xianqi kong - Academia.edu (original) (raw)
Papers by xianqi kong
Journal of Physical Chemistry A, Jan 17, 2012
A variety of experimental solid-state nuclear magnetic resonance (NMR) techniques has been used t... more A variety of experimental solid-state nuclear magnetic resonance (NMR) techniques has been used to characterize each of the elements in 2-aminoethane sulfonic acid (taurine). A combination of 15 N cross-polarization magic angle spinning (CPMAS), 14 N ultrawideline, and 14 N overtone experiments enabled a determination of the relative orientation of the nitrogen electric field gradient and chemical shift tensors. 17 O spectra recorded from an isotopically enriched taurine sample at multiple magnetic fields allowed the three nonequivalent oxygen sites to be distinguished, and NMR parameters calculated from a neutron diffraction structure using density functional theory allowed the assignment of the 17 O parameters to the correct crystallographic sites. This is the first time that a complete set of 17 O NMR tensors are reported for a sulfonate group. In combination with 1 H and 13 C MAS spectra, as well as a previously reported 33 S NMR study, this provides a very broad set of NMR data for this relatively simple organic molecule, making it a potentially useful structure on which to test DFT calculation methods (particularly for the quadrupolar nuclei 14 N, 17 O, and 33 S) or NMR crystallography approaches.
Tetrahedron Letters, Dec 1, 2007
A practical synthetic route to various 2-alkylpropane-1,3-sultones, the key intermediates for the... more A practical synthetic route to various 2-alkylpropane-1,3-sultones, the key intermediates for the preparation of 2-substituted homotaurines as analogs of tramiprosate, was developed.
ChemInform, Aug 19, 2010
An Improved Method for the Regioselective Synthesis of Highly Substituted Quinolines from Morita-... more An Improved Method for the Regioselective Synthesis of Highly Substituted Quinolines from Morita-Baylis-Hillman Adducts.-The Pd-catalyzed Heck reaction of indoanilines with Morita-Baylis-Hillman adducts leads to the regioselective formation of quinoline derivatives.
The dibutylstannylene acetals of carbohydrate-derived primary-secondary 1,2-diols 4, 104, 105 and... more The dibutylstannylene acetals of carbohydrate-derived primary-secondary 1,2-diols 4, 104, 105 and 06 were found to be oxidized regiospecifically to corresponding alpha\alphaalpha-hydroxyketone derivatives in much better yields (81% to 95%) by N-bromosuccinimide in chloroform solution at room temperature than had previously been done with bromine. One of the products, 3-deoxy-1,2-O-isopropylidene-$\alpha$- scD-erythro-hexofuranos-5-ulose (10), exists to about 20% in solution as a mixture of dimers. One of the dimers can be obtained as a solid and its structure was determined tentatively by a combination of NMR experiments and MM3 molecular mechanics calculations.
Angewandte Chemie, Feb 18, 2015
We demonstrate that high-quality solid-state 17 O (I = 5/2) NMR spectra can be successfully obtai... more We demonstrate that high-quality solid-state 17 O (I = 5/2) NMR spectra can be successfully obtained for paramagnetic coordination compounds in which oxygen atoms are directly bonded to the paramagnetic metal centers. For complexes containing V(III) (S = 1), Cu(II) (S = 1/2), and Mn(III) (S = 2) metal centers, the 17 O isotropic paramagnetic shifts were found to span a range of ** This work was supported by NSERC of Canada. Y. Z. acknowledges the support from the National Institutes of Health (NIH) (GM085774). Access to the 900 MHz NMR spectrometer was provided by the National Ultrahigh Field NMR Facility for Solids (Ottawa, Canada), a national research facility funded by a consortium of Canadian universities, the Canada Foundation for Innovation, the Ontario Innovation Trust, Recherche Québec, and Bruker BioSpin and managed by the University of Ottawa (http://nmr900.ca).
