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.
The crystal and molecular structure of rotenone, a naturally occurring insecticide with mitochond... more The crystal and molecular structure of rotenone, a naturally occurring insecticide with mitochondrial and mitotic spindle inhibitory properties, was determined by direct methods. The crystals were orthorhombic, space group, P2,2,2, with two molecules in the asymmetric unit; a = 8.413 (1) A, b = 19.840(l), c = 23.581(l), V = 3936 A3, Z = 8. The structure was refined by least-squares methods to a final R = 0.067. The two molecules in the asymmetric unit have different conformations about the junction between the nonaromatic rings B and C. Ring B is in a sofa conformation in both molecules, with a slight distortion toward a halfchair in I, but with C8 and C8' on opposite sides of the planar part of the rings. This difference in conformation results in I having an extended (linear) shape while II is Vshaped. The more elongated conformation of the molecule (I) has not been reported in previous studies. Ring C also has opposite conformations in the two molecules. The angle between the planes formed by rings A and D in molecule I is 64.3", while in molecule II it is 88.3". Molecular mechanics techniques were used to determine the energy of the two conformations. These calculations, at room temperature, predict molecule II to be the more stable conformer. The highly flexible site in the B/C ring junction is also chemically very reactive. This flexibility and reactivity are further discussed in terms of rotenone's inhibitory activities. Q 1988 Academic Press. Inc.
Previous studies established some Ti compounds as having marked activity against tumors of the ga... more Previous studies established some Ti compounds as having marked activity against tumors of the gastrointestinal tract and lack of side effects common to widely used cytostatic agents. We describe pertinent structural features of known antitumor Ti agents and other potentially active compounds. Particularly noteworthy features are that Ti-O bonds are short and Ti-O-Ti bond angles are large, demonstrating that in these compounds the O binding has high s-character approaching sp hybridization. /'he successful drug development/1/of the antitumor agent cis-diaminodichloroplatinum(II) (cisplatin) 1, generated a search for other active metal compounds and cis-diethoxy-bis(1-phenylbutane-l,3dionato)titanium(IV), [(bzac)2Ti(OEt)2] (budotitane) 2, was the first non-Pt metal antitumor compound that reached clinical trials /2/. The ligand 1-phenylbutane-l,3-dionato bzac benzoylacetonato, is an asymmetric [3-diketone chelator useful tbr establishing one key structural feature tbr activity in budotitane, namely, the existence of two OEt cis leaving groups, which arc analogous to the 2 CI in cisplatin. Another Ti antitumor agent is titanocene dichloride, (Cp)2TiCI2 3, Cp cyclopentadienyl, which possesses 2 CI leaving groups/5/. Among the differences between Ti antitumor drugs and cisplatin is the spectrum of activity, as Ti drugs operate against gastrointestinal tumors whereas Pt drugs do not. On the other hand, P338 and LI210 leukemia are sensitive targets for Pt drugs but not for budotitane/4/. Other differences include a much faster hydrolysis rate of the leaving groups in the former, and the environment where the metal-leaving group bonds cleave: outside the cell for Ti drugs and inside the cell tbr Pt drugs/1/. Titanocenc dichloride shows a larger spectrum of activity compared to budotitane. This is likely due to better solubility in physiological medium and it is currently in phase II clinical tests /5/, whereas the Structural Features of Antitumor Titanium. Agents and Related Compounds development of budotitane is limited by formulation problems /6/. Titanocene dichloride interacts with transferrin, a protein associated with iron transport, and suggests a possible mode of entry into the tumor cell. That is, the protein, with a Ti atom bound to one of its 2 domains/7,8/, could cross the tumor cell wall, which is characterized by greater amount of transferrin receptors than present in normal cells, and allow metal interaction with unknown targets.
The mechanism by which the naturally occurring polyphenolic compounds resveratrol (RES), C 14 H 1... more The mechanism by which the naturally occurring polyphenolic compounds resveratrol (RES), C 14 H 12 O 3 , and its metabolite piceatannol (PIC), C 14 H 12 O 4 , scavenge free radicals is studied using experimental and density functional theory (DFT) methods. PIC's crystal structure shows a strong intermolecular hydrogen bond network, which, through a concerted motion of the hydroxyl hydrogen atoms, can produce a second hydrogen bond chain. This reorganization offers a low-energy pathway for the transfer of hydrogen atoms and is a contributing factor to PIC's biological activity. Additionally, DFT calculations describing the entire reaction mechanism of RES, PIC, and 3,3′,4′,5,5′-pentahydroxystilbene with hydroxyl and peroxyl radicals agree with experimental results, showing that increased hydroxylation aids in scavenging activity. PIC is more efficient than RES because (i) by sharing its 3′-OH hydrogen atom with its adjacent neighbor, O-4′, the abstraction and transfer of the 4′-H atom to the free radical becomes easier and (ii) the resulting PIC semiquinone radical is more stable. As a result of the reaction with OH • , both RES and PIC form water; with the peroxyl radical, both RES and PIC form hydrogen peroxide. Also, docking of PIC onto the protein transthyretin suggests better performance than RES and confirms its possible application in neurodegenerative conditions such as Alzheimer's disease.
