Synthesis, characterization, molecular docking, and anticancer activities of new 1,3,4-oxadiazole-5-fluorocytosine hybrid derivatives.

Analogs of pyrimidine and 1,3,4-oxadiazole are two well established class of molecules proven as potent antiviral and anticancer agents in the pharmaceutical industry. We envisioned designing new molecules where these two heterocycles were conjugated with the goal of enhancing biological activity. In this vein, we synthesized a series of novel pyrimidine-1,3,4-oxadiazole conjugated hybrid molecules as potential anticancer and antiviral agents. Herein, we present a new design for 5-fluorocytosine-1,3,4-oxadiazole hybrids (5a-h) connected via a methylene bridge. An efficient synthesis of new derivatives was established, and all compounds were fully characterized by NMR and MS. Eight compounds were evaluated for their cytotoxic activity against fibrosarcoma (HT-1080), breast (MCF-7 and MDA-MB-231), lung carcinoma (A-549), and for their antiviral activity against SARS-CoV-2. Among all compounds tested, the compound 5e showed marked growth inhibition against all cell lines tested, particularly in HT-1080, with IC50 values of 19.56 µM. Meanwhile, all tested compounds showed no anti-SARS-CoV-2 activity, with EC50 >100 µM. The mechanism of cell death was investigated using Annexin V staining, caspase-3/7 activity, and analysis of cell cycle progression. The compound 5e induced apoptosis by the activation of caspase-3/7 and cell-cycle arrest in HT-1080 and A-549 cells at the G2M phase. The molecular docking suggested that the compound 5e activated caspase-3 via the formation of a stable complex protein-ligand.

Calcium trifluoroacetate as an efficient catalyst for ring-opening of epoxides by amines under solvent-free conditions.

Ca(CF3CO2)2 efficiently catalyzed the selective ring-opening of epoxides by amines leading to the synthesis of ß-aminoalcohols. The reaction works well with various aromatic and aliphatic amines under solvent-free conditions. Corresponding ß-aminoalcohols were obtained in excellent yields with high regioselectivity. The catalyst was easily prepared by reaction of CaH2 in trifluoroacetic acid.

(2Z,2'Z)-Diethyl 3,3'-[butane-1,4-diylbis(aza-nedi-yl)]bis-(but-2-enoate).

The whole mol-ecule of the title ß-enamino-ester, C(16)H(28)N(2)O(4), is generated by a crystallographic inversion center, situated at the mid-point of the central C-C bond of the 1,4-diamino-butane segment. There are two intra-molecular N-H⋯O hydrogen bonds that generate S(6) ring motifs. This leads to the Z conformation about the C=C bonds [1.3756 (17) Å]. The mol-ecule is S-shaped with the planar central 1,4-diamino-butane segment [maximum deviation for non H-atoms = 0.0058 (13) Å] being inclined to the ethyl butyl-enonate fragment [C-C-O-C-C=C-C; maximum deviation = 0.0710 (12) Å] by 15.56 (10)°. In the crystal, mol-ecules are linked via C-H⋯O inter-actions, leading to the formation of an undulating two-dimensional network lying parallel to the bc plane.

(R)-2-Methyl-5-[(R)-2,4,4,4-tetra-chloro-butan-2-yl]cyclo-hex-2-enone.

The title compound, C(11)H(14)Cl(4)O, was efficiently synthesized by atom-transfer radical addition between (R)-carvone and tetra-chloro-methane. In the mol-ecule, both chiral centres are of the absolute configuration R. The cyclo-hex-2-enone ring has an envelope conformation with the chiral C atom displaced by 0.633 (2) Šfrom the mean plane through the other five C atoms [maximum deviation = 0.036 (2) Å]. In the crystal, mol-ecules are linked via C-H⋯O inter-actions, leading to the formation of helical chains propagating along [100].

Ni(0)-CMC-Na - nickel colloids in sodium carboxymethyl-cellulose: catalytic evaluation in hydrogenation reactions.

A recyclable catalyst, Ni(0)-CMC-Na, composed of nickel colloids dispersed in a water soluble bioorganic polymer, sodium carboxymethylcellulose (CMC-Na), was synthesized by a simple procedure from readily available reagents. The catalyst thus obtained is stable and highly active in alkene hydrogenations.

2-(Naphthalen-1-yl-amino)-cyclo-hexa-nol.

The title compound, C(16)H(19)NO, was synthesized under solvent-free conditions by reaction of 7-oxa-bicyclo-[4.1.0]heptane and naphthalen-1-amine in the presence of Ca(CF(3)COO)(2) as catalyst. The cyclo-hexane ring adopts a chair conformation. In the crystal, mol-ecules are linked by inter-molecular N-H⋯O hydrogen bonds and C-H⋯π inter-actions into chains parallel to the c axis.

(5R)-5-[(1R)-2,2-Dichloro-1-methyl-cyclo-prop-yl]-2-methyl-cyclo-hex-2-en-1-one.

The title compound, C(11)H(14)Cl(2)O, was synthesized by the reaction of a dichloro-methane solution of (R)-carvone and potassium tert-butano-late in the presence of a catalytic amount of benzyl-triethyl-ammonium chloride in chloro-form. The cyclo-hexene ring adopts a half-boat conformation. The cyclo-propyl ring is unsymmetrical, the shortest C-C bond being distal to the alkyl-substituted C atom. The crystal packing is stabilized only by van der Waals inter-actions.

(S)-4-(2-Chloro-propan-2-yl)-1-(2,2,2-trichloro-eth-yl)cyclo-hexene.

