Atropisomeric Phosphine Ligands Bearing C-N Axial Chirality: Applications in Enantioselective Suzuki-Miyaura Cross-Coupling Towards the Assembly of Tetra-ortho-Substituted Biaryls.

Biaryl phosphines bearing C(Ar)-C(Ar) axial chirality are commonly known and have been successfully applied in many asymmetric catalyses. Nevertheless, the development of a chiral ligand having an axially chiral C(Ar)-N backbone remains elusive due to its undesirable less restricted rotational barrier. In fact, it is highly attractive to overcome this challenge in ligand development as the incorporation of an N-donor component at the chiral axis is more favorable toward the transient metal coordination, and thus, a better outcome of stereocommunication is anticipated to the approaching substrates. Herein, we present a rational design of a new collection of chiral phosphines featuring a C-N axial chirality and their applications in enantioselective Suzuki-Miyaura cross-coupling for accessing highly steric hindered tetra-ortho-substituted biaryls (26 examples up to 98:2 er). It is worth noting that the embodied carbazolyl framework is crucial to succeed the reaction, by the fruitful steric relief of bulky substrate coordination and transmetalation via a fleeting Pd-N jumping to Pd-π fashion. DFT calculation reveals an interesting Pd-arene-walking characteristic across the carbazolyl plane for attaining a lower energy-preferred route in a catalytic cycle. The theoretical study successfully predicts the stereooutcome and matches the enantioselectivity with the experimental results.

Enantioselective synthesis of chiral heterocyclic biaryls via asymmetric Suzuki-Miyaura cross-coupling of 3-bromopyridine derivatives.

A series of chiral heterocyclic biaryls with a pyridyl