Chemistry of the new immunosuppressant KH-1060: new synthons and x-ray evidence for unique side-chain geometry

The syntheses of new BEDT-TTF derivatives are described. These comprise BEDT-TTF with one ethynyl group (HC≡C-), with two (n-heptyl) or four (n-butyl) alkyl side chains, with two trans acetal (-CH(OMe)2) groups, with two trans aminomethyl (-CH2NH2) groups, and with an iminodiacetate (-CH2N(CH2CO2−)2 side chain. Three transition metal salts have been prepared from the latter donor, and their magnetic properties are reported. Three tris-donor systems are reported bearing three BEDT-TTF derivatives with ester links to a core derived from benzene-1,3,5-tricarboxylic acid. The stereochemistry and molecular structure of the donors are discussed. X-ray crystal structures of two BEDT-TTF donors are reported: one with two CH(OMe)2 groups and with one a -CH2N(CH2CO2Me)2 side chain.

Download Full-text

Arsenoplatin-Ferritin Nanocage: Structure and Cytotoxicity

International Journal of Molecular Sciences ◽

10.3390/ijms22041874 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1874

Author(s):

Giarita Ferraro ◽

Alessandro Pratesi ◽

Damiano Cirri ◽

Paola Imbimbo ◽

Daria Maria Monti ◽

...

Keyword(s):

Biological Activity ◽

Diffraction Data ◽

Inductively Coupled Plasma ◽

Emission Spectroscopy ◽

Atomic Emission ◽

Side Chain ◽

Plasma Atomic Emission ◽

Average Amount ◽

X Ray ◽

Inductively Coupled

Arsenoplatin-1 (AP-1), the prototype of a novel class of metallodrugs containing a PtAs(OH)2 core, was encapsulated within the apoferritin (AFt) nanocage. UV-Vis absorption spectroscopy and inductively coupled plasma-atomic emission spectroscopy measurements confirmed metallodrug encapsulation and allowed us to determine the average amount of AP-1 trapped inside the cage. The X-ray structure of AP-1-encapsulated AFt was solved at 1.50 Å. Diffraction data revealed that an AP-1 fragment coordinates the side chain of a His residue. The biological activity of AP-1-loaded AFt was comparatively tested on a few representative cancer and non-cancer cell lines. Even though the presence of the cage reduces the overall cytotoxicity of AP-1, it improves its selectivity towards cancer cells.

Download Full-text

Are mesoionic compounds aromatic?

Canadian Journal of Chemistry ◽

10.1139/v98-065 ◽

1998 ◽

Vol 76 (6) ◽

pp. 869-872 ◽

Cited By ~ 15

Author(s):

Alfredo Mayall Simas ◽

Joseph Miller ◽

Petrônio Filgueiras de Athayade Filho

Keyword(s):

Experimental Evidence ◽

Key Words ◽

Dipole Moments ◽

The Other ◽

Side Chain ◽

Theoretical Studies ◽

X Ray Diffraction ◽

Ring Plane ◽

X Ray ◽

Single Bonds

We have evaluated the experimental evidence relevant to the structure and character of mesoionic compounds, accumulated for more than 100 years and including X-ray diffraction studies. We have also evaluated relevant theoretical studies. All these, including our own extensive work, lead us to conclude that mesoionic compounds are not aromatic. According to our recent definition “mesoionic compounds are planar five-membered heterocyclic betaines with at least one side chain whose α-atom is also in the ring plane and with dipole moments of the order of 5 D. Electrons are delocalized over two regions separated by what are essentially single bonds. One region, which includes the a-atom of the side chain is associated with the HOMO and negative π-charge whereas the other is associated with the LUMO and positive π-charge.” Key words: mesoionic compounds, betaines, aromaticity.

