Benzoyl Valine Quasiracemates: Pairing CF3 Quasienantiomers with H to t-Butyl.

Understanding the interplay of structural features responsible for molecular assembly is essential for molecular crystal engineering. When assembling molecules with encoded motifs, first choice supramolecular strategies almost always include robust directional nonbonded contacts. Quasiracemic materials, considered near racemates since cocrystallization occurs with chemically unique components, lack a molecular framework or functional group restrictions, highlighting the importance of molecular shape to molecular assembly. Recently, our group reported quasiracemates derived from benzoyl leucine/phenylalanine derivatives with two points of chemical difference. In this study, we modified the chemical framework with valine and increased the scope of the work by imposing a larger variance in the side chain substituents. Pairing a CF3 component with quasienantiomers that differ iteratively from hydrogen to t-butyl offers an important view into the supramolecular landscape of these materials. Single-crystal X-ray crystallography and lattice energy assessments, coupled with conformational and crystal structure similarity searches, show an elevated degree of isomorphism for many of the targeted 17 racemates and quasiracemates. These benzoyl amino acid molecular architectures create extended hydrogen-bond patterns in the crystal that provide enhanced opportunities to study the shape space and molecular recognition profiles for a diverse family of quasienantiomeric components.

Synthesis, Structure and Anticancer Activity of a Dinuclear Organoplatinum(IV) Complex Stabilized by Adenine.

The dinuclear organoplatinum(IV) compound {Pt(CH3)3}2(µ-I)2(µ-adenine) (abbreviated Pt2ad), obtained by treating cubic [Pt(CH3)3(µ3-I)]4 with two equivalents of adenine, was isolated and structurally characterized by single crystal X-ray diffraction. The National Cancer Institute Developmental Therapeutics Program's in vitro sulforhodamine B assays showed Pt2ad to be particularly cytotoxic against central nervous system cancer cell line SF-539, and human renal carcinoma cell line RXF-393. Furthermore, Pt2ad displayed some degree of cytotoxicity against non-small cell lung cancer (NCI-H522), colon cancer (HCC-2998, HCT-116, HT29, and SW-620), melanoma (LOX-IMVI, MALME-3M, M14, MDA-MB-435, SK-MEL-28, and UACC-62), ovarian cancer (OVCAR-5), renal carcinoma (A498), breast cancer (BT-549 and MDA-MB-468), and triple-negative breast cancer (MDA-MB-231).

Dual space divergence in small molecule quasiracemates: benzoyl leucine and phenylalanine assemblies.

Quasiracemic materials constructed with two points of structural difference were used to understand the role molecular shape plays in molecular assembly. Hot stage, crystallographic and occupied cavity space assessments provide insight into how imposed CH3/Cl and H/CF3 structural variations placed on benzoyl leucine and phenylalanine scaffolds result in a remarkably high occurrence of cocrystal formation.

Crystal structure and Hirshfeld surface analysis of tri-aza-triborinotris[1,3,2]benzodi-aza-borole acetone disolvate.

The title compound, alternatively known as benzodi-aza-borole trimer, C18H15B3N6·2C3H6O, at 100 K crystallizes in the triclinic system, space group P . The structure displays N-H⋯O hydrogen bonding connecting the main mol-ecule with the crystallization solvent. Disorder of the main mol-ecule is observed with occupancy factors refined to 0.8922 (14):0.1078 (14). The packing of the crystal shows a parallel-displaced atom-centered orientation with 3.30 (2) Šbetween the planes of the rings. In the solid state, the title compound is linked with weak C-H⋯π inter-actions, which is supported by Hirshfeld surface analysis.

Neutrophil-Mediated Delivery of Nanocrystal Drugs via Photoinduced Inflammation Enhances Cancer Therapy.