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
La presente invention porte sur des sels nutritifs organiques constitues d'acide 3-amino-1-pr... more La presente invention porte sur des sels nutritifs organiques constitues d'acide 3-amino-1-propanesulfonique (homotaurine) et d'un composant cationique organique qui contribue a la valeur therapeutique et/ou nutritionnelle des sels. L'invention porte egalement sur le procede de preparation des sels nutritifs organiques et sur l'utilisation de ceux-ci comme produits nutraceutiques pour la neuroprotection et pour l'amelioration ou la protection de fonctions cognitives et de la memoire.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Bioorganic & Medicinal Chemistry
The Journal of Physical Chemistry A
Canadian journal of physiology and pharmacology, Jan 9, 2017
Metalloporphyrin, heme oxygenase (HO) inhibitors have made an important contribution to elucidati... more Metalloporphyrin, heme oxygenase (HO) inhibitors have made an important contribution to elucidating the role of HO in physiological processes. Nevertheless, their off-target effects have drawn substantial criticism, which prompted us to develop non-porphyrin, azole-based inhibitors of HO. These second-generation HO inhibitors were evaluated using spleen and brain microsomes from rats as native sources of HO-1 and HO-2, respectively. Recently, the use of azole-based inhibitors of HO has been extended to other mammalian species and, as a consequence, it will be important to characterize the inhibitors in these species. The goal of this study was to compare the inhibitory profile of imidazole- and benzimidazole-based inhibitors of HO in a breast cancer-implanted mouse to that of an untreated rat. For spleen and brain microsomes from both species, HO protein expression was determined by western blotting and concentration-response curves for imidazole- and benzimidazole-derivative inhibi...
The journal of physical chemistry. B, Nov 3, 2016
We report preparation, trapping, and solid-state (17)O NMR characterization of three unstable acy... more We report preparation, trapping, and solid-state (17)O NMR characterization of three unstable acyl-enzyme intermediates (≈ 26 kDa): p-N,N-dimethylamino-[(17)O]benzoyl-chymotrypsin, trans-o-methoxy-[(17)O]cinnamoyl-chymotrypsin, and trans-p-methoxy-[(17)O]cinnamoyl-chymotrypsin. We show that both the (17)O chemical shifts and nuclear quadrupolar parameters obtained for these acyl-enzyme intermediates in the solid state are correlated with their deacylation rate constants measured in aqueous solution. With the aid of quantum mechanical calculations, the experimental (17)O NMR parameters were interpreted as to reflect the hydrogen bonding interactions between the carbonyl (C═(17)O) functional group of the acyl moiety and the two NH groups from the protein backbone (Ser195 and Gly193) in the oxyanion hole, a general feature of all serine proteases. Our results further suggest that the (17)O chemical shift and quadrupole coupling constant display distinctly different sensitivities toward...
Solid state nuclear magnetic resonance, Jan 27, 2016
We report synthesis and solid-state (17)O NMR characterization of four site-specifically (17)O-la... more We report synthesis and solid-state (17)O NMR characterization of four site-specifically (17)O-labeled 2-acylbenzoic acids (2-RC(O)C6H4COOH) where R=H and CH3): 2-[3-(17)O]formylbenzoic acid, 2-[1,2-(17)O2]formylbenzoic acid, 2-[3-(17)O]acetylbenzoic acid, and 2-[1,2,3-(17)O3]acetylbenzoic acid. In the solid state, both 2-formyl- and 2-acetyl-benzoic acids exist as the cyclic phthalide form each containing a five-membered lactone ring and a cyclic hemiacetal/hemiketal group. Static and magic-angle-spinning (17)O NMR spectra were recorded at 14.1 and 21.1T for these compounds, from which the (17)O chemical shift and nuclear quadrupolar coupling tensors were determined for each oxygen site. These results represent the first time that (17)O NMR tensors are fully characterized for lactone, cyclic hemiacetal, and cyclic hemiketal functional groups. We also report solid-state (17)O NMR data for the cyclic hemiketal group an anticoagulant drug, warfarin. Experimental (17)O NMR tensors in t...
