ObjectiveTo identify and isolate the chemical compounds of Phaleria macrocarpa (P. macrocarpa) fruit ethanolic extract. MethodsDried fruit of P. macrocarpa was extracted with 90% ethanol and partitioned between n-hexane/H2O and ethyl acetate/H2O. The organic layer was fractionated by various stationary phase and identified by using combined data of 1D [(proton nuclear magnetic resonance (NMR), carbon-13 NMR)], 2D-NMR (heteronuclear multiple-quantum correlation and heteronuclear multiple-bond correlation), and mass spectrum. ResultsPurification of n-hexane and ethyl acetate fractions from ethanolic extract of P. macrocarpa fruit resulted in isolation of nine compounds. ConclusionsA new compound was isolated and identified as glyceryl pentacosanoate. Also, two xanthones, which are 1,7-dihydroxy-3,6-dimethoxyxanthone and 1,6,7-trihydroxy-3-methoxyxanthone, are firstly reported to be isolated from P. macrocarpa.

Chemical Components from Aloe and their Inhibition of Indoleamine 2, 3-dioxygenase.

Background:In Korea, Aloe is routinely ingested as a traditional medicine or as a component of health beverages.Objective:To research the inhibition of indoleamine 2, 3-dioxygenase (IDO) activities of components from Aloe.Materials and Methods:the compounds were isolated by a combination of silica gel and YMC Rp-18 column chromatography, and their structures were identified by analysis of spectroscopic data (1D, 2D-NMR, and MS). All of the isolated compounds were examined for their ability to inhibit IDO, which actively suppresses immune functions by catalyzing the rate limiting reaction in the conversion of tryptophan to kynurenine.Results:In this phytochemical study, 18 known compounds were isolated from aqueous dissolved Aloe exudates. All of the isolated compounds were examined for their ability to inhibit IDO activities for a series of anthraquinone derivatives (1-7) isolated from the Aloe extract; the IC50 values of these compounds ranged from 39.41 to 53.93 µM. Enzyme kinetic studies of their modes of inhibition indicated that all of the compounds were uncompetitive inhibitors.Conclusion:The aqueous dissolved Aloe exudate can be used as a source of novel natural IDO inhibitors and merit testing as therapeutic agents in the treatments of cancer and immunopathologic diseases, such as autoimmune, inflammatory, and allergic disorders.SUMMARY In this study, 18 known compounds were isolated from aqueous dissolved Aloe exudates. All of the isolated compounds were examined for their ability to inhibit indoleamine 2, 3-dioxygenase (IDO) activities for a series of anthraquinone derivatives (1−7) isolated from the Aloe extract. Abbreviation used: IDO: inhibit indoleamine 2, 3-dioxygenase, TMS: tetramethylsilane, HMQC: heteronuclear multiple quantum correlation, HMBC: heteronuclear multiple bond correlation, COSY: 1H-1H correlation spectroscopy, ESI-MS: Electrospray ionization mass spectrometry, DMSO: dimethyl sulfoxide

Quassinoids from the Root of Eurycoma longifolia and Their Antiproliferative Activity on Human Cancer Cell Lines.

Background:The roots of Eurycoma longifolia Jack have traditionally been used as an aphrodisiac tonic besides the other remedies for boils, fever, bleeding gums, and wound ulcer. Recently, the antiproliferative activity of E. longifolia has been reported and remained attractive to natural chemists.Objective:The objective of this study was to study on antiproliferative compounds from the root of E. longifolia.Materials and Methods:Column chromatography was used to separate individual compounds, spectroscopic data including nuclear magnetic resonances and mass spectrometry were analyzed to determine the chemical structure of the isolates and for biological testing, antiproliferative activity of compounds was tested on seven human cancer cell lines (KATO III, HCT-15, Colo205, HepG2, PC-3, Jurkat, HL-60) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.Results:Nine quassinoids including a new C19 longilactone-type quassinoid glycoside were characterized from the roots of the title plant. Among them, the major quassinoid eurycomanone exhibited selectively potential antiproliferative activities on the leukemia cell lines (HL-60 and Jurkat) and had very low toxic effects on normal skin fibroblast cell line (NB1RGB).Conclusion:The current study reveals one new quassinoid glycoside and the potential active component (eurycomanone) from E. longifolia for the leukemia treatment.SUMMARY Nine quassinoids (1-9) including one new quassinoid glycoside (9) and eight known ones were isolated from the roots of Eurycoma longifoliaThe structure of the new quassinoid 9 was determined by extensive chemical and spectroscopic analysesThe major quassinoid, eurycomanone (3), exhibited selectively potential antiproliferative activities on both Jurkat and HL-60 leukemia cells and had very low toxic effects on normal skin fibroblast cell line (NB1RGB). Abbreviations used: COSY: Correlation spectroscopy; HMBC: Heteronuclear multiple-bond correlation; HMQC: Heteronuclear multiple quantum correlation; NMR: Nuclear magnetic resonance; NOESY: Nuclear Overhauser enhancement spectroscopy; TLC: Thin layer chromatography.