The efficient delivery of anticancer agents into tumor microenvironments is critical for the success of cancer therapies, but it is a prerequisite that drug carriers should overcome tumor vasculature and possess high drug contents. Here, we found that photoinduced inflammation response caused the migration of neutrophils into tumor microenvironments and neutrophils transported neutrophil-targeted nanoparticles (NPs) across the tumor blood barrier. The results showed that tumor delivery efficiencies of NPs were 5% ID/g, and they were independent of particle sizes (30-200 nm) and their doses (108-1011 NPs). To efficiently deliver anticancer agents into tumors via neutrophils, we fabricated carrier-free paclitaxel nanocrystals (PTX NC). The results showed that neutrophil uptake of PTX NC did not impair neutrophil tumor infiltration, and the sustainable release of PTX from PTX NC in tumors was regulated by paclitaxel protein complexes, thus improving the mouse survival in two preclinical models. Our studies demonstrate that delivery of nanocrystal drugs via neutrophils is a promising method to effectively treat a wide range of cancers, and we have also identified a mechanism of drug release from neutrophils in tumors.

Synthesis and Determination of Anticancer Activity of Dicobalt Hexacarbonyl 2'-Deoxy-5-alkynylfuropyrimidines.

Dicobalt hexacarbonyl 5-alkynyl furopyrimidine nucleoside analogs, with 4-methylphenyl (p-tolyl) and 4-pentylphenyl substituents attached at the C-6 base position, designed in the form of ribose acetyl esters, were synthesized (42-96%). Attached at the C-5 position were propargyl alcohol, its methyl ether and acetate derivatives, butynol, and the 4-methylphenyl- (p-tolyl) and 4-pentylphenyl-substituted alkynyl groups, which were coordinated to a dicobalt hexacarbonyl unit. The structure of 5-(3-acetoxyprop-1-yn-1-yl)-6-p-tolyl-2'-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-one was determined by X-ray crystallography. Density functional theory calculations performed on the corresponding derivative yielded geometric parameters for the dicobalt hexacarbonyl adduct of this ligand. The cytotoxic activity of each of dicobalt modified nucleosides on cancer cells of different phenotypes was determined in vitro. The investigated compounds showed antiproliferative effects with median inhibitory concentration (IC50) values in the ranges of 14-90 and 9-50 µM for HeLa and K562 cells, respectively. The formation of reactive oxygen species in the presence of modified nucleosides was determined in K562 cells. The results indicate that the mechanism of action for the studied compounds may be related to the induction of oxidative stress.

Crystal structures, Hirshfeld analysis, and energy framework analysis of two differently 3'-substituted 4-methylchalcones: 3'-(N=CHC6H4-p-CH3)-4-methylchalcone and 3'-(NHCOCH3)-4-methylchalcone.

Two crystal structures of chalcones, or 1,3-diarylprop-2-en-1-ones, are presented; both contain a p-methyl substitution on the 3-Ring, but differ with respect to the m-substitution on the 1-Ring. Their systematic names are (2E)-3-(4-methylphenyl)-1-(3-{[(4-methylphenyl)methylidene]amino}phenyl)prop-2-en-1-one (C24H21NO) and N-{3-[(2E)-3-(4-methylphenyl)prop-2-enoyl]phenyl}acetamide (C18H17NO2), which are abbreviated as 3'-(N=CHC6H4-p-CH3)-4-methylchalcone and 3'-(NHCOCH3)-4-methylchalcone, respectively. Both chalcones represent the first reported acetamide-substituted and imino-substituted chalcone crystal structures, adding to the robust library of chalcone structures within the Cambridge Structural Database. The crystal structure of 3'-(N=CHC6H4-p-CH3)-4-methylchalcone exhibits close contacts between the enone O atom and the substituent arene ring, in addition to C...C interactions between the substituent arene rings. The structure of 3'-(NHCOCH3)-4-methylchalcone exhibits a unique interaction between the enone O atom and the 1-Ring substituent, contributing to its antiparallel crystal packing. In addition, both structures exhibit π-stacking, which occurs between the 1-Ring and R-Ring for 3'-(N=CHC6H4-p-CH3)-4-methylchalcone, and between the 1-Ring and 3-Ring for 3'-(NHCOCH3)-4-methylchalcone.

Anticancer Activity of Nonpolar Pt(CH3)2I2{bipy} is Found to be Superior among Four Similar Organoplatinum(IV) Complexes.