Download Full-text

X-ray powder diffraction data for ertapenem side chain, C20H19N3O7S

Powder Diffraction ◽

10.1017/s0885715617000513 ◽

2017 ◽

Vol 32 (3) ◽

pp. 203-205

Author(s):

Xiang Lin ◽

Wei Ling Zhuo ◽

Qiao Hong Du ◽

Xi Lin Peng ◽

Hui Li

Keyword(s):

Powder Diffraction ◽

Diffraction Data ◽

Unit Cell Volume ◽

Unit Cell ◽

Side Chain ◽

Powder Diffraction Data ◽

Unit Cell Parameters ◽

Space Group ◽

X Ray ◽

Cell Parameters

X-ray powder diffraction data, unit-cell parameters, and space group for ertapenem side chain, C20H19N3O7S, are reported [a = 4.907(6) Å, b = 18.686(3) Å, c = 22.071(1) Å, α = γ = 90°, β = 90.759(5)°, unit-cell volume V = 2023.82 Å3, Z = 4, ρcal = 1.462 g cm−3, and space group P21/c]. All measured lines were indexed and are consistent with the P21/c space group. No detectable impurity was observed.

Download Full-text

Enzymatic β-Oxidation of the Cholesterol Side Chain in Mycobacterium Tuberculosis Bifurcates Stereospecifically at Hydration of 3-Oxo-Cholest-4,22- Dien-24-Oyl-CoA

10.26434/chemrxiv.13728112 ◽

2021 ◽

Author(s):

Tianao Yuan ◽

Joshua Werman ◽

Xingyu Yin ◽

Meng Yang ◽

Miguel Garcia-Diaz ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Fatty Acid ◽

Alcohol Dehydrogenase ◽

Side Chain ◽

Crystallographic Structure ◽

X Ray ◽

Steroid Substrate ◽

Unique Ability ◽

Therapeutics Development ◽

Chain Type

The unique ability of Mycobacterium tuberculosis (Mtb) to utilize host lipids such as cholesterol for survival, persistence, and virulence has made the metabolic pathway of cholesterol an area of great interest for therapeutics development, and bioproduction of valuable sterol intermediates. Herein, we identify and characterize two genes from the <a></a><a>Cho-region of the Mtb genome</a>, chsH3 (Rv3538) and chsB1 (Rv3502c). Their protein products catalyze <a></a><a>two sequential stereospecific</a>hydration and dehydrogenation steps in the b-oxidation of the cholesterol side chain. ChsH3 favors the 22S hydration of 3-oxo-cholest-4,22-dien-24-oyl-CoA in contrast to the previously reported EchA19 (Rv3516) which catalyzes formation of the (22R)-hydroxy-3-oxo-cholest-4-en-24-oyl-CoA from the same enoyl-CoA substrate. ChsB1 is stereospecific and catalyzes dehydrogenation of the ChsH3 product, but not the EchA19 product. The X-ray crystallographic structure of the ChsB1 apo-protein was determined at a resolution of 2.03 Å and the holo-enzyme with bound NAD+ cofactor at 2.21 Å.The homodimeric structure is representative of a classical NAD+ utilizing short-chain type alcohol dehydrogenase/reductase, including a Rossmann-fold motif, but exhibits a unique substrate binding site architecture that is of greater length and width than its homologous counterparts, likely to accommodate the bulky steroid substrate. Intriguingly, Mtb utilizes MaoC-like hydratases in sterol side-chain catabolism in contrast to fatty acid b-oxidation in other species that utilize the evolutionarily distinct crotonase family of hydratases.

Download Full-text

NMR and X-ray studies of apetalic acid isolated from Calophyllum brasiliense and of its chiral amides

Canadian Journal of Chemistry ◽

10.1139/cjc-2021-0163 ◽

2021 ◽

Author(s):

Marie-Rose Van Calsteren ◽

Ricardo Reyes-Chilpa ◽

Chistopher K Jankowski ◽

Fleur Gagnon ◽

Simón Hernández-Ortega ◽

...