Advanced NMR Methods and DFT Calculations on the Regioselective Deprotonation and Functionalization of 1,1′‐Methylenebis(3‐methylimidazole‐2‐thione)

Depending on the temperature, the twofold deprotonation of 1,1′‐methylenebis(3‐methylimidazole‐2‐thione) (1) and the subsequent reaction with 2 equiv. of trimethylsilyl chloride (TMSCl) gives two different bis‐TMS‐functionalized isomers, namely, 1,1′‐methylenebis(3‐methyl‐4‐trimethylsilylimidazole‐2‐thione) (2) and 1,1′‐methylenebis(3‐methyl‐5‐trimethylsilylimidazole‐2‐thione) (3). The cyclic dimethylsilyl‐bridged derivative 1,1′‐methylene‐5,5′‐dimethylsilylenebis(3‐methylimidazole‐2‐thione) (4) can also be obtained, corroborating the 5/5′ addition under certain conditions. All compounds have been examined by multinuclear 1D and 2D NMR experiments (1–4) together with single‐crystal X‐ray diffraction (3 and 4). Additionally, the dilithiated species 5 was synthesized by reacting 1 with 2 equiv. of nBuLi at ambient temperature in solution (THF). 1H and 7Li pulsed field‐gradient spin‐echo (PGSE) NMR, 7Li–1H heteronuclear Overhauser spectroscopy (HOESY), gradient heteronuclear multiple quantum correlation (gHMQC) and gradient heteronuclear multiple bond correlation (gHMBC) experiments showed that 5 exists as a monomeric contact ion pair (CIP) in THF solution. On the contrary, the X‐ray diffraction analysis of 5 revealed a polymeric chain, which can be described as [{5(thf)2}2]∞. Quantum chemical DFT and MP2 calculations were also conducted to determine the energies required for the deprotonation of 1. These results explain the regioselective deprotonation of 1 by CIP formation depending on the temperature and fully support the results of the synthetic and spectroscopic experiments.

Logic Structure Determination (LSD) as a Computer Assisted Structure Elucidation (Case) for Molecular Structure Determination of Cytotoxic Cembranoids from Soft Coral

The tropical Indonesian soft corals are a valuable resources that produce pharmacological cytotoxic cembranoids. However, manual structure determination into these compounds requires adequate knowledge of organic chemistry. This study presents the application of Logic Structure Determination (LSD), as a freeware Computer Assisted Structure Elucidation (CASE) for automatic molecular structure determination of cembranoid compounds from soft corals species. 12 Nuclear Magnetic Resonance (NMR) dataset of cytotoxic cembranoids were used to evaluate the accuracy of LSD in generating the possible structures. Results of this study shows LSD generated numerous possible molecular structures, as the data input file derived only from 2D-NMR HMQC (Heteronuclear Multiple-Quantum Correlation), COSY (Homonuclear Correlation Spectroscopy), and HMBC (Heteronuclear Multiple Bond Correlation). The accuracy significantly enhanced (only 2-4 possible cembranoid structures from each NMR dataset) with addition of H2BC (Heteronuclear 2 Bond Correlation) experimental data. This may indicates that VLRC (Very Long-Range Correlations) affects significantly to LSD capability. Furthermore, LSD with direct 2 bond NMR experimental data is a reliable CASE technique for identification of cembranoid compounds. In general, this freeware-CASE is potential to be applied to other type of small molecule compounds and may serves as a potential solution for elucidation bottleneck step in Indonesian natural products studies.