The taurine amino-acid derivative, taurolidine, bis-(1,1-dioxoperhydro-1,2,4-thiabiazinyl-4)metha... more The taurine amino-acid derivative, taurolidine, bis-(1,1-dioxoperhydro-1,2,4-thiabiazinyl-4)methane, shows broad antibacterial action against gram-positive and gram-negative bacteria, mycobacteria and some clinically relevant fungi. It inhibits, in vitro, the adherence of Escherichia coli and Staphylococcus aureus to human epithelial and fibroblast cells. Taurolidine is unstable in aqueous solution and breaks down into derivatives which are thought to be responsible for the biological activity. To understand the taurolidine antibacterial mechanism of action, we provide the experimental single crystal X-ray diffraction results together with theoretical methods to characterize the hydrolysis/decomposition reactions of taurolidine. The crystal structure features two independent molecules linked through intermolecular H-bonds with one of them somewhat positively charged. Taurolidine in a biological environment exists in equilibrium with taurultam derivatives and this is described theoretically as a 2-step process without an energy barrier: formation of cationic taurolidine followed by a nucleophilic attack of O(hydroxyl) on the exocyclic C(methylene). A concerted mechanism describes the further hydrolysis of the taurolidine derivative methylol-taurultam. The interaction of methylol-taurultam with the diaminopimelic NH 2 group in the E. coli bacteria cell wall (peptidoglycan) has a negative DG value (238.2 kcal/mol) but a high energy barrier (45.8 kcal/ mol) suggesting no reactivity. On the contrary, taurolidine docking into E. coli fimbriae protein, responsible for bacteria adhesion to the bladder epithelium, shows it has higher affinity than mannose (the natural substrate), whereas methyloltaurultam and taurultam are less tightly bound. Since taurolidine is readily available because it is administered in high doses after peritonitis surgery, it may successfully compete with mannose explaining its effectiveness against bacterial infections at laparoscopic lesions.
The in vitro antiproliferative activity of the title compound on five tumor cell lines shows pref... more The in vitro antiproliferative activity of the title compound on five tumor cell lines shows preference for the colon−rectal tumor HCT116, IC 50 = 13.98 μM, followed by breast MCF7 (19.58 μM) and ovarian A2780 (23.38 μM) cell lines; human glioblastoma U-87 and lung carcinoma A549 are less sensitive. A commercial curcumin reagent, also containing demethoxy and bis-demethoxy curcumin, was used to synthesize the title compound, and so (p-cymene)Ru(demethoxycurcuminato)chloro was also isolated and chemically characterized. The crystal structure of the title compound shows (1) the chlorine atom linking two neighboring complexes through H-bonds with two O-(hydroxyl), forming an infinite two-step network; (2) significant twist in the curcuminato, 20°between the planes of the two phenyl rings. This was also seen in the docking of the Ru-complex onto a rich guanine B-DNA decamer, where a Ru−N7(guanine) interaction is detected. This Ru−N7(guanine) interaction is also seen with ESI-MS on a Rucomplex-guanosine derivative.
A Density Functional Theory (DFT) analysis of the mixed phosphine complexes Au(PPh 3 )(Ph 2 P(CH ... more A Density Functional Theory (DFT) analysis of the mixed phosphine complexes Au(PPh 3 )(Ph 2 P(CH 2 ) 3 PPh 2 )X shows a clear trend in the metal geometry as the anion X -is varied: the softer the anion, the more it is tetrahedral, or alternatively, the more ionic the complex, the more the complex geometry approaches trigonal planar. A strong (soft) donor as cyanide (X -= CN -) penetrates markedly the coordination sphere and establishes the most tetrahedral geometry. In the antitumor compound Au(PPh 3 )(Ph 2 P(CH 2 ) 3 PPh 2 )Cl (X - = Cl -), the weaker donor chloride is slightly displaced from the coordination sphere with consequent strengthening of Au-P bonds, thus stabilizing a more pyramidal geometry. If the anion is completely out of the coordination sphere, the cation [Au(PPh 3 )(Ph 2 P(CH 2 ) 3 PPh 2 )] + shows further strengthening of Au-P bonds and a geometry very close to the trigonal planar "AuP 3 " system. X-ray and DFT data for Au(PPh 3 )(Ph 2 P(CH 2 ) 3 PPh 2 )Cl show generally good agreement; however, in the crystal the Au-Cl bond appears lengthened with consequent strong Au-P bonds. This is probably due to packing effects; nevertheless, the X-ray structure agrees with the trend mentioned above as well.