Angewandte Chemie (International ed. in English), Jan 22, 2017
While NMR and IR spectroscopic signatures and structural characteristics of low-barrier hydrogen ... more While NMR and IR spectroscopic signatures and structural characteristics of low-barrier hydrogen bond (LBHB) formation are well documented in the literature, direct measurement of the LBHB energy is difficult. Here, we show that solid-state (17) O NMR spectroscopy can provide unique information about the energy required to break a LBHB. Our solid-state (17) O NMR data show that the HB enthalpy of the O⋅⋅⋅H⋅⋅⋅N LBHB formed in crystalline nicotinic acid is only 7.7±0.5 kcal mol(-1) , suggesting that not all LBHBs are particularly strong.
The journal of physical chemistry. B, Nov 17, 2016
We report a combined solid-state ((1)H, (2)H, (13)C, (17)O) NMR and plane-wave density functional... more We report a combined solid-state ((1)H, (2)H, (13)C, (17)O) NMR and plane-wave density functional theory (DFT) computational study of the O···H···O low-barrier hydrogen bonds (LBHBs) in two 1,3-diketone compounds: dibenzoylmethane (1) and curcumin (2). In the solid state, both 1 and 2 exist in the cis-keto-enol tautomeric form, each exhibiting an intramolecular LBHB with a short O···O distance (2.435 Å in 1 and 2.455 Å in 2). Whereas numerous experimental (structural and spectroscopic) and computational studies have been reported for the enol isomers of 1,3-diketones, a unified picture about the proton location within an LBHB is still lacking. This work reports for the first time the solid-state (17)O NMR data for the O···H···O LBHBs in 1,3-diketones. The central conclusion of this work is that detailed information about the probability density distribution of the proton (nuclear zero-point motion) across an LBHB can be obtained from a combination of solid-state NMR and plane-wave D...
Journal of Physical Chemistry A, Jan 17, 2012
A variety of experimental solid-state nuclear magnetic resonance (NMR) techniques has been used t... more A variety of experimental solid-state nuclear magnetic resonance (NMR) techniques has been used to characterize each of the elements in 2-aminoethane sulfonic acid (taurine). A combination of 15 N cross-polarization magic angle spinning (CPMAS), 14 N ultrawideline, and 14 N overtone experiments enabled a determination of the relative orientation of the nitrogen electric field gradient and chemical shift tensors. 17 O spectra recorded from an isotopically enriched taurine sample at multiple magnetic fields allowed the three nonequivalent oxygen sites to be distinguished, and NMR parameters calculated from a neutron diffraction structure using density functional theory allowed the assignment of the 17 O parameters to the correct crystallographic sites. This is the first time that a complete set of 17 O NMR tensors are reported for a sulfonate group. In combination with 1 H and 13 C MAS spectra, as well as a previously reported 33 S NMR study, this provides a very broad set of NMR data for this relatively simple organic molecule, making it a potentially useful structure on which to test DFT calculation methods (particularly for the quadrupolar nuclei 14 N, 17 O, and 33 S) or NMR crystallography approaches.
Tetrahedron Letters, Dec 1, 2007
A practical synthetic route to various 2-alkylpropane-1,3-sultones, the key intermediates for the... more A practical synthetic route to various 2-alkylpropane-1,3-sultones, the key intermediates for the preparation of 2-substituted homotaurines as analogs of tramiprosate, was developed.
ChemInform, Aug 19, 2010
An Improved Method for the Regioselective Synthesis of Highly Substituted Quinolines from Morita-... more An Improved Method for the Regioselective Synthesis of Highly Substituted Quinolines from Morita-Baylis-Hillman Adducts.-The Pd-catalyzed Heck reaction of indoanilines with Morita-Baylis-Hillman adducts leads to the regioselective formation of quinoline derivatives.
