The antioxidant and physicochemical properties of microencapsulated bioactive compounds in Securigera securidaca(L.)seed extract by co-crystallization

Securigera securidaca seed is a good source of phenolic compounds with high antioxidant properties.Preservation and maintenance of natural antioxidants have always been a challenge and microencapsulation is a suitable method for this purpose.In this study,the chemical compounds of the plant seed extract were identified by GC/MS device.Bioactive compounds from the seed ethanolic extract were microencapsulated in the sucrose matrix during the co-crystallization process.The evaluations included total phenolic compounds,radical scavenging ability,production efficiency,moisture content,and flowability characteristics of the produced powders,such as compressibility index,Hausner ratio,and angle of repose.The results showed significant differences in the phenolic compounds and the radical scavenging ability between the control sample and the co-crystallized powder(P<0.05).The production efficiency and the moisture content of extract-containing co-crystallized powder were 84%and 0.14%,respectively.The particle size difference of the microencapsulated powder could significantly affect the powder flowability characteristics(P<0.05),and particles with a size of 1 mm showed better flowability behaviour.FT-IR charts for samples revealed chemical bonds specific to saccharose molecule indicating no changes in covalent bonds present in saccharose molecule structure after the process.Scanning electron microscope images showed the presence of vacant spaces and porosity in the structure of saccharose crystals formed during the process of crystallization.As a result,the co-crystallized powder obtained from the plant extract can be used as an appropriate antioxidant in the food and pharmaceutical formulations.

One-step rapid preparation of CL-20/TNT co-crystal assembly and spheroidized coating based on droplet microfluidic technology

Energetic materials pose challenges in preparation and handling due to their contradictory properties of high-energy and low-sensitivity.The emergence of co-crystal explosives is a new opportunity to change this situation.If the co-crystal explosive is coated into spherical particles with uniform particle size distribution,this contradiction can be further reduced.Therefore,binder-coated hexanitrohexaazaisowurtzitane/2,4,6-trinitrotoluene(CL-20/TNT)co-crystal microspheres were prepared by droplet microfluidic technology in this work.The coating effects of different binder formulations of nitrocellulose(NC)and NC/fluorine rubber(F2604)on the co-crystal spheres were studied.The scanning electron microscopy(SEM)results showed that the use of droplet microfluidic technology with the above binders can provide co-crystal microspheres with regular spherical morphology,uniform particle size distribution and good dispersion.X-ray diffraction(XRD),fourier-transform infrared(FT-IR),differential scanning calorimetry(DSC)and thermo-gravimetric(TG)methods were employed to compare the properties of the co-crystal microspheres,raw material and pure co-crystal.The formation of CL-20/TNT co-crystal in the microspheres was confirmed,and the co-crystal microspheres exhibited better thermal stability than the raw material and pure co-crystal.In addition,the mechanical sensitivity and combustion performance of the co-crystal microspheres were further studied.The results showed that the co-crystal microspheres were more insensitive than CL-20 and pure co-crystal,and displayed excellent self-sustained combustion performance and theoretical detonation performance.This study provides a new method for the fast,simple and one-step preparation of CL-20/TNT co-crystal microspheres,with binder coating,uniform particle size distribution,and excellent performance level.

Preparation of reduced sensitivity co-crystals of cyclic nitramines using spray flash evaporation

The present day weapon technology demands novel energetic materials that exhibit simultaneous high explosive yield and reduced sensitivity.This article demonstrates application of spray evaporation to prepare reduced sensitive co-crystals of high performance nitramine explosives like HMX and CL-20 with a relatively less insensitive explosive 1,1-diamino-2,2-dinitroethylene or FOX-7.Stronger intermolecurar hydrogen bonding in FOX-7 is responsible for limited solubility in nost of o rganic solvents.Large solubility differences of FOX-7 with HMX and CL-20 restricts ifs co-crystallization through classical methods that yields thermodynamically favorable product.Spray flash evaporation,a kinetic crystallization method,has been therefore adopted and could successfully produce CL-20/FOX-7(2:1) and HMX/FQX-7(4:1) co-crystals.The fine powdered materials obtained were characterized by SEM,powder XRD,Raman spectro scopy,DSC-TGA etc.Multipoint Raman spectra showed consistent occurrence of spectral features indicating stoichiometric co-existence of ingredients in the crystal lattices.DSC analysis showed absence of all thermally assisted solidsolid phase transformation in the co-crystals as they were observed in pristine materials.The thermal stability calculated in terms of activation barrier fordecomposition,revealed the CL-20/FOX-7 co-crystal to be interlediately stable on comparison to their constituents while,the HMX/FOX-7 co-crystal is more stable.Compared to pure HMX and CL-20,both the co-crystals have shown higher insensitivity to impact force,suggesting them to be suitable for future generation insensitive munitions.

