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.
This review includes recent developments in the synthesis of benzo4,5imidazo2,1-
isoquinolines with particular attention given to categorizing protocols based on the structural features of the ring ...architecture and crystallographically characterized reaction products.
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 CH
3
/Cl and H/CF
3
structural variations placed on benzoyl leucine and phenylalanine scaffolds result in a remarkably high occurrence of cocrystal formation.
Small molecule quasiracemates developed with two points of structural difference were prepared using benzoyl leucine and phenylalanine molecular frameworks and CH
3
/Cl or H/CF
3
pendant groups.
A new asymmetric synthesis of bicyclic pyrazolidinones through an alkaloid-catalyzed formal 3 + 2 cycloaddition of in situ generated ketenes and azomethine imines is described. The products were ...formed in good to excellent yields (52–99% for 17 examples), with good to excellent diastereoselectivity (dr 5:1 to 27:1 for 11 examples), and with excellent enantioselectivity in all cases (≥96% ee). This method represents the first unambiguous example of an enantioselective reaction between ketenes and a 1,3-dipole.
An efficient environmentally benign route for the synthesis of benzimidazo2,1- a isoquinoline has been developed by reacting 2-ethynylbenzaldehyde and related substituted alkynylbenzaldehydes with ...variously substituted ortho -phenylenediamines and aliphatic amines in ethanol. This method provides a convenient, room temperature, atom-economical, and catalyst-free access to diversely substituted isoquinoline fused benzimidazoles. Regioselectivity of the reaction, as referred to o -phenylenediamines, was confirmed by X-ray crystallography. The reaction was found to occur in three major steps (imine formations, cyclization, and aromatization) and a mechanism has been proposed.
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.
Understanding the interplay of structural features responsible for molecular assembly is essential for molecular crystal engineering. When assembling molecules with encoded motifs,
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 CF
component with quasienantiomers that differ iteratively from hydrogen to
-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.
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.
The catalytic asymmetric synthesis of bicyclic pyrazolidinones through alkaloid‐catalyzed formal 3+2‐ and 3+2+2‐cycloadditions of in situ‐generated and pre‐generated ketenes with azomethine imines is described. The method provides good to excellent yields (71–99 % for 24 examples, 39 examples in all), good to excellent diastereoselectivity (dr 3 : 1 to 27 : 1) and excellent enantioselectivity for most examples (≥93 % ee for 34 products).
New additions to quasiracemic materials have been developed by cocrystallizing a ternary component - hydrogen oxalate - with pairs of amino acid quasienantiomers where at least one of the side-chain ...R groups contains a sulfur atom. Of the eight quasiracemates investigated, six exhibit crystal packing that drastically deviates from the expected centrosymmetric alignment present in the racemic counterparts and the extant database of quasiracemic materials. These structures were quantitatively assessed for conformational similarity (CCDC-Mercury structure overlay) and the degree of inversion symmetry (Avnir's Continuous Symmetry Measures) for each quasienantiomeric pair. Despite the variance in quasienantiomeric components, these structures exhibit a high degree of isostructurality where the principal components assemble by a complex blend of common N
+
-H O and O-H O
−
interactions. These charge-assisted hydrogen-bonded networks form thermodynamically favored crystal packing that promotes cocrystallization of a structurally diverse set of quasienantiomeric components.
A new family of quasiracemic materials constructed from sulfur-containing amino acid hydrogen oxalates form supramolecular assemblies that divert significantly from near centrosymmetric alignment.
reaction: see text 5-Endo-dig electrophilic cyclization of 1,4-diaryl but-3-yn-1-ones with N-bromosuccinimide or N-iodosuccinimide/acetone and iodine monochloride/CH(2)Cl(2), at room temperature, in ...the absence of base, provides 3-halo-2,5-diarylfurans with excellent regiocontrol and high yields (81-94%).
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