Thirteen new N-1',N-3'-disubstituted-2'H,3H,5'H-spiro-(2-benzofuran-1,4'-imid... more Thirteen new N-1',N-3'-disubstituted-2'H,3H,5'H-spiro-(2-benzofuran-1,4'-imidazolidine)-2',3,5'-triones were synthesized and their pharmacological activity determined with the objective to better understand their SAR for anticonvulsant activity. The anticonvulsant effects of these compounds were evaluated by standard pentylenetetrazol (scPTZ test) and maximum electroshock seizure (MES test) models in mice. Most of the compounds showed ability to protect against the pentylenetetrazol-induced convulsions. Compound 3o (the N-1'-p-nitrophenyl, N-3'-ethyl derivative) in the N-1'-aryl, N-3'-alkyl disubstituted series exhibited maximum activity with ED(50) of 41.8 mg/kg in scPTZ convulsion model.
Synthesis, Structure, and Sweetness of 4-Chloro-4-deoxy-α-Dgalactopyranosyl 1,4,6-Trichloro-1,4,6... more Synthesis, Structure, and Sweetness of 4-Chloro-4-deoxy-α-Dgalactopyranosyl 1,4,6-Trichloro-1,4,6-trideoxy-β-D-tagatofuranoside.-The reaction of 6-O-acetylsucrose with sulfuryl chloride in pyridine and dry chloroform at-60 • C according to the method of Lee is reinvestigated. Two products are identical to those reported earlier but one tetrachloro derivative is not a sorbofuranoside as reported, but the title compound (I). A comparison of the sweetness of the free deacetylated derivative with that of its 4'-chloro analogue clearly suggests that the halogen substituent at C-4' and its stereochemistry play a very important role in the sweetness of these compounds which has a relative ratio of 1:10.-(LEE, C. KUAN; KANG, H.
Journal of the American Chemical Society, Mar 1, 1978
Die Oxidation von Tetrathiafulvalen (TTF) mit HgCl2 in Acetonitril liefert neben Hg2Cl2 den Titel... more Die Oxidation von Tetrathiafulvalen (TTF) mit HgCl2 in Acetonitril liefert neben Hg2Cl2 den Titelkomplex, ein Trichloromercurat-(II)-Salz des TTF-Kationradikals.
Clovamide (trans-clovamide, (2S)-3-(3,4-dihydroxyphenyl)-2-[[(E)-3-(3,4-dihydroxyphenyl)prop-2-en... more Clovamide (trans-clovamide, (2S)-3-(3,4-dihydroxyphenyl)-2-[[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl] amino]propanoic acid) is a naturally occurring caffeoyl conjugate and a potent antioxidant found in the phenolic fraction of Theobroma Cacao L. beans. This work quantified clovamide content in single-origin cocoa beans at different production stages (raw, roasted, and winnowed side and end products) by high-performance liquid chromatography with diode array detector (HPLC-DAD). We analyzed the antioxidant activities of clovamide and these extracts by measuring their superoxide radical scavenging capabilities in a Rotating Ring-Disk Electrode (RRDE) electrochemical system against in-situ generated superoxide radical. Our studies concluded a positive correlation between clovamide concentration and the overall antioxidant activities of beans, with the roasting step showing a reduction effect on both. The subsequent refining steps recover the clovamide concentration. Antioxidant studies on clovamide alone by RRDE and density functional theory (DFT) studies led to the conclusion that it is a powerful oxygen radical scavenger, partially contributed by its molecular catechol moieties.
The nonbonded sulfur-sulfur distances are summarized in Table VII. The average intraligand "bite"... more The nonbonded sulfur-sulfur distances are summarized in Table VII. The average intraligand "bite" distance is 2.97 A, which is longer than the "bite" distance in many metal-1,l-dithiolato complexes39 yet shorter than the s-S van der Waals contact distance of 3.4 A.40 The three sulfur atoms, S(a), covalently bonded to the phosphorus atom form a triangle with nonbonded ed e distances in the range 3.067-3.138 sulfur atoms, S(p), form a triangle with nonbonded edge distances in the ranges 4.642-4.941 8, in 4.735-5.014 A in B. The two triangles are rotated by about 45" in each molecule and the triangular S3 planes are out of parallel by 2.9" in A and 4.0' in B. The overall distortions in the PS6 coordination polyhedron away from octahedral symmetry are indicated by the unequal P-S bond distances, the S-P-S and dithiocarbamate ligand bond angles, the trigonal S3 face twist, and the large volume of coordination space between the S (@) atoms. These distortions appear to result from a combination of steric constraints imposed by the tris(dithi0carbamate) chelate structure and a balance of covalent and ionic P-S electrostatic attractions. Nonbonded S-S and S-P lone-pair van der Waals repulsions also play some role in determining the final configuration. The geometry of the individual dithiocarbamate ligands is also of interest. The average S(a)-C distance, 1.763 A, is significantly longer than the average S(p)-C distance, 1.666 in A and 3.083-3.131 x in B. The three ionically associated 19, 3604-3608 A, and a comparable effect is also observed in the arsenic complex: S(a)-C = 1.760 8, and S(/3)-C = 1.678 A. The average C-N bond distance, 1.33 A, is comparable with those of most 1,l-dithiolato c o m p l e~e s .~~,~~ The two sulfur atoms, two nitrogen atoms, and three carbon atoms of each ligand form a plane which contains the central phosphorus atom. The equations for these planes and the atom deviations from the planes are summarized in Table VIII. The small distortions from planarity are likely a result of crystal-packing forces. The angles between the three ligand propeller blades, 78.2, 85.9, and 89.9" in A and 79.3, 85.6, and 87.3" in B, deviate from the 90' angle expected for an octahedral complex. Planes calculated for the CS2 and NC2 portions of each chelate ring show very small torsion angles in the S2C-NC2 linkage, Acknowledgment. The authors wish to recognize NSF Grants CHE-7802921 and MPS75-06111, which facilitated the purchases of the X-ray diffractometer and the NMR data system. R.T.P. wishes to acknowledge partial support of this work by the UNM Research Allocations Committee.