Structure of Co-crystals Formation from Imidazolium and Aromatic Ligands

In this study, two new co-crystals based on rigid imidazolium ligand （2,2＇-（（1,1’- biphenyl）-4,4＇-diyl）bis（2H-imidazo[1,5-a]pyridine-4-ium） hexafluorophosphate （L）） and 4,4＇- bipyridine （Bpy） and benzene （Ben）, formulated as L（Bpy）0.5 （co-crystal 1） and L（Ben） （co-crystal 2）, were obtained. Crystal data for 1： Pī space group with α = 10.921（4）, b = 16.998（6）, c = 17.666（6） A, α = 95.720（7）, β = 104.272（7）, γ = 93.340（6）°, V = 3150.5（19） A^3 and Z = 2; and crystal data for 2： monoclinic C2/m space group with α = 25.90（2）, b = 9.631（9）, c = 6.371（6） A, β = 95.26（2）°, V = 1583（2） A3 and Z = 2. Co-crystal 1 was dependent on hydrogen bonds and π···π stacking, while only hydrogen bonds are present in 2. Two new co-crystals were characterized by IR, NMR spectra, thermogravimetric and ultraviolet absorption analyses.

Non-merohedrally Twinned Crystal Structure of the Co-crystal Ethyl 6-(2-5-(Ethoxycarbonyl)-pyridin-2-yl-1,2-dihydroxyethyl)pyridine-3-carb-oxylateethyl 6-(2-5-(Ethoxycarbonyl)pyridin-2-yl-2-hydroxyacetyl)pyridine-3-carboxylate(0.69/0.31)

The two component molecules of the co-crystal 0.69（C18H2ON206）.0.31（C18H18N2O6） lie on a center-of-inversion that exists midway along the ethylene chain connecting the two aromatic rings. The two molecules are superimposed. The crystal is also a non-morohedral twin with a minor 37.7（2）% component. The refinement of this twinned and disordered crystal structure is detailed. Crystal data： C18H19.38N2O6, monoclinic, P21/c, a = 17.1687（8）, b = 5.4389（2）, c = 9.3261（4） A, b = 95.270（5）° and V= 867.18（6） A3 at -173 ℃.

Theophyllineecitric acid co-crystals easily induced by DSCeFTIR microspectroscopy or different storage conditions

A simultaneous differential scanning calorimetryeFourier transform infrared(DSCeFTIR)microspectroscopy was used to quickly investigate the co-crystal formulation between anhydrous theophylline(TP)and anhydrous citric acid(CA)in a one-step procedure.The raw materials of TP andCA,aswell as the intactTPeCA co-crystal prepared by slow solvent evaporation were also respectively examined by this approach.The result indicates that the TPeCA cocrystal formulation was easily induced using this DSCeFTIR technique.The thermaldependent changes in three-dimensional FTIR spectral contour profiles were started from 165
C to induce the co-crystal formation of TPeCA,which was prior to the endothermic peak at 173
C found in the conventional DSC curve.Beyond 165
C,several new IR absorption peaks at 3515,3124,1730,1710,1677,1648,1552 and 1265 cm1 corresponding to unique IR spectral peaks of intact TPeCA co-crystal were observed.The DSCeFTIR microspectroscopic results also evidenced the dimeremonomer transition of CA,but there were no markedly changes for TP or intact TPeCA co-crystal before its fusion.This strongly implies that the DSCeFTIR technique giving spectroscopic and thermodynamic information could simultaneously induce and identify the TPeCA co-crystal formation and phase transition of samples.Different storage conditions affecting the stability of both physical mixture and ground mixture of TPeCA were also determined.The physicalmixture of TPeCA after storing at 55
C/75%RH condition for one day was fast transformed to TPeCA co-crystal,indicating that TPeCA co-crystal was easily induced under accelerated storage condition.While the co-crystal formed from TPeCA ground mixture was stable in both 25
C/75%RH and 55
C/75%RH conditions.