Multifunctional quinoline-triazole derivatives as potential modulators of amyloid-β peptide aggregation

Metal ion dyshomeostasis is hypothesized to play a role in the toxicity and aggregation of the amyloid beta (Aβ) peptide, contributing to Alzheimer's disease (AD) pathology. We report on the synthesis and metal complexation ability of three bidentate quinoline-triazole derivatives 3-(4-(quinolin-2-yl)-1H-1,2,3-triazol-1-yl)propan-1-ol (QOH), 4-(2-(4-(quinolin-2-yl)-1H-1,2,3-triazol-1-yl)ethyl)morpholine (QMorph), and 4-(2-(4-(quinolin-2-yl)-1H-1,2,3-triazol-1-yl)ethyl)thiomorpholine (QTMorph). We further study the utility of these ligands to modulate Aβ peptide aggregation processes in the presence and absence of Cu2+ ions. Ligand-peptide interactions were first investigated using both 2-D 1H–15N band-selective optimized flip angle short transient heteronuclear multiple quantum correlation (SOFAST-HMQC) NMR spectroscopy and molecular modeling techniques, indicating interactions with glutamic acid (E3) and several residues in the hydrophobic region of Aβ. Native gel electrophoresis with western blotting along with transmission electron microscopy provided information on the ability of each ligand to modulate Aβ aggregation. While the ligands alone did not modify Aβ peptide aggregation at the 24h timepoint, signifying relatively weak ligand-peptide interactions, the ligands did modify the aggregation profile of the peptide in the presence of stoichiometric and suprastoichiometric Cu. Interestingly, the thioether derivative QTMorph exhibited the most pronounced effect on peptide aggregation in the presence of Cu. Overall, the quinoline-triazole ligand series were shown to interact with the hydrophobic region of the Aβ peptide, and modulate the Cu-Aβ aggregation process.

Site-resolved multiple-quantum filtered correlations and distance measurements by magic-angle spinning NMR: Theory and applications to spins with weak to vanishing quadrupolar couplings

We discuss and analyze four magic-angle spinning solid-state NMR methods that can be used to measure internuclear distances and to obtain correlation spectra between a spin I = 1/2 and a half-integer spin S > 1/2 having a small quadrupolar coupling constant. Three of the methods are based on the heteronuclear multiple-quantum and single-quantum correlation experiments, that is, high rank tensors that involve the half spin and the quadrupolar spin are generated. Here, both zero and single-quantum coherence of the half spins are allowed and various coherence orders of the quadrupolar spin are generated, and filtered, via active recoupling of the dipolar interaction. As a result of generating coherence orders larger than one, the spectral resolution for the quadrupolar nucleus increases linearly with the coherence order. Since the formation of high rank tensors is independent of the existence of a finite quadrupolar interaction, these experiments are also suitable to materials in which there is high symmetry around the quadrupolar spin. A fourth experiment is based on the initial quadrupolar-driven excitation of symmetric high order coherences (up to p = 2S, where S is the spin number) and subsequently generating by the heteronuclear dipolar interaction higher rank (l + 1 or higher) tensors that involve also the half spins. Due to the nature of this technique, it also provides information on the relative orientations of the quadrupolar and dipolar interaction tensors. For the ideal case in which the pulses are sufficiently strong with respect to other interactions, we derive analytical expressions for all experiments as well as for the transferred echo double resonance experiment involving a quadrupolar spin. We show by comparison of the fitting of simulations and the analytical expressions to experimental data that the analytical expressions are sufficiently accurate to provide experimental (7)Li-(13)C distances in a complex of lithium, glycine, and water. Discussion of the regime for which such an approach is valid is given.

The Heteronuclear Multiple-Quantum Correlation Experiment: Perspective from Classical Vectors, Nonclassical Vectors, and Product Operators

It is usually accepted that most 2D-NMR experiments cannot be approached using classical models. Instructors argue that Product Operators (PO) or density matrix formalisms are the only alternative to get insights into complex spin evolution for experiments involving Multiple-Quantum Coherence, such as the Heteronuclear Multiple-Quantum Correlation (HMQC) technique. Nevertheless, in recent years, several contributions have been published to provide vectorial descriptions for the HMQC taking PO formalism as the starting point. In this work we provide a graphical representation of the HMQC experiment, taking the basic elements of Bloch’s vector model as building blocks. This description bears an intuitive and comfortable understanding of spin evolution during the pulse sequence, for those who are novice in 2D-NMR. Finally, this classical vectorial depiction is tested against the PO formalism and nonclassical vectors, conveying the didactic advantage of shedding light on a single phenomenon from different perspectives. This comparative approach could be useful to introduce PO and nonclassical vectors for advanced upper-division undergraduate and graduate education.