Bromhexine and its fumarate salt: Crystal structures, Hirshfeld surfaces and dissolution study.

Bromhexine is an expectorant drug repurposing as a TMPRSS2 inhibitor, which has also been proposed for potential treatment in COVID-19 infection. Multicomponent crystal strategy has been applied in bromhexine to improve its poor solubility, which limits its bioavailability and efficacy. A new bromhexine crystal and its fumarate salt crystal have been successfully obtained by slow evaporation technique. Both compounds have been characterized by X-ray single-crystal diffraction, TGA and FT-IR spectroscopy. Hirshfeld surface analysis has been carried out to further quantify the patterns of intermolecular interactions. Compared with bromhexine, the multicomponent crystal with pharmaceutically acceptable conformer of fumaric acid shows improved thermal stability and solubility in water.

Unraveling the Mechanisms of the Excited-State Intermolecular Proton Transfer (ESPT) for a D-π-A Molecular Architecture.

Precise revealing the mechanisms of excited-state intermolecular proton transfer (ESPT) and the corresponding geometrical relaxation upon photoexcitation and photoionization remains a formidable challenge. In this work, the compound (E)-4-(((4H-1,2,4-triazol-4-yl)imino)methyl)-2,6-dimethoxyphenol (TIMDP) adopting a D-π-A molecular architecture featuring a significant intramolecular charge transfer (ICT) effect has been designed. With the presence of perchloric acid (35 %), TIMDP can be dissolved through the formation of a HClO4 -H2 O-OH(TIMDP)-N(TIMDP) hydrogen-bonding bridge. At the ground state, the ICT effect is dominant, giving birth to crystals of TIMDP. Upon external stimuli (e.g., UV light irradiation, electro field), the excited state is achieved, which weakens the ICT effect, and significantly promotes the ESPT effect along the hydrogen-bonding bridge, resulting in crystals of [HTIMDP]+ ⋅[H2 O]⋅[ClO4 ]- . As a consequence, the mechanisms of the ESPT can be investigated, which distorted the D-π-A molecular architecture, tuned the emission color with the largest Stokes shift of 242 nm, and finally, high photoluminescence quantum yields (12 %) and long fluorescence lifetimes (8.6 µs) have achieved. These results not only provide new insight into ESPT mechanisms, but also open a new avenue for the design of efficient ESPT emitters.

Porous High-Valence Metal-Organic Framework Featuring Open Coordination Sites for Effective Water Adsorption.

The design and preparation of a porous high-valence metal-organic framework (MOF) featuring open coordination sites are of utmost importance for the development of adsorbent materials. Here in this work, the three-dimensional (3D) high-valence MOF [Er(dcbp)3/2(DMF)(H2O)2]·2H2O (HV-MOF-1; H2dcbp = 4,4'-dicarboxy-2,2'-bipyridine, DMF = N,N-dimethylformamide), which possesses permanent porosity and two open coordination sites, has been prepared and characterized. In the 3D framework, the dcbp molecules display two different bridging styles, resulting in ordered diamondlike pores with bared carboxyl oxygen and pyridine nitrogen atoms on dcbp exposed directly to the pores, generating hydrophilic characteristics and high water affinity. In addition, the open coordination sites act as arms to fix the adsorbed water molecules, providing high water adsorption capacity (5.95 mmol g-1) and selectivity. More importantly, the activated HV-MOF-1 species shows an energy-saving step for recycling (operation under 120 °C), demonstrating promise as a candidate for an adsorbent material with considerable water adsorption-desorption cycles.

Ambient-Temperature Spin-State Switching Achieved by Protonation of the Amino Group in [Fe(H2Bpz2)2(bipy-NH2)].

Magnetism of a complex [Fe(H2Bpz2)2(bipy-NH2)] (H2Bpz2 = dihydrobis(1-pyrazolyl)borate, bipy-NH2 = 4,4'-diamino-2,2'-bipyridine) has been altered from paramagnetic to spin-crossover (SCO) behavior, through protonation of one amino group of bipy-NH2 with CF3SO3H. Complete SCO transition, both in solid state and in solution, occurs at ambient temperature.

[Advances in the study of site-specific antibody-drug conjugates].