Full-matrix leastsquares refinement (nonhydrogen atoms anisotropic, H atoms isotropic) based on 1... more Full-matrix leastsquares refinement (nonhydrogen atoms anisotropic, H atoms isotropic) based on 1191 counter-collected Fo'S
The crystal and molecular structure of rotenone, a naturally occurring insecticide with mitochond... more The crystal and molecular structure of rotenone, a naturally occurring insecticide with mitochondrial and mitotic spindle inhibitory properties, was determined by direct methods. The crystals were orthorhombic, space group, P2,2,2, with two molecules in the asymmetric unit; a = 8.413 (1) A, b = 19.840(l), c = 23.581(l), V = 3936 A3, Z = 8. The structure was refined by least-squares methods to a final R = 0.067. The two molecules in the asymmetric unit have different conformations about the junction between the nonaromatic rings B and C. Ring B is in a sofa conformation in both molecules, with a slight distortion toward a halfchair in I, but with C8 and C8' on opposite sides of the planar part of the rings. This difference in conformation results in I having an extended (linear) shape while II is Vshaped. The more elongated conformation of the molecule (I) has not been reported in previous studies. Ring C also has opposite conformations in the two molecules. The angle between the planes formed by rings A and D in molecule I is 64.3", while in molecule II it is 88.3". Molecular mechanics techniques were used to determine the energy of the two conformations. These calculations, at room temperature, predict molecule II to be the more stable conformer. The highly flexible site in the B/C ring junction is also chemically very reactive. This flexibility and reactivity are further discussed in terms of rotenone's inhibitory activities. Q 1988 Academic Press. Inc.
The relationship between oxidative stress and inflammation is well known, and exogenous antioxida... more The relationship between oxidative stress and inflammation is well known, and exogenous antioxidants, primarily phytochemical natural products, may assist the body’s endogenous defense systems in preventing diseases due to excessive inflammation. In this study, we evaluated the antioxidant properties of ethnomedicines from Peru that exhibit anti-inflammatory activity by measuring the superoxide scavenging activity of ethanol extracts of Maytenus octogona aerial parts using hydrodynamic voltammetry at a rotating ring-disk electrode (RRDE). The chemical compositions of these extracts are known and the interactions of three methide-quinone compounds found in Maytenus octogona with caspase-1 were analyzed using computational docking studies. Caspase-1 is a critical enzyme triggered during the activation of the inflammasome and its actions are associated with excessive release of cytokines. The most important amino acid involved in active site caspase-1 inhibition is Arg341 and, through ...
The crystal and molecular structures of two isomeric inhibitors of carcinogenesis by certain poly... more The crystal and molecular structures of two isomeric inhibitors of carcinogenesis by certain polycyclic aromatic hydrocarbons are described. The two compounds are 7,8-benzoflavone and 5,6-benzoflavone, which are shown by X-ray crystallographic studies to differ appreciably in their three-dimensional structures. Polycyclic aromatic hydrocarbons are metabolically activated by an enzyme system that is responsibe for the detoxification of many chemicals that enter the body. The two benzoflavones described here differ in their effect towards specific enzymes in the metabolizing system. Potential energy calculations predict that a nonplanar conformation is most probable for these flavone derivatives, as a result of the presence of a biphenyl-like system. Such a conformation is found for 7,8-benzoflavone with a torsion angle of 23 degrees between the phenyl group and the rest of the molecule. The isomeric 5,6-benzoflavone is, in contrast, found to be a predominantly flat molecule. There is...
ChemInform Abstract Der Titelkomplex (I) wurde nach einer Literatunnethode dargestellt. Er ist mi... more ChemInform Abstract Der Titelkomplex (I) wurde nach einer Literatunnethode dargestellt. Er ist mit der dreizähnigen Schiffschen Base und dem N-Atom in 7-Stellung des Theophyllins quadratisch-planar koordiniert. Zu dem O-Atom in 6-Stellung bestehen nur schwache echselwirkungen. Umkristallisation aus MeOH lieferte das 3.5-Hydrat, aus Wasser das Trihydrat und aus 95%igem EtOH das Monohydrat, die alle mit acht Molekülen pro Elementarzelle aber in verschiedenen Raumgruppen kristallisieren, das 3.S-Hydrat in Pnna, das Trihydrat in P2/ c und das Monohydrat in Pbcm.