Synthesis,Crystal Structure and Evaluations of Its Cytotoxicity,Anti-microbial and Anti-hydroxyl Radical Activities of a New Co-crystal Compound(C6H6Cl2N2O2S)·(Phen)·H2O

Co-crystal is a very potential kind of drug solid forms, and has a far-reaching influence on designing and preparing drugs. A new 1：1：1 co-crystal compound consisting of 4-amino-3,5-dichloro-benzenesulfonamide, 1,10-phenanthroline and water was synthesized, and its crystal structure was characterized by X-ray diffraction method. The compositions of the co-crystal are self-assembled into a three-dimensional network structure via intermolecular interactions including hydrogen bonds, π-π stacking, Cl？？？Cl interactions and van der Waals＇ forces. According to the evaluations of cytotoxicity assays, anti-microbial and anti-hydroxyl radicals, this co-crystal is a potential drug.

Synthesis, Structure and Geometrical Calculation of a Novel Co-crystal of {[4-Bromo-2-(benzimidazol-2-yl)phenolato][2-(1-butylbenzimidazol-2-yl)phenolato]zinc(Ⅱ)] and Bis[μ-2-(1-butylbenzimidazol-2-yl)phenolato]-1κN^3:2κO;1κO:2κN^3-bis{[2-(1-butylbe

The title compound has been synthesized and characterized crystallographicaUy. It is a co-crystal consisting of two different neutral zinc（H） complexes with Hbpbm （Hbpbm = 4- bromo-2-（benzimidazol-2-yl）phenol） and Hnpbm （Hnpbm = 2-（1-butylbenzimidazol-2-yl）phenol）. One is a monomeric mixed-ligand complex of [Zn（bpbm）（npbm）] 1 and the other a dimer of [Zn2（npbm）4] 2 with their ratio of 2：1. Thus the overall formula for the title compound is 21.2. Adjacent 1 and 2 are connected to each other by intermolecular hydrogen bonding interactions in the lattice. The crystal data： monoclinic, space group P21/c, a = 15.0141（12）, b = 20.9941（17）, c = 18.4686（15） A, β = 97.445（2）°, V = 5772.4（8） A^3, Mr= 2429.68, Z = 2, Dc = 1.398 g/cm^3,μ = 1.579 -1 mm , F（000） = 2504, R = 0.0637 and wR = 0.1771 for 6464 observed reflections （I 〉 2σ（I））. The geometrical structure for 1 has also been theoretically optimized and compared with the experimental one.

One-dimensional molecular co-crystal alloys capable of full-color emission for low-loss optical waveguide and optical logic gate

The luminescence color of molecule-based photoactive materials is the key to the applications in lighting and optical communication.Realizing continuous regulation of emission color in molecular systems is highly desirable but still remains a challenge due to the individual emission band of purely organic molecules.Herein,a novel alloy strategy based on molecular co-crystals is reported.By adjusting the molar ratio of pyrene(Py)and fluorathene(Flu),three types of molecular co-crystal alloys(MCAs)assemblies are prepared involving Py-Flu-OFN-x%,Py-Flu-TFP-x%,Py-Flu-TCNB-x%.Multiple energy level structure and Förster resonance energy transfer(FRET)process endow materials with tunable full-spectra emission color in visible region.Impressively,these MCAs and co-crystals can be successfully applied to low optical loss waveguide and optical logic gate by virtue of all-color luminescence from blue across green to red,together with smooth surface of onedimensional microrods,which show promising applications as continuous light emitters for advance photonics applications.