Antibody drug conjugates (ADCs) are an emerging class of targeted therapeutics with the potential to improve therapeutic index over the traditional chemotherapy. However, it is difficult to control the site and stoichiometry of conjugation in mAb, typically resulting in heterogeneous mixtures of ADCs that are difficult to optimize. New methods for site-specific drug attachment allow development of more homogeneous conjugates and control of the site of drug attachment. In this article, the new literature on development of ADCs and site-specific ADCs is reviewed. In addition, we summarized the various strategies in production of site-specific ADCs.

Build 3D Nanoparticles by Using Ultrathin 2D MOF Nanosheets for NIR Light-Triggered Molecular Switching.

The coordination interactions between transition-metal ions (Cu2+, Ag+) and sulfur atoms on ultrathin two-dimensional (2D) nanosheets of spin-crossover (SCO) metal-organic frameworks {[Fe(1,3-bpp)2(NCS)2]2}n (1,3-bpp = 1,3-di(4-pyridyl)propane), which constructed the ultrathin 2D nanosheets into three-dimensional (3D) nanoparticles, have made a profound effect on the SCO performance. Compared with 2D nanosheets, both the intraligand π-π* transition band and the metal-to-ligand charge transition band from the d(Fe) + π(NCS) to π*(1,3-bpp), for the 3D nanoparticles, have shown dramatic blue-shifts; meanwhile, the d-d transition band for the high-spin (HS) state Fe(II) ions has been generated, suggesting significantly the influence of 3D assemble-caused dimensional changes on the solid-state SCO performance of ultrathin 2D nanosheets. More importantly, by loading on the ytterbium ion (Yb3+)-sensitized hexagonal phase upconverting nanoparticles in the aqueous colloidal suspension, the near infrared (NIR) light (980 nm) triggered HS (high spin) to LS (low spin) state transitions have been observed, demonstrating the achievement of challenging target of NIR light-triggered molecular conversion under environment conditions.

Antibody-drug conjugates as targeted cancer therapeutics.

Traditional chemotherapy has become one of the essential treatments of cancer. However, cytotoxic agents are not tumor specific, which would cause serious side effects. Antibody-drug conjugates (ADCs), also called immunoconjugates, belong to the "targeted chemotherapeutics" category of anti-cancer drugs. ADCs are composed of three components including the cytotoxic drug, the monoclonal antibody, and the linker connecting the drug to the antibody. With the special-binding between antibody and antigen expressed on the surface of targeted cancer cells, ADCs provide a method to achieve excellent localization of the drug at the desired site in the body. The internalization and formation of ADCs are crucial in designing and applying an antibody conjugate to a particular disease model. In this review, we summarize three distinct internalization routes of ADCs and analysis the structure of ADCs. We also discuss in detail the categories and interaction of every component, as well as their influence to targeting property, liability and activity.

Bis{2-meth-oxy-6-[(3-pyrid-yl)methyl-imino-meth-yl]phenolato}copper(II).

In the mononuclear title complex, [Cu(C(14)H(13)N(2)O(2))(2)], the Cu(II) atom lies on an inversion centre and adopts a square-planar coordination geometry. The dihedral angle formed by the pyridine and benzene rings is 74.61 (5)°. Intra-molecular C-H⋯O hydrogen bonds are present. The crystal structure is stabilized by weak aromatic π-π stacking inter-actions involving neighbouring pyridine rings [centroid-centroid distance = 3.853 (2) Å].

Bis{µ-2-[1-(2-Pyridylmethyl-imino)eth-yl]phenolato}bis-[azido-copper(II)].

The title compound, [Cu(2)(C(14)H(13)N(2)O)(2)(N(3))(2)], was synthesized by the reaction of Cu(NO(3))(2)·3H(2)O with the Schiff base 2-[1-(2-pyridylmethyl-imino)eth-yl]phenol (HL) in methanol-water solution, adding NaN(3) as the bridging ligand. The asymmetric unit contains one half-mol-ecule, the other half being generated by the inversion center. Each Cu(II) atom shows a slightly distorted trigonal-pyramidal geometry formed by two N atoms and one O atom from one Schiff base ligand, by another O atom of a second Schiff base ligand and by an azide N atom. The crystal structure is stabilized by intermolecular C-H⋯N hydrogen bonds.

Di-µ-chlorido-bis-[aqua-(2,2'-bipyridine-κN,N')chloridocobalt(II)].