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.
The crystal and molecular structure of rotenone, a naturally occurring insecticide with mitochond... more The crystal and molecular structure of rotenone, a naturally occurring insecticide with mitochondrial and mitotic spindle inhibitory properties, was determined by direct methods. The crystals were orthorhombic, space group, P2,2,2, with two molecules in the asymmetric unit; a = 8.413 (1) A, b = 19.840(l), c = 23.581(l), V = 3936 A3, Z = 8. The structure was refined by least-squares methods to a final R = 0.067. The two molecules in the asymmetric unit have different conformations about the junction between the nonaromatic rings B and C. Ring B is in a sofa conformation in both molecules, with a slight distortion toward a halfchair in I, but with C8 and C8' on opposite sides of the planar part of the rings. This difference in conformation results in I having an extended (linear) shape while II is Vshaped. The more elongated conformation of the molecule (I) has not been reported in previous studies. Ring C also has opposite conformations in the two molecules. The angle between the planes formed by rings A and D in molecule I is 64.3", while in molecule II it is 88.3". Molecular mechanics techniques were used to determine the energy of the two conformations. These calculations, at room temperature, predict molecule II to be the more stable conformer. The highly flexible site in the B/C ring junction is also chemically very reactive. This flexibility and reactivity are further discussed in terms of rotenone's inhibitory activities. Q 1988 Academic Press. Inc.
Previous studies established some Ti compounds as having marked activity against tumors of the ga... more Previous studies established some Ti compounds as having marked activity against tumors of the gastrointestinal tract and lack of side effects common to widely used cytostatic agents. We describe pertinent structural features of known antitumor Ti agents and other potentially active compounds. Particularly noteworthy features are that Ti-O bonds are short and Ti-O-Ti bond angles are large, demonstrating that in these compounds the O binding has high s-character approaching sp hybridization. /'he successful drug development/1/of the antitumor agent cis-diaminodichloroplatinum(II) (cisplatin) 1, generated a search for other active metal compounds and cis-diethoxy-bis(1-phenylbutane-l,3dionato)titanium(IV), [(bzac)2Ti(OEt)2] (budotitane) 2, was the first non-Pt metal antitumor compound that reached clinical trials /2/. The ligand 1-phenylbutane-l,3-dionato bzac benzoylacetonato, is an asymmetric [3-diketone chelator useful tbr establishing one key structural feature tbr activity in budotitane, namely, the existence of two OEt cis leaving groups, which arc analogous to the 2 CI in cisplatin. Another Ti antitumor agent is titanocene dichloride, (Cp)2TiCI2 3, Cp cyclopentadienyl, which possesses 2 CI leaving groups/5/. Among the differences between Ti antitumor drugs and cisplatin is the spectrum of activity, as Ti drugs operate against gastrointestinal tumors whereas Pt drugs do not. On the other hand, P338 and LI210 leukemia are sensitive targets for Pt drugs but not for budotitane/4/. Other differences include a much faster hydrolysis rate of the leaving groups in the former, and the environment where the metal-leaving group bonds cleave: outside the cell for Ti drugs and inside the cell tbr Pt drugs/1/. Titanocenc dichloride shows a larger spectrum of activity compared to budotitane. This is likely due to better solubility in physiological medium and it is currently in phase II clinical tests /5/, whereas the Structural Features of Antitumor Titanium. Agents and Related Compounds development of budotitane is limited by formulation problems /6/. Titanocene dichloride interacts with transferrin, a protein associated with iron transport, and suggests a possible mode of entry into the tumor cell. That is, the protein, with a Ti atom bound to one of its 2 domains/7,8/, could cross the tumor cell wall, which is characterized by greater amount of transferrin receptors than present in normal cells, and allow metal interaction with unknown targets.
The mechanism by which the naturally occurring polyphenolic compounds resveratrol (RES), C 14 H 1... more The mechanism by which the naturally occurring polyphenolic compounds resveratrol (RES), C 14 H 12 O 3 , and its metabolite piceatannol (PIC), C 14 H 12 O 4 , scavenge free radicals is studied using experimental and density functional theory (DFT) methods. PIC's crystal structure shows a strong intermolecular hydrogen bond network, which, through a concerted motion of the hydroxyl hydrogen atoms, can produce a second hydrogen bond chain. This reorganization offers a low-energy pathway for the transfer of hydrogen atoms and is a contributing factor to PIC's biological activity. Additionally, DFT calculations describing the entire reaction mechanism of RES, PIC, and 3,3′,4′,5,5′-pentahydroxystilbene with hydroxyl and peroxyl radicals agree with experimental results, showing that increased hydroxylation aids in scavenging activity. PIC is more efficient than RES because (i) by sharing its 3′-OH hydrogen atom with its adjacent neighbor, O-4′, the abstraction and transfer of the 4′-H atom to the free radical becomes easier and (ii) the resulting PIC semiquinone radical is more stable. As a result of the reaction with OH • , both RES and PIC form water; with the peroxyl radical, both RES and PIC form hydrogen peroxide. Also, docking of PIC onto the protein transthyretin suggests better performance than RES and confirms its possible application in neurodegenerative conditions such as Alzheimer's disease.