The anticancer properties of well-defined molecules serve to bolster the field of metals in medicine. Such compounds, particularly those of platinum and their closely related structural analogs, continue to be potentially highly interesting to researchers and clinicians alike. The four octahedral organoplatinum(IV) compounds [Pt(CH3)2X2{bipy-R 2 }] (X = Br, I; bipy-R 2 = 2,2'-bipyridine, 2,2'-bipyridine-4,4'-dicarboxylic acid) have been isolated and structurally characterized by single-crystal X-ray diffraction. Nuclear magnetic resonance and infrared spectroscopic data are also tabulated as useful reference values. The anticancer potential of each compound was assessed via in vitro MTT assays, using human breast cancer cells (cell line ZR-75-1). EC50 values were determined as 11.5 µM for Pt(CH3)2Br2{bipy}; 3020 µM, for Pt(CH3)2Br2{bipy-(CO 2 H) 2 }; 6.1 µM, for Pt(CH3)2I2{bipy}; and 86.0 µM, for Pt(CH3)2I2{bipy-(CO 2 H) 2 }; for comparison, the EC50 value for cisplatin against the ZR-75-1 cells was 16.4 µM. The most cytotoxic of the four compounds Pt(CH3)2I2{bipy} undergoes reaction with glutathione in a THF/water mixture at 68°C very slowly.

Synthesis, crystal structure and Hirshfeld analysis of triphenylphosphine-(4-bromophenyl)borane.

The title compound, alternatively called (4-bromophenyl)dihydrido(triphenylphosphanyl)boron, C24H21BBrP, crystallizes in the space group P-1 with one symmetry-independent molecule in the asymmetric unit. The B and P atoms both adopt the expected tetrahedral geometry. A possible intramolecular B-Hδ-...δ+H-C dihydrogen bond exists between an arene group on phosphorus and the borane center. In the solid state, the title molecule is connected to its neighbors by intermolecular C-H...π interactions, with the arene rings on the P atom acting as hydrogen-bond donors and the arene ring of the borane acting as the acceptor. Hirshfeld analysis supports the existence of these interactions, as well as weak Br...Br interactions between neighboring molecules.

Recent Advances in the Synthesis of Isoquinoline-Fused Benzimidazoles.

This review includes recent developments in the synthesis of benzo[4,5]imidazo[2,1-a]isoquinolines with particular attention given to categorizing protocols based on the structural features of the ring architecture and crystallographically characterized reaction products.

Asymmetric Synthesis of Bicyclic Pyrazolidinones through Alkaloid-Catalyzed [3+2]-Cycloadditions of Ketenes and Azomethine Imines.

A versatile asymmetric synthesis of bicyclic pyrazolidinones through alkaloid-catalyzed formal [3+2]- and [3+2+2]-cycloadditions of ketenes with azomethine imines is described. The methodology was found to be tolerant of ketene and a variety of monosubstituted ketenes (R=alkyl, OAc). The products were formed in good to excellent yields (71-99 % for 24 examples, 39 examples in all), with good to excellent diastereoselectivity in many cases (dr 3 : 1 to 27 : 1 for 22 examples), and with excellent enantioselectivity for most examples (≥93 % ee for 34 products). In the case of most disubstituted ketenes, the reaction proceeded through a [3+2+2]-cycloaddition to form structurally interesting bicyclic pyrazolo-oxadiazepinediones with moderate diastereoselectivity (dr up to 3.7 : 1) and as racemic mixtures (3 examples). The method represents the first unambiguous example of an enantioselective reaction between ketenes and a 1,3-dipole.

Extension of furopyrimidine nucleosides with 5-alkynyl substituent: Synthesis, high fluorescence, and antiviral effect in the absence of free ribose hydroxyl groups.