The dibutylstannylene acetals of carbohydrate-derived primary-secondary 1,2-diols 4, 104, 105 and... more The dibutylstannylene acetals of carbohydrate-derived primary-secondary 1,2-diols 4, 104, 105 and 06 were found to be oxidized regiospecifically to corresponding alpha\alphaalpha-hydroxyketone derivatives in much better yields (81% to 95%) by N-bromosuccinimide in chloroform solution at room temperature than had previously been done with bromine. One of the products, 3-deoxy-1,2-O-isopropylidene-$\alpha$- scD-erythro-hexofuranos-5-ulose (10), exists to about 20% in solution as a mixture of dimers. One of the dimers can be obtained as a solid and its structure was determined tentatively by a combination of NMR experiments and MM3 molecular mechanics calculations.
Angewandte Chemie, Feb 18, 2015
We demonstrate that high-quality solid-state 17 O (I = 5/2) NMR spectra can be successfully obtai... more We demonstrate that high-quality solid-state 17 O (I = 5/2) NMR spectra can be successfully obtained for paramagnetic coordination compounds in which oxygen atoms are directly bonded to the paramagnetic metal centers. For complexes containing V(III) (S = 1), Cu(II) (S = 1/2), and Mn(III) (S = 2) metal centers, the 17 O isotropic paramagnetic shifts were found to span a range of ** This work was supported by NSERC of Canada. Y. Z. acknowledges the support from the National Institutes of Health (NIH) (GM085774). Access to the 900 MHz NMR spectrometer was provided by the National Ultrahigh Field NMR Facility for Solids (Ottawa, Canada), a national research facility funded by a consortium of Canadian universities, the Canada Foundation for Innovation, the Ontario Innovation Trust, Recherche Québec, and Bruker BioSpin and managed by the University of Ottawa (http://nmr900.ca).
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
La presente invention porte sur des sels nutritifs organiques constitues d'acide 3-amino-1-pr... more La presente invention porte sur des sels nutritifs organiques constitues d'acide 3-amino-1-propanesulfonique (homotaurine) et d'un composant cationique organique qui contribue a la valeur therapeutique et/ou nutritionnelle des sels. L'invention porte egalement sur le procede de preparation des sels nutritifs organiques et sur l'utilisation de ceux-ci comme produits nutraceutiques pour la neuroprotection et pour l'amelioration ou la protection de fonctions cognitives et de la memoire.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Bioorganic & Medicinal Chemistry
The Journal of Physical Chemistry A
Canadian journal of physiology and pharmacology, Jan 9, 2017
Metalloporphyrin, heme oxygenase (HO) inhibitors have made an important contribution to elucidati... more Metalloporphyrin, heme oxygenase (HO) inhibitors have made an important contribution to elucidating the role of HO in physiological processes. Nevertheless, their off-target effects have drawn substantial criticism, which prompted us to develop non-porphyrin, azole-based inhibitors of HO. These second-generation HO inhibitors were evaluated using spleen and brain microsomes from rats as native sources of HO-1 and HO-2, respectively. Recently, the use of azole-based inhibitors of HO has been extended to other mammalian species and, as a consequence, it will be important to characterize the inhibitors in these species. The goal of this study was to compare the inhibitory profile of imidazole- and benzimidazole-based inhibitors of HO in a breast cancer-implanted mouse to that of an untreated rat. For spleen and brain microsomes from both species, HO protein expression was determined by western blotting and concentration-response curves for imidazole- and benzimidazole-derivative inhibi...