The title compound, C(11)H(16)Cl(4), was synthesized by the reaction of (1S)-ß-pinene with triethyl-amine in the presence of ZnCl(2). The cyclo-hexene ring assumes a half-boat conformation. The crystal packing is governed only by van der Waals inter-actions. The structure, which has been refined in P2(1), presents a striking P2(1)/m pseudosymmetry.

rac-Ethyl (2Z)-3-{2-[(Z)-4-eth-oxy-4-oxobut-2-en-2-yl-amino]-cyclo-hexyl-amino}-but-2-enoate.

The asymmetric unit of the title compound, C(18)H(30)N(2)O(4), contains two independent mol-ecules. In each mol-ecule, the cyclo-hexane ring adopts a chair conformation with equatorial orientation of the substituents, and the conformation is stabilized by two intra-molecular N-H⋯O hydrogen bonds, forming rings of S(6) graph-set motif. One eth-oxy group and one ethyl group are disordered over two sets of sites with refined occupancy ratios of 0.704 (2):0.296 (2) and 0.505 (3):0.495 (3), respectively. In the crystal, a weak inter-molecular C-H⋯O hydrogen inter-action is observed, involving the O atom of the major component of the disordered eth-oxy group.

[(1R,4S)-(+)-3-Benzoyl-1,7,7-trimethyl-bicyclo-[2.2.1]heptan-2-olato-κO,O](η-norbornadiene)rhodium(I).

In the title complex mol-ecule, [Rh(C(17)H(19)O(2))(C(7)H(8))], the rhodium(I) metal centre is coordinated by the O atoms of a benzoyl-camphorate anion and the C=C bonds of the norbornadiene mol-ecule into a slightly distorted square-planar coordination geometry. The six-membered chelate ring is essentially planar (r.m.s. deviation = 0.0378 Å) and forms a dihedral angle of 31.67 (11)° with the phenyl ring.

(1S,2R,4S)-1-[(Benzyl-amino)-meth-yl]-4-(prop-1-en-2-yl)cyclo-hexane-1,2-diol.

The title compound, C(17)H(25)NO(2), was synthesized by epoxidation of the double bond of (S)-perillyl alcohol [(S)-4-isopropenyl-1-cyclo-hexenyl-methanol], followed by the oxirane ring-opening by benzyl-amine using [Ca(CF(3)CO(2))(2)] as catalyst under solvent-free condition at 313 K. The mol-ecular conformation is stabilized by an intra-molecular O-H⋯N hydrogen bond. In the crystal, mol-ecules are linked by inter-molecular N-H⋯O hydrogen bonds, forming chains parallel to the a axis, which are further connected by O-H⋯O hydrogen bonds into sheets parallel to (010). The absolute configuration of the mol-ecule is known from the synthetic procedure.

4-Chloro-N-methyl-2-(1,2,3,4-tetra-hydro-isoquinolin-1-yl)aniline.

The racemic title compound, C(16)H(17)ClN(2), shows a tetra-hydro-isoquinoline skeleton with a 4-chloro-N-methyl-aniline group linked to the C atom at position 1. The dihedral angle between the benzene rings is 85.82 (4)°. An intra-molecular N-H⋯N hydrogen bond occurs. In the crystal, mol-ecules are linked through inter-molecular C-H⋯π inter-actions.

[(1R)-3-Benzoyl-1,7,7-trimethyl-bicyclo-[2.2.1]heptan-2-onato-κO,O']chlorido(η-p-cymene)ruthenium(II).

The asymmetric unit of the title compound, [RuCl(C(10)H(14))(C(17)H(19)O(2))], contains two diastereomers. In both, the Ru(II) ion has a tetra-hedral coordination, formed by two O atoms of the camphor-derived ligand and the p-cymene and Cl ligands. In the crystal structure, weak inter-molecular C-H⋯Cl inter-actions link the mol-ecules into columns propagated along [010].

Tip-induced oxidation of silicene nano-ribbons.

We report on the oxidation of self-assembled silicene nanoribbons grown on the Ag (110) surface using scanning tunneling microscopy and high-resolution photoemission spectroscopy. The results show that silicene nanoribbons present a strong resistance towards oxidation using molecular oxygen. This can be overcome by increasing the electric field in the STM tunnel junction above a threshold of +2.6 V to induce oxygen dissociation and reaction. The higher reactivity of the silicene nanoribbons towards atomic oxygen is observed as expected. The HR-PES confirm these observations: even at high exposures of molecular oxygen, the Si 2p core-level peaks corresponding to pristine silicene remain dominant, reflecting a very low reactivity to molecular oxygen. Complete oxidation is obtained following exposure to high doses of atomic oxygen; the Si 2p core level peak corresponding to pristine silicene disappears.

Efficient production of few-layer black phosphorus by liquid-phase exfoliation.

Phosphorene is a new two-dimensional material that has recently attracted much attention owing to its fascinating electrical, optical, thermal and chemical properties. Here, we report on high-quality exfoliation of black phosphorus nanosheets, with controllable size produced in large quantities by liquid-phase exfoliation using N-methyl-2-pyrrolidone (NMP) as a solvent under ambient conditions. The as-synthesized few layers show a great potential for solar energy conversion based on the optical results shown in this work.

Silicon sheets by redox assisted chemical exfoliation.

In this paper, we report the direct chemical synthesis of silicon sheets in gram-scale quantities by chemical exfoliation of pre-processed calcium disilicide (CaSi2). We have used a combination of x-ray photoelectron spectroscopy, transmission electron microscopy and energy-dispersive x-ray spectroscopy to characterize the obtained silicon sheets. We found that the clean and crystalline silicon sheets show a two-dimensional hexagonal graphitic structure.