A novel methodology to access alkynyl nucleoside analogues is elaborated. Highly fluorescent 5-alkynylfuropyrimidines were synthesized (97-46%) and their antiviral properties investigated in vitro. Regiochemistry of the functionalization was achieved with the aid of 5-endo-dig electrophilic halocyclization of acetyl 5-p-tolyl- or 5-p-pentylphenyl-2'-deoxyuridine. Structure of one of the resulting nucleosides, 6-p-tolyl-5-iodo-2'-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-one, was confirmed by X-ray crystallography, and its conformation was compared to related nucleosides. Diverse alkynyl substituents were introduced at the heterobicyclic base C-5 position via Sonogashira coupling of 5-iodo-2'-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-ones. The resulting compounds had fluorescence emissions of 452-481 nm. High quantum yields of 0.53-0.60 were observed for 9-ethynyl-9-fluorenol and propargyl alcohol/methyl ether-modified furopyrimidines. These modified nucleosides, designed in the form of ribose acetyl esters, are potential tools for fluorescent tagging, studying nucleoside metabolism, 2'-deoxyribonucleoside kinase activity, and antiviral activity. Antiviral assays against a broad spectrum of DNA and RNA viruses showed that in human embryonic lung (HEL) cell cultures some of the compounds posess antiviral activity (EC50 1.3-13.2 µM) against varicella-zoster virus (VZV). The alkynyl furopyrimidine with two p-pentylphenyl substituents emerged as the best compound with reasonable and selective anti-VZV activity, confirming p-pentylphenyl potency as a pharmacophore.

Crystal structure and Hirshfeld analysis of 3'-bromo-4-methyl-chalcone and 3'-cyano-4-methyl-chalcone.

Two crystal structures of chalcones, or 1,3-di-aryl-prop-2-en-1-ones, are presented; both contain a methyl substitution on the 3-Ring, but differ on the 1-Ring, bromo versus cyano. The compounds are 3'-bromo-4-methyl-chalcone [systematic name: 1-(2-bromo-phen-yl)-3-(4-methyl-phen-yl)prop-2-en-1-one], C16H13BrO, and 3'-cyano-4-methyl-chalcone {systematic name: 2-[3-(4-methyl-phen-yl)prop-2-eno-yl]benzo-nitrile}, C17H13NO. Both chalcones meaningfully add to the large dataset of chalcone structures. The crystal structure of 3'-cyano-4-methyl-chalcone exhibits close contacts with the cyano nitro-gen that do not appear in previously reported disubstituted cyano-chalcones, namely inter-actions between the cyano nitro-gen atom and a ring hydrogen atom as well as a methyl hydrogen atom. The structure of 3'-bromo-4-methyl-chalcone exhibits a type I halogen bond, similar to that found in a previously reported structure for 4-bromo-3'-methyl-chalcone.

P-stereocontrolled synthesis of oligo(nucleoside N3'→O5' phosphoramidothioate)s - opportunities and limitations.

3'-N-(2-Thio-1,3,2-oxathiaphospholane) derivatives of 5'-O-DMT-3'-amino-2',3'-dideoxy-ribonucleosides (NOTP-N), that bear a 4,4-unsubstituted, 4,4-dimethyl, or 4,4-pentamethylene substituted oxathiaphospholane ring, were synthesized. Within these three series, NOTP-N differed by canonical nucleobases (i.e., AdeBz, CytBz, GuaiBu, or Thy). The monomers were chromatographically separated into P-diastereomers, which were further used to prepare NNPSN' dinucleotides (3), as well as short P-stereodefined oligo(deoxyribonucleoside N3'→O5' phosphoramidothioate)s (NPS-) and chimeric NPS/PO- and NPS/PS-oligomers. The condensation reaction for NOTP-N monomers was found to be 5-6 times slower than the analogous OTP derivatives. When the 5'-end nucleoside of a growing oligomer adopts a C3'-endo conformation, a conformational 'clash' with the incoming NOTP-N monomer takes place, which is a main factor decreasing the repetitive yield of chain elongation. Although both isomers of NNPSN' were digested by the HINT1 phosphoramidase enzyme, the isomers hydrolyzed at a faster rate were tentatively assigned the R P absolute configuration. This assignment is supported by X-ray analysis of the protected dinucleotide DMTdGiBu NPSMeTOAc, which is P-stereoequivalent to the hydrolyzed faster P-diastereomer of dGNPST.

Benzobis(imidazolium) salts as templates for the self-assembly of starburst [24]pseudorotaxanes and their corresponding carbene-based classic [22]pseudorotaxanes.