Crystal Structures of Bis[aquachlorotriphenyltin(Ⅳ)] dihydrate·1,4,7,10,13,16-hexacyclooctadecane bis[aquachlorotriphenyltin(Ⅳ)]·1,4,7,10,13,16-hexacyclooct-adecane(3/1) and Bis[aquatrifluoroacetatotriphenyltin(Ⅳ)] dihydrate·1,4,7,10,13,16-hexa

In the crystal structures of the centrosymmetric isostructural co-crystals, bis[aqua- hlorotriphenyltin]dihydrate1,4,7,10,13,16-hexacyclooctadecane-bis[aquachlorotriphenyltin(Ⅳ)] 1,4,7,10,13,16-hexacyclooctadecane (3/1) 1 and bis[aquatrifluoroacetatotriphenyltin] dihydrate 1,4,7,10,13,16-hexacyclooctadecane-bis[aquatrifluoroacetatotriphenyltin(IV)]1,4,7,10,13,16- hexacyclooctadecane(3/1) 2, the crown ether interacts with the triphenyltin unit through both the coordinated and lattice water molecules in one molecular entity, but only through the coordinated water molecule in the other. The tin atoms are five-coordinate in trans-trigonal bipyramidal environments. Compound 1 is refined on 204 variables and 4665 I > 3s(I) reflections to R = 0.055, and compound 2 on 233 variables and 5721 I > 3s(I) reflections to R = 0.052. For crystal 1: C192H244Cl8O38Sn8, fw = 4392.99, trigonal, R3, a = 27.391(1), c = 23.007(1) ? V = 14948(1) ?, Z = 3, Dc = 1.464 g/cm3, F(000) = 6708 and m = 1.162 mm-1; and for 2: C208H244F24O54Sn8, fw = 5013.55, trigonal, R3, a = 28.775(1), c = 23.289(1) ? V = 16699(1) 3, Z = 3, Dc = 1.496 g/cm3, F(000) = 7620 and m = 0.978 mm-1.

Synthesis,Structure and Photoluminescence of Cocrystal of Bis[2-(benz(oxa/imida)zol-2-yl)phenolato-к~2N,O]zinc(Ⅱ) Being Site Occupancy Disorder with a Heteroatom Ratio of NH to O(0.408/0.592)

The zinc（Ⅱ） complex with Hpbx （Hpbx = 2-（benzoxazol-2-yl）phenol） and Hpbm （Hpbm = 2-（benzimidazol-2-yl）phenol）, namely [Zn（pbm）2]1.633[Zn（pbx）212.367·DMF·2H2O 1, has been synthesized and characterized by X-ray crystallography, FTIR and elemental analysis. The coordination structures are statistically disordered and can be regarded as a co-crystal of [Zn（pbm）2] and [Zn（pbx）2] with the ratio of ca. 0.408/0.592. Solvate water and DMF molecules are also present in the lattice. Crystal data for 1; monoclinic, space group P21/c, Mr= 2049.02, Z = 2, α = 9.7571（6）, b = 25.6415（16）, c = 19.8675（10） A, β= 111.342（2）°, V = 4629.7（5） A^3, Dc = 1.470 g/cm^3,μ = 1.100 mm^-1, F（000） = 2104, R = 0.0575 and wR = 0.1282 for 5528 observed reflections （I〉2σ（I））. The photoluminescent spectra for this compound have also been studied.

Structural Study on Four co-Crystals of N-Containing Heteroaromatics with Iodofluorobenzene

N-Containing heteroaromatics 1,2,4,5-tetra（pyridin-3-yl）benzene[1,2,4,5-T（3-PY）B] and 1,2,4,5-tetra（pyridin-4-yl）benzene[1,2,4,5-T（4-PY）B] were each co-crystallized with 1,2-diiodo-tetrafluoro-benzene（1,2-DITFB）, or 1,4-diiodo-tetrafluoro-benzene（1,4-DITFB）, respectively, generating four co-crystals, namely, （1,2-DITFB）4 [1,2,4,5-T（3-PY）B]（1）, （1,2-DITFB）4.[ 1,2,4,5-T（4-PY）B]（2）, （1,4-DITFB）2.[1,2,4,5-T（3-PY）B]-CHCI3（3）, and （1,4-DITFB）-[1,2,4,5-T（4-PY）B]2CHCI3（4）. This study takes aim at providing an insight into the relative importance of fundamental solid state halogen bonding interactions（i.e., halogen..N, halogen,..halogen, and halogen...π in systems. The effects of the donor and acceptor on supramolecular assembly and the crystal structure determined interactions were discussed. The N...I halogen bonds are the main directing interactions responsible for the observed structures. In compounds 1 and 2, the donors exhibited lower-than-expected supramolecular connectivity. In spite of this, co-crystal 2 exhibits polymeric structures consisting of infinite one-dimensional（1D） double-zigzag chains of alternating electron donor and acceptor. The basic structure of co-crystals 3 and 4 is also infinite 1D chain. Therefore, the ID halogen bonded supramolecular assemblies can be obtained by matching the appropriate donor and acceptor.