The taurine amino-acid derivative, taurolidine, bis-(1,1-dioxoperhydro-1,2,4-thiabiazinyl-4)metha... more The taurine amino-acid derivative, taurolidine, bis-(1,1-dioxoperhydro-1,2,4-thiabiazinyl-4)methane, shows broad antibacterial action against gram-positive and gram-negative bacteria, mycobacteria and some clinically relevant fungi. It inhibits, in vitro, the adherence of Escherichia coli and Staphylococcus aureus to human epithelial and fibroblast cells. Taurolidine is unstable in aqueous solution and breaks down into derivatives which are thought to be responsible for the biological activity. To understand the taurolidine antibacterial mechanism of action, we provide the experimental single crystal X-ray diffraction results together with theoretical methods to characterize the hydrolysis/decomposition reactions of taurolidine. The crystal structure features two independent molecules linked through intermolecular H-bonds with one of them somewhat positively charged. Taurolidine in a biological environment exists in equilibrium with taurultam derivatives and this is described theoretically as a 2-step process without an energy barrier: formation of cationic taurolidine followed by a nucleophilic attack of O(hydroxyl) on the exocyclic C(methylene). A concerted mechanism describes the further hydrolysis of the taurolidine derivative methylol-taurultam. The interaction of methylol-taurultam with the diaminopimelic NH 2 group in the E. coli bacteria cell wall (peptidoglycan) has a negative DG value (238.2 kcal/mol) but a high energy barrier (45.8 kcal/ mol) suggesting no reactivity. On the contrary, taurolidine docking into E. coli fimbriae protein, responsible for bacteria adhesion to the bladder epithelium, shows it has higher affinity than mannose (the natural substrate), whereas methyloltaurultam and taurultam are less tightly bound. Since taurolidine is readily available because it is administered in high doses after peritonitis surgery, it may successfully compete with mannose explaining its effectiveness against bacterial infections at laparoscopic lesions.
The in vitro antiproliferative activity of the title compound on five tumor cell lines shows pref... more The in vitro antiproliferative activity of the title compound on five tumor cell lines shows preference for the colon−rectal tumor HCT116, IC 50 = 13.98 μM, followed by breast MCF7 (19.58 μM) and ovarian A2780 (23.38 μM) cell lines; human glioblastoma U-87 and lung carcinoma A549 are less sensitive. A commercial curcumin reagent, also containing demethoxy and bis-demethoxy curcumin, was used to synthesize the title compound, and so (p-cymene)Ru(demethoxycurcuminato)chloro was also isolated and chemically characterized. The crystal structure of the title compound shows (1) the chlorine atom linking two neighboring complexes through H-bonds with two O-(hydroxyl), forming an infinite two-step network; (2) significant twist in the curcuminato, 20°between the planes of the two phenyl rings. This was also seen in the docking of the Ru-complex onto a rich guanine B-DNA decamer, where a Ru−N7(guanine) interaction is detected. This Ru−N7(guanine) interaction is also seen with ESI-MS on a Rucomplex-guanosine derivative.
A Density Functional Theory (DFT) analysis of the mixed phosphine complexes Au(PPh 3 )(Ph 2 P(CH ... more A Density Functional Theory (DFT) analysis of the mixed phosphine complexes Au(PPh 3 )(Ph 2 P(CH 2 ) 3 PPh 2 )X shows a clear trend in the metal geometry as the anion X -is varied: the softer the anion, the more it is tetrahedral, or alternatively, the more ionic the complex, the more the complex geometry approaches trigonal planar. A strong (soft) donor as cyanide (X -= CN -) penetrates markedly the coordination sphere and establishes the most tetrahedral geometry. In the antitumor compound Au(PPh 3 )(Ph 2 P(CH 2 ) 3 PPh 2 )Cl (X - = Cl -), the weaker donor chloride is slightly displaced from the coordination sphere with consequent strengthening of Au-P bonds, thus stabilizing a more pyramidal geometry. If the anion is completely out of the coordination sphere, the cation [Au(PPh 3 )(Ph 2 P(CH 2 ) 3 PPh 2 )] + shows further strengthening of Au-P bonds and a geometry very close to the trigonal planar "AuP 3 " system. X-ray and DFT data for Au(PPh 3 )(Ph 2 P(CH 2 ) 3 PPh 2 )Cl show generally good agreement; however, in the crystal the Au-Cl bond appears lengthened with consequent strong Au-P bonds. This is probably due to packing effects; nevertheless, the X-ray structure agrees with the trend mentioned above as well.