Benzobis(imidazolium) salts ([BBI-H2-R4]2+, R = alkyl, aryl) interact with crown ethers through a combination of hydrogen bonds, ion-dipole, and π-π stacking interactions to form starburst [24]pseudo-rotaxanes. This new recognition motif allows the extension of four side-arms directly from the cavity of the crown ether, thus positioning the wheel component in a straddled orientation onto the axle, while their carbene-based derivatives show the classical shape of regular [22]pseudorotaxanes.

Multiple coordination modes of a new ditopic bis(pyrazolyl)methane-based ligand.

A new ditopic ligand, N-(2,2-bis(pyrazolyl)ethyl)-2,2-bis(pyrazolyl)acetamide ((pz)2CH-C(O)-NH-CH2-CH(pz)2, L4Pz, pz = pyrazolyl ring), comprising two bis(pyrazolyl)methane donor groups linked via an amide bridge, has been prepared from the reaction of HOOCCH(pz)2 and H2NCH2CH(pz)2. The ligand coordinates to various metallic salts (i.e. AgO3SCF3, PdCl2, Re(CO)5Br, and Fe(BF4)2), in either a κ2-µ-κ2 or a κ3-µ-κ2 fashion, depending on the coordination preferences of the metallic center. These compounds were characterized by NMR, UV-Vis and IR spectroscopy, and in solid state by single crystal X-ray diffraction. In the case of silver(i), a mono-dimensional coordination polymer was obtained, while the others were found to be discrete complexes. The synthesis and characterization of a heterobimetallic complex is also described. In solid state, all compounds are associated into supramolecular architectures via hydrogen bonding and pyrazolyl embrace interactions.

Organometallic Nucleosides: Synthesis and Biological Evaluation of Substituted Dicobalt Hexacarbonyl 2'-Deoxy-5-oxopropynyluridines.

Reactions of dicobalt octacarbonyl [Co2(CO)8] with 2'-deoxy-5-oxopropynyluridines and related compounds gave dicobalt hexacarbonyl nucleoside complexes (83-31 %). The synthetic outcomes were confirmed by X-ray structure determination of dicobalt hexacarbonyl 2'-deoxy-5-(4-hydroxybut-1-yn-1-yl)uridine, which exhibits intermolecular hydrogen bonding between a modified base and ribose. The electronic structure of this compound was characterized by the DFT calculations. The growth inhibition of HeLa and K562 cancer cell lines by organometallic nucleosides was examined and compared to that by alkynyl nucleoside precursors. Coordination of the dicobalt carbonyl moiety to the 2'-deoxy-5-alkynyluridines led to a significant increase in the cytotoxic potency. The cobalt compounds displayed antiproliferative activities with median inhibitory values (IC50) in the range of 20 to 80 µm for the HeLa cell line and 18 to 30 µm for the K562 cell line. Coordination of an acetyl-substituted cobalt nucleoside was expanded by using the 1,1-bis(diphenylphosphino)methane (dppm) ligand, which exhibited cytotoxicity at comparable levels. The formation of reactive oxygen species in the presence of cobalt compounds was determined in K562 cells. The results indicate that the mechanism of action for most antiproliferative cobalt compounds may be related to the induction of oxidative stress.

Correction: Sisters together: co-sensitization of near-infrared emission of ytterbium(iii) by BODIPY and porphyrin dyes.

Correction for 'Sisters together: co-sensitization of near-infrared emission of ytterbium(iii) by BODIPY and porphyrin dyes' by Hongshan He et al., Chem. Commun., 2017, 53, 10120-10123.

Sisters together: co-sensitization of near-infrared emission of ytterbium(iii) by BODIPY and porphyrin dyes.

A ytterbium(iii) acetate complex with a BODIPY and a porphyrin as co-sensitizers emits strongly at 978 nm over a broader excitation window between 450-560 nm.

Multicomponent reaction through cooperative trio catalysis incorporating enamine, Brønsted acid and metal Lewis acid catalysis: a concise route to access chromans.

An atom-economical multicomponent cascade reaction of salicylaldehydes, cyclohexanones and arylamines has been developed for the synthesis of three-ring fused chromans. This reaction was achieved through cooperative enamine-metal Lewis acid assisted Brønsted acid catalysis, furnishing the products in excellent yields with good diastereoselectivity.