Keyword(s):

Antimycobacterial Activity ◽

Side Chain ◽

Carboxyl Group ◽

X Ray Diffraction ◽

Rain Forests ◽

X Ray ◽

X Ray Crystallography ◽

Calophyllum Brasiliense ◽

Derivatives Of

The tropical tree Calophyllum brasiliense (Clusiaceae) grows in the rain forests from Brazil to Mexico. Its leaves, as well as those of other Calophyllum species, are rich sources of chromanone acids, such as apetalic acid, isoapetalic acid, and their derivatives. Apetalic acid has shown significant antimycobacterial activity. The biological activity of apetalic acid has been related to the configuration of three asymmetric centers and the stereochemistry of the molecule; however, the C-19 configuration in the acidic side chain has not been fully resolved. For this reason, the unequivocal determination of the absolute configuration by means of X-ray crystallography in a sample of unique homogeneous apetalic acid stereoisomer was the most important point to start this study. We prepared some chiral amides using the carboxyl group. We determined the C-19 stereochemistry of apetalic acid, and its specific chiral derivatives, using NMR, X-ray diffraction methods, and molecular mechanics. Finally, we observed that steric hindrance in the side chain of apetalic acid leads to restriction of rotation around the pivotal link C-10 and C-19 establishing chiral centers at C2(R), C3(S), and C19(R). We were able to separate derivatives of these two high-rotatory-barrier conformers of apetalic acid by forming diastereoisomeric amides with phenylglycine methyl ester having a chiral center at C-2’. Our results allowed the conclusion of the existence of atropisomerism in the apetalic acid molecule.

Download Full-text

X-ray study of bilayered tilted structures in liquid crystalline side chain methacrylic polymers

Liquid Crystals ◽

10.1080/0267829031000091129 ◽

2003 ◽

Vol 30 (5) ◽

pp. 585-589 ◽

Cited By ~ 4

Author(s):

Eduardo A. Soto-Bustamante ◽

Rafael Vergara-Toloza ◽

Danilo Saldaño-Hurtado ◽

Patricio Navarrete-Encina

Keyword(s):

Liquid Crystalline ◽

Side Chain ◽

X Ray

Download Full-text

X-ray investigations of Langmuir-Blodgett multilayer films of side-chain liquid crystal copolymers

Liquid Crystals ◽

10.1080/02678299408027857 ◽

1994 ◽

Vol 16 (5) ◽

pp. 869-875 ◽

Cited By ~ 14

Author(s):

R. Geer ◽

S. Qadri ◽

R. Shashidhar ◽

A. F. Thibodeaux ◽

R. S. Duran

Keyword(s):

Liquid Crystal ◽

Multilayer Films ◽

Side Chain ◽

X Ray ◽

Langmuir Blodgett

Download Full-text

Discovery of Stealthin Derivatives and Implication of the Amidotransferase FlsN3 in the Biosynthesis of Nitrogen-Containing Fluostatins

Marine Drugs ◽

10.3390/md17030150 ◽

2019 ◽

Vol 17 (3) ◽

pp. 150 ◽

Cited By ~ 2

Author(s):

Chunshuai Huang ◽

Chunfang Yang ◽

Zhuangjie Fang ◽

Liping Zhang ◽

Wenjun Zhang ◽

...

Keyword(s):

Spectroscopic Data ◽

Bioinformatics Analysis ◽

Biological Activities ◽

Side Chain ◽

X Ray Diffraction ◽

X Ray ◽

Aromatic Polyketides ◽

Plausible Mechanism ◽

Encoding Gene

Diazobenzofluorene-containing atypical angucyclines exhibit promising biological activities. Here we report the inactivation of an amidotransferase-encoding gene flsN3 in Micromonospora rosaria SCSIO N160, a producer of fluostatins. Bioinformatics analysis indicated that FlsN3 was involved in the diazo formation. Chemical investigation of the flsN3-inactivation mutant resulted in the isolation of a variety of angucycline aromatic polyketides, including four racemic aminobenzo[b]fluorenes stealthins D–G (9–12) harboring a stealthin C-like core skeleton with an acetone or butanone-like side chain. Their structures were elucidated on the basis of nuclear magnetic resonance (NMR) spectroscopic data and X-ray diffraction analysis. A plausible mechanism for the formation of stealthins D–G (9–12) was proposed. These results suggested a functional role of FlsN3 in the formation/modification of N–N bond-containing fluostatins.

Download Full-text