Co-crystals of non-steroidal anti-inflammatory drugs(NSAIDs):Insight toward formation,methods,and drug enhancement

Pharmaceutical co-crystals have been explored by many researchers as a strategy to optimize physicochemical properties of solid-state drugs.Their improvements of solubility,bioavailability,and the reduced tendency for phase transformation occurrence,are factors that highlight benefits of pharmaceutical co-crystals among other solid forms.According to the Biopharmaceutical Classification System(BCS),non-steroidal anti-inflammatory drugs(NSAIDs)are class Ⅱ drugs,which have low aqueous solubility and therefore co-crystallization has the potential to optimize NSAID product properties.In this review,we highlight the recent progress made on NSAIDs co-crystals,their co-formers,synthesis,methods and use,while we underline some promising results on in vitro and in vivo co-crystal properties.A celecoxib-tramadol co-crystal reaches phase Ⅲ clinical trials,showing greater analgesic activity than both individual APIs.The aqueous solubility of the co-crystal formed between l-proline and diclofenac is very high in comparison with the pure drug.Naproxen co-crystals with urea and thiourea have an increase of drug release of almost 60%.Co-crystal design brings a new perspective in drug development since the co-former used can also be a biologically active component allowing to combine different anti-inflammatory drugs,which have an incredible spectrum of application due to the analgesic,anti-pyretic and anti-inflammatory properties.

Synthesis, Crystal Structures, Hirshfeld Surfaces, Thermo Characteristics and Solubility of Co-crystal of Buprofezin with Hydrofluoric Acid

A new kind of co-crystal of buprofezin(C(16)H(24)FN3OS) with hydrofluoric acid has been prepared through evaporation technique. It crystallizes in the triclinic space group P1, with a = 9.9733(8), b = 10.3460(9), c = 10.5739(12) ?, a = 68.655(9), b = 73.291(9), g = 66.738(8)o, V = 920.34(17) ?~3, Mr = 325.44, Dc = 1.174 g/cm^3, Z = 2, F(000) = 348, m = 0.190 mm^(-1), the final GOOF = 1.042, R = 0.0485 and wR = 0.1167. Single-crystal X-ray diffraction, XRPD, DSC, TGA, Hirshfeld surface analysis, Raman spectroscopy and FT-IR were used to characterize the co-crystal. It has a twodimensional plane structure, and the intermolecular interactions of co-crystal are mainly H–F×××H, H–O×××H and H–O×××H. Thermology study further confirmed that co-crystal has stronger thermal stability and higher melting point than buprofezin, and it has stronger water solubility. The results show that this co-crystal is valuable for the study of residual activity and application effects of buprofezin.

Crystal Engineering of Multiple-component Organic Compound： Organic co-Crystals of the Functional Groups of Carboxyl and Amino with Persistent Hydrogen Bonding Motifs

Three small organic molecular co-crystal compounds （C3N6H6）·（C6H10O4）·H2O（I）, C3HsN2O（3） and （H4btec）2.（4,4＇-bipy）（4）（H4btec=1,2,4,5-benzenetetracarboxylic acid, 4,4＇-bipy=4,4＇-bipyridine） and one coordination supramolecular compound [Mn（CEO4）（HEO）E]＇C6HllNO2（2） were synthesized by hydrothermal reaction. They were characterized by elemental analysis, infrared（IR） spectroscopy and single crystal X-ray diffraction（XRD）. Structural analyses reveal that these 2D or 3D supramolecular networks of the compounds were formed by C--H…O, N--H…O, N--H…N, O--H…O and O-H…N hydrogen bonds. Therein, the functional groups of--COOH, --NH2 and --OH play important roles in constructing supramolecular architectures.