Thirteen new N-1',N-3'-disubstituted-2'H,3H,5'H-spiro-(2-benzofuran-1,4'-imid... more Thirteen new N-1',N-3'-disubstituted-2'H,3H,5'H-spiro-(2-benzofuran-1,4'-imidazolidine)-2',3,5'-triones were synthesized and their pharmacological activity determined with the objective to better understand their SAR for anticonvulsant activity. The anticonvulsant effects of these compounds were evaluated by standard pentylenetetrazol (scPTZ test) and maximum electroshock seizure (MES test) models in mice. Most of the compounds showed ability to protect against the pentylenetetrazol-induced convulsions. Compound 3o (the N-1'-p-nitrophenyl, N-3'-ethyl derivative) in the N-1'-aryl, N-3'-alkyl disubstituted series exhibited maximum activity with ED(50) of 41.8 mg/kg in scPTZ convulsion model.
Synthesis, Structure, and Sweetness of 4-Chloro-4-deoxy-α-Dgalactopyranosyl 1,4,6-Trichloro-1,4,6... more Synthesis, Structure, and Sweetness of 4-Chloro-4-deoxy-α-Dgalactopyranosyl 1,4,6-Trichloro-1,4,6-trideoxy-β-D-tagatofuranoside.-The reaction of 6-O-acetylsucrose with sulfuryl chloride in pyridine and dry chloroform at-60 • C according to the method of Lee is reinvestigated. Two products are identical to those reported earlier but one tetrachloro derivative is not a sorbofuranoside as reported, but the title compound (I). A comparison of the sweetness of the free deacetylated derivative with that of its 4'-chloro analogue clearly suggests that the halogen substituent at C-4' and its stereochemistry play a very important role in the sweetness of these compounds which has a relative ratio of 1:10.-(LEE, C. KUAN; KANG, H.
Journal of the American Chemical Society, Mar 1, 1978
Die Oxidation von Tetrathiafulvalen (TTF) mit HgCl2 in Acetonitril liefert neben Hg2Cl2 den Titel... more Die Oxidation von Tetrathiafulvalen (TTF) mit HgCl2 in Acetonitril liefert neben Hg2Cl2 den Titelkomplex, ein Trichloromercurat-(II)-Salz des TTF-Kationradikals.
Clovamide (trans-clovamide, (2S)-3-(3,4-dihydroxyphenyl)-2-[[(E)-3-(3,4-dihydroxyphenyl)prop-2-en... more Clovamide (trans-clovamide, (2S)-3-(3,4-dihydroxyphenyl)-2-[[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl] amino]propanoic acid) is a naturally occurring caffeoyl conjugate and a potent antioxidant found in the phenolic fraction of Theobroma Cacao L. beans. This work quantified clovamide content in single-origin cocoa beans at different production stages (raw, roasted, and winnowed side and end products) by high-performance liquid chromatography with diode array detector (HPLC-DAD). We analyzed the antioxidant activities of clovamide and these extracts by measuring their superoxide radical scavenging capabilities in a Rotating Ring-Disk Electrode (RRDE) electrochemical system against in-situ generated superoxide radical. Our studies concluded a positive correlation between clovamide concentration and the overall antioxidant activities of beans, with the roasting step showing a reduction effect on both. The subsequent refining steps recover the clovamide concentration. Antioxidant studies on clovamide alone by RRDE and density functional theory (DFT) studies led to the conclusion that it is a powerful oxygen radical scavenger, partially contributed by its molecular catechol moieties.
The nonbonded sulfur-sulfur distances are summarized in Table VII. The average intraligand "bite"... more The nonbonded sulfur-sulfur distances are summarized in Table VII. The average intraligand "bite" distance is 2.97 A, which is longer than the "bite" distance in many metal-1,l-dithiolato complexes39 yet shorter than the s-S van der Waals contact distance of 3.4 A.40 The three sulfur atoms, S(a), covalently bonded to the phosphorus atom form a triangle with nonbonded ed e distances in the range 3.067-3.138 sulfur atoms, S(p), form a triangle with nonbonded edge distances in the ranges 4.642-4.941 8, in 4.735-5.014 A in B. The two triangles are rotated by about 45" in each molecule and the triangular S3 planes are out of parallel by 2.9" in A and 4.0' in B. The overall distortions in the PS6 coordination polyhedron away from octahedral symmetry are indicated by the unequal P-S bond distances, the S-P-S and dithiocarbamate ligand bond angles, the trigonal S3 face twist, and the large volume of coordination space between the S (@) atoms. These distortions appear to result from a combination of steric constraints imposed by the tris(dithi0carbamate) chelate structure and a balance of covalent and ionic P-S electrostatic attractions. Nonbonded S-S and S-P lone-pair van der Waals repulsions also play some role in determining the final configuration. The geometry of the individual dithiocarbamate ligands is also of interest. The average S(a)-C distance, 1.763 A, is significantly longer than the average S(p)-C distance, 1.666 in A and 3.083-3.131 x in B. The three ionically associated 19, 3604-3608 A, and a comparable effect is also observed in the arsenic complex: S(a)-C = 1.760 8, and S(/3)-C = 1.678 A. The average C-N bond distance, 1.33 A, is comparable with those of most 1,l-dithiolato c o m p l e~e s .~~,~~ The two sulfur atoms, two nitrogen atoms, and three carbon atoms of each ligand form a plane which contains the central phosphorus atom. The equations for these planes and the atom deviations from the planes are summarized in Table VIII. The small distortions from planarity are likely a result of crystal-packing forces. The angles between the three ligand propeller blades, 78.2, 85.9, and 89.9" in A and 79.3, 85.6, and 87.3" in B, deviate from the 90' angle expected for an octahedral complex. Planes calculated for the CS2 and NC2 portions of each chelate ring show very small torsion angles in the S2C-NC2 linkage, Acknowledgment. The authors wish to recognize NSF Grants CHE-7802921 and MPS75-06111, which facilitated the purchases of the X-ray diffractometer and the NMR data system. R.T.P. wishes to acknowledge partial support of this work by the UNM Research Allocations Committee.