The journal of physical chemistry. B, Nov 3, 2016
We report preparation, trapping, and solid-state (17)O NMR characterization of three unstable acy... more We report preparation, trapping, and solid-state (17)O NMR characterization of three unstable acyl-enzyme intermediates (≈ 26 kDa): p-N,N-dimethylamino-[(17)O]benzoyl-chymotrypsin, trans-o-methoxy-[(17)O]cinnamoyl-chymotrypsin, and trans-p-methoxy-[(17)O]cinnamoyl-chymotrypsin. We show that both the (17)O chemical shifts and nuclear quadrupolar parameters obtained for these acyl-enzyme intermediates in the solid state are correlated with their deacylation rate constants measured in aqueous solution. With the aid of quantum mechanical calculations, the experimental (17)O NMR parameters were interpreted as to reflect the hydrogen bonding interactions between the carbonyl (C═(17)O) functional group of the acyl moiety and the two NH groups from the protein backbone (Ser195 and Gly193) in the oxyanion hole, a general feature of all serine proteases. Our results further suggest that the (17)O chemical shift and quadrupole coupling constant display distinctly different sensitivities toward...
Solid state nuclear magnetic resonance, Jan 27, 2016
We report synthesis and solid-state (17)O NMR characterization of four site-specifically (17)O-la... more We report synthesis and solid-state (17)O NMR characterization of four site-specifically (17)O-labeled 2-acylbenzoic acids (2-RC(O)C6H4COOH) where R=H and CH3): 2-[3-(17)O]formylbenzoic acid, 2-[1,2-(17)O2]formylbenzoic acid, 2-[3-(17)O]acetylbenzoic acid, and 2-[1,2,3-(17)O3]acetylbenzoic acid. In the solid state, both 2-formyl- and 2-acetyl-benzoic acids exist as the cyclic phthalide form each containing a five-membered lactone ring and a cyclic hemiacetal/hemiketal group. Static and magic-angle-spinning (17)O NMR spectra were recorded at 14.1 and 21.1T for these compounds, from which the (17)O chemical shift and nuclear quadrupolar coupling tensors were determined for each oxygen site. These results represent the first time that (17)O NMR tensors are fully characterized for lactone, cyclic hemiacetal, and cyclic hemiketal functional groups. We also report solid-state (17)O NMR data for the cyclic hemiketal group an anticoagulant drug, warfarin. Experimental (17)O NMR tensors in t...
Angewandte Chemie (International ed. in English), Jan 22, 2017
While NMR and IR spectroscopic signatures and structural characteristics of low-barrier hydrogen ... more While NMR and IR spectroscopic signatures and structural characteristics of low-barrier hydrogen bond (LBHB) formation are well documented in the literature, direct measurement of the LBHB energy is difficult. Here, we show that solid-state (17) O NMR spectroscopy can provide unique information about the energy required to break a LBHB. Our solid-state (17) O NMR data show that the HB enthalpy of the O⋅⋅⋅H⋅⋅⋅N LBHB formed in crystalline nicotinic acid is only 7.7±0.5 kcal mol(-1) , suggesting that not all LBHBs are particularly strong.
The journal of physical chemistry. B, Nov 17, 2016
We report a combined solid-state ((1)H, (2)H, (13)C, (17)O) NMR and plane-wave density functional... more We report a combined solid-state ((1)H, (2)H, (13)C, (17)O) NMR and plane-wave density functional theory (DFT) computational study of the O···H···O low-barrier hydrogen bonds (LBHBs) in two 1,3-diketone compounds: dibenzoylmethane (1) and curcumin (2). In the solid state, both 1 and 2 exist in the cis-keto-enol tautomeric form, each exhibiting an intramolecular LBHB with a short O···O distance (2.435 Å in 1 and 2.455 Å in 2). Whereas numerous experimental (structural and spectroscopic) and computational studies have been reported for the enol isomers of 1,3-diketones, a unified picture about the proton location within an LBHB is still lacking. This work reports for the first time the solid-state (17)O NMR data for the O···H···O LBHBs in 1,3-diketones. The central conclusion of this work is that detailed information about the probability density distribution of the proton (nuclear zero-point motion) across an LBHB can be obtained from a combination of solid-state NMR and plane-wave D...