Pressure-induced Diels-Alder reactions in C_6H_6—C_6F_6 Co-crystal towards graphane structure

With support from the National Natural Science Foundation of China and the Top 1000-Talents Awards,the research team led by Dr.Zheng HaiYan(郑海燕)and Dr.Li Kuo(李阔)from the Center for High Pressure Science and Technology Advanced Research in Beijing recently synthesized H-F-substituted graphane(H,F-graphane)with a layered structure by compressing 1:1 C6H6-C6F6 co-crystal(abbreviated as CHCF).

Rational design and crystallographic analysis of novel isoform-selective TRKA inhibitors for cancer therapy

To the Editor:Tropomyosin receptor kinase A/B/C(TRKA/B/C)are encoded by neurotrophic tyrosine receptor kinase 1/2/3(NTRK1/2/3),respectively.NTRK gene fusions are the most common drivers of malignancies.Additionally,TRKA is the most common oncogene in TRK family,which is detected in 7.4%of human tumors.

Distinctive Polymorphism-like Isodimorphism in Poly(propylene succinate-ran-propylene fumarate)

Co-crystallization of different monomeric units fundamentally contributes to the versatile and tunable performance of random copolymers.At present,the crystallization manners of random binary copolymers have been divided into three categories:isomorphism,isodimorphism and comonomer exclusion.Each category,however,has its own advantages and disadvantages.Therefore,it is challenging to design and prepare random copolymer sharing the advantages of isomorphism and isodimorphism through a new co-crystallization manner beyond the ones already exist.On the basis of previous study on poly(alkylene succinate-ran-alkylene fumarate)whose co-crystallization can be extensively and finely regulated by simply varying the chemical structure of alkylene,random copolymers of poly(propylene succinate-ranpropylene fumarate)(PPSF)are synthesized using 1,3-propanediol as the diol source.The thermal properties and crystal structure of PPSF are investigated,and,intriguingly,it is proved that PPSF is an isodimorphism system while displays similar composition-dependent thermal properties and crystallinity as isomorphism.That is,PPSF exhibits a novel co-crystallization behavior that has rarely been discovered,which would combine the advantages of both isomorphism and isodimorphism.Consequently,PPSF could be termed as a new-type,special compositiondependent polymorphism.Besides,the altering of PPS-like to PPF-like crystal structure of PPSF when changing chain composition has been proved to originate from the shift of dominant inter-segment interaction from van der Waals forces to strong hydrogen-bonding interaction.This work enriches the co-crystallization manner of random copolymers,leading to more diverse performance design of polymer materials.

Novel phthalimides regulating PD-1/PD-L1 interaction as potential immunotherapy agents

Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1)have emerged as one of the most promising immune checkpoint targets for cancer immunotherapy.Despite the inherent advantages of small-molecule inhibitors over antibodies,the discovery of small-molecule inhibitors has fallen behind that of antibody drugs.Based on docking studies between small molecule inhibitor and PD-L1 protein,changing the chemical linker of inhibitor from a flexible chain to an aromatic ring may improve its binding capacity to PD-L1 protein,which was not reported before.A series of novel phthalimide derivatives from structure-based rational design was synthesized.P39 was identified as the best inhibitor with promising activity,which not only inhibited PD-1/PD-L1 interaction(IC_(50)=8.9 nmol/L),but also enhanced killing efficacy of immune cells on cancer cells.Co-crystal data demonstrated that P39 induced the dimerization of PD-L1 proteins,thereby blocking the binding of PD-1/PD-L1.Moreover,P39 exhibited a favorable safety profile with a LD_(50)>5000 mg/kg and showed significant in vivo antitumor activity through promoting CD8^(+)T cell activation.All these data suggest that P39 acts as a promising small chemical inhibitor against the PD-1/PD-L1 axis and has the potential to improve the immunotherapy efficacy of T-cells.