Full-matrix leastsquares refinement (nonhydrogen atoms anisotropic, H atoms isotropic) based on 1... more Full-matrix leastsquares refinement (nonhydrogen atoms anisotropic, H atoms isotropic) based on 1191 counter-collected Fo'S
The crystal and molecular structure of rotenone, a naturally occurring insecticide with mitochond... more The crystal and molecular structure of rotenone, a naturally occurring insecticide with mitochondrial and mitotic spindle inhibitory properties, was determined by direct methods. The crystals were orthorhombic, space group, P2,2,2, with two molecules in the asymmetric unit; a = 8.413 (1) A, b = 19.840(l), c = 23.581(l), V = 3936 A3, Z = 8. The structure was refined by least-squares methods to a final R = 0.067. The two molecules in the asymmetric unit have different conformations about the junction between the nonaromatic rings B and C. Ring B is in a sofa conformation in both molecules, with a slight distortion toward a halfchair in I, but with C8 and C8' on opposite sides of the planar part of the rings. This difference in conformation results in I having an extended (linear) shape while II is Vshaped. The more elongated conformation of the molecule (I) has not been reported in previous studies. Ring C also has opposite conformations in the two molecules. The angle between the planes formed by rings A and D in molecule I is 64.3", while in molecule II it is 88.3". Molecular mechanics techniques were used to determine the energy of the two conformations. These calculations, at room temperature, predict molecule II to be the more stable conformer. The highly flexible site in the B/C ring junction is also chemically very reactive. This flexibility and reactivity are further discussed in terms of rotenone's inhibitory activities. Q 1988 Academic Press. Inc.
The relationship between oxidative stress and inflammation is well known, and exogenous antioxida... more The relationship between oxidative stress and inflammation is well known, and exogenous antioxidants, primarily phytochemical natural products, may assist the body’s endogenous defense systems in preventing diseases due to excessive inflammation. In this study, we evaluated the antioxidant properties of ethnomedicines from Peru that exhibit anti-inflammatory activity by measuring the superoxide scavenging activity of ethanol extracts of Maytenus octogona aerial parts using hydrodynamic voltammetry at a rotating ring-disk electrode (RRDE). The chemical compositions of these extracts are known and the interactions of three methide-quinone compounds found in Maytenus octogona with caspase-1 were analyzed using computational docking studies. Caspase-1 is a critical enzyme triggered during the activation of the inflammasome and its actions are associated with excessive release of cytokines. The most important amino acid involved in active site caspase-1 inhibition is Arg341 and, through ...
The crystal and molecular structures of two isomeric inhibitors of carcinogenesis by certain poly... more The crystal and molecular structures of two isomeric inhibitors of carcinogenesis by certain polycyclic aromatic hydrocarbons are described. The two compounds are 7,8-benzoflavone and 5,6-benzoflavone, which are shown by X-ray crystallographic studies to differ appreciably in their three-dimensional structures. Polycyclic aromatic hydrocarbons are metabolically activated by an enzyme system that is responsibe for the detoxification of many chemicals that enter the body. The two benzoflavones described here differ in their effect towards specific enzymes in the metabolizing system. Potential energy calculations predict that a nonplanar conformation is most probable for these flavone derivatives, as a result of the presence of a biphenyl-like system. Such a conformation is found for 7,8-benzoflavone with a torsion angle of 23 degrees between the phenyl group and the rest of the molecule. The isomeric 5,6-benzoflavone is, in contrast, found to be a predominantly flat molecule. There is...
ChemInform Abstract Der Titelkomplex (I) wurde nach einer Literatunnethode dargestellt. Er ist mi... more ChemInform Abstract Der Titelkomplex (I) wurde nach einer Literatunnethode dargestellt. Er ist mit der dreizähnigen Schiffschen Base und dem N-Atom in 7-Stellung des Theophyllins quadratisch-planar koordiniert. Zu dem O-Atom in 6-Stellung bestehen nur schwache echselwirkungen. Umkristallisation aus MeOH lieferte das 3.5-Hydrat, aus Wasser das Trihydrat und aus 95%igem EtOH das Monohydrat, die alle mit acht Molekülen pro Elementarzelle aber in verschiedenen Raumgruppen kristallisieren, das 3.S-Hydrat in Pnna, das Trihydrat in P2/ c und das Monohydrat in Pbcm.
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