The title complex, [Co(2)Cl(4)(C(10)H(8)N(2))(2)(H(2)O)(2)], is composed of two Co(II) atoms, each hexa-coordinated by three Cl atoms, one 2,2'-bipyridine (bpy) ligand and one water mol-ecule in a distorted octa-hedral geometry. Neighboring Co(II) atoms are linked together by two Cl bridges, forming a dinuclear Co(II) complex with inversion symmetry. There are inter-molecular O-H⋯Cl hydrogen bonds and inter-molecular π-π stacking inter-actions between adjacent bpy ligands [centroid-centroid distance = 3.617 (2) Å] in the structure.

Aqua-(1,10-phenanthroline-κN,N')bis-(trimethyl-acetato)-κO,O';κO-cobalt(II).

In the title compound, [Co(C(5)H(9)O(2))(2)(C(12)H(8)N(2))(H(2)O)], the Co(II) atom is coordinated in a distorted octahedral environment by three carboxyl O atoms of two trimethyl-acetate ligands, one aqua O atom and two N atoms from 1,10-phen-anthroline. The crystal structure is stabilized by O-H⋯O hydrogen bonds and π-π stacking inter-actions [inter-planar distance between inter-digitating 1,10-phenanthroline ligands = 3.378 (2) Å].

Enhanced treatment effect of nanoparticles containing cisplatin and a GSH-reactive probe compound.

Cisplatin is a highly effective antitumor drug, which can kill cancer cells by crossing-linking DNA and inhibiting transcription, but this process is limited by the combination of cisplatin and many endogenous nucleophiles, such as glutathione (GSH). Thus, when cisplatin enter cells, it is potentially vulnerable to cytoplasmic inactivation by GSH. To settle this bottleneck, we designed and synthesized a probe compound (Probe 1) and fabricated pH-responsed cisplatin, Probe 1-loaded lipid-polymer hybrid NanoParticles (CPNPs) using a single-step sonication method. Probe 1 can specifically bind to GSH, thus avoiding the combination of GSH and cisplatin, and enhancing the pharmacological activity of cisplatin. In vitro studies have suggested CPNPs, compared with cisplatin, loaded lipid-polymer hybrid NanoParticles CNPs (Not contain Probe 1), could efficiently kill MCF-7 human breast cancer cells and A549 human nonsmall lung cancer cell. Hence, the CPNPs provided a new idea for treating cancer.

Ultralarge Dielectric Relaxation and Self-Recovery Triggered by Hydrogen-Bonded Polar Components.

Subtle integration of rotatable polar components into dielectric crystals can contribute significantly to adjustable switching temperatures ( Ts) and dielectric relaxation behaviors. Currently, one of the biggest challenges lies in the design of optimal polar components with moderate motion resistance in a crystalline system. In this work, we demonstrate that under refrigerator conditions, rotatable hydrogen-bonded one-dimensional (1D) cationic chains, {[C2H6N5]+} n (C2H6N5 = 3,5-diamino-1,2,4-triazolinium), and two-dimensional (2D) anionic layers, {[(H2O)2·SO4]2-} n, can be generated in an organic salt, 3 ([C2H6N5]2·[(H2O)2·SO4]). Compared with the nonhydrated precursor, 2 ([C2H7N5]·[SO4]), the rotation of these 1D and 2D ionic species triggers a reversible phase transition and dielectric switching in 3. In addition, the significantly sluggish rotation of the 1D cationic chains from parallel to unparallel stacking and the counter-clockwise rotation of the 2D anionic layers, compared with their reverse processes, induce a frequency-dependent dielectric response with a more highly adjustable heating Ts↑ than the cooling Ts↓. More importantly, 3 possesses excellent self-recovery ability attributed to the highly dynamic character of the hydrogen-bonded ionic species. The strategy here can provide a fairly good model for designing dielectric crystals with desired rotatable polar components.

Bis[µ-3-(2-hydroxy-ethyl)-2-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-olato-κN,O:O]bis[aquachloridocopper(II)].

In the dinuclear centrosymmetric copper(II) title compound, [Cu(2)(C(11)H(11)N(2)O(2))(2)Cl(2)(H(2)O)(2)], each Cu(II) ion has a slightly distorted trigonal-bipyramidal geometry and is coordinated by one N and one O atom from one 3-(2-hydroxy-ethyl)-2-methyl-4-oxopyrido[1,2-a]pyrimidin-9-olate ligand, another O atom from the second ligand, one water mol-ecule and one Cl atom. The crystal structure involves inter-molecular C-H⋯Cl, O-H⋯Cl and O-H⋯O hydrogen bonds.

Methyl 5-[N,N-bis-(methoxy-carbonyl-meth-yl)amino]-4-cyano-2-methoxy-carbonyl-3-thio-phene-ethan-o-ate.

In the title compound, C(16)H(18)N(2)O(8)S, derived from ranelic acid, there is a highly substituted thio-phene ring. The crystal structure involves inter-molecular C-H⋯O and C-H⋯S hydrogen bonds.

2,2'-[1-(2,4,6-Trichlorophenyl)-1H-1,2,4-triazole-3,5-diyl]diphenol.

The title compound, C(20)H(12)Cl(3)N(3)O(2), was synthesized by the reaction of 2-(2-hydroxy-phen-yl)benz[e][1,3]oxazin-4-one with 2,4,6-trichloro-phenyl-hydrazine in ethanol. The trichloro-phenyl ring is nearly perpendicular to the triazole plane [dihedral angle 80.56 (8)°], whereas the two hydroxy-phenyl rings are approximately coplanar with the triazole ring [dihedral angles of 2.79 (12) and 8.00 (14)°]. Intra-molecular O-H⋯N hydrogen bonding is observed between the hydroxy-phenyl and triazole rings.

catena-Poly[[silver(I)-µ-[N-(4-pyridyl-meth-yl)pyridine-4-carboxamide-κN:N']] nitrate monohydrate].

The title coordination polymer, {[Ag(C(12)H(11)N(3)O)]NO(3)·H(2)O}(n), has a polycationic chain motif in which the Ag atom is bridged by the heterocyclic ligand; the Ag atom shows linear coordination. If the two long Ag⋯O(nitrate) inter-actions [2.794 (6) and 2.867 (5) Å] are regarded as bonds, the compound adopts a three-dimensional network structure. The water mol-ecule consolidates the network structure by forming hydrogen bonds, one to the polycationic chain and one to the nitrate anion.

Decacarbonyl-1κC,2κC,3κC-µ-hydrido-1:2κH:H-(µ-quinoline-2-thiol-ato-1:2κS:S)diosmium(I)osmium(0)(3 Os-Os).

The title compound, [Os(3)(C(9)H(6)NS)H(CO)(10)], contains a nearly equilateral triangle of Os atoms. Two of the Os atoms are bridged by an S atom of the quinoline-2-thiol-ate ligand. Ten carbonyl groups complete the cluster, resulting in a distorted octa-hedral geometry for each Os atom. The hydride atom, which was located in a difference Fourier map and refined isotropically, bridges the shortest Os-Os edge.

Poly[diaqua-bis(µ-azido-κN:N)bis-(µ(3)-1-oxoisonicotinato-κO:O':O'')dicadmium(II)].

In the title compound, [Cd(2)(C(6)H(4)NO(3))(2)(N(3))(2)(H(2)O)(2)](n), one Cd(II) atom is located on an inversion center and is coordinated by four O atoms from four bridging 1-oxoisonicotinate ligands and two N atoms of two bridging azide ligands in a slightly distorted octa-hedral geometry. The other Cd(II) atom, also lying on an inversion center, is coordinated by four O atoms from two bridging 1-oxoisonicotinate ligands and two water mol-ecules and two N atoms of two bridging azide ligands in a slightly distorted octa-hedral geometry. The Cd atoms are connected via the 1-oxoisonicotinate and azide ligands into a two-dimensional coordination network. The crystal structure involves O-H⋯N and O-H⋯O hydrogen bonds.

Poly[(µ(6)-benzene-1,2,4,5-tetra-carboxyl-ato)bis-(1,10-phenanthroline-κN,N')dimanganese(II)].

The title polymeric compound, [Mn(2)(C(10)H(2)O(8))(C(12)H(8)N(2))(2)](n), was obtained by the reaction of manganese(II) chloride tetra-hydrate with benzene-1,2,4,5-tetra-carboxylic acid (H(4)bta) in aqueous solution. Each Mn(2+) ion is coordinated in a distorted octa-hedral geometry by two N atoms from one 1,10-phenanthroline ligand and four O atoms [Mn-O = 2.116 (2)-2.237 (2) Å] from three bta(4-) ligands, which also act as bridging groups between the Mn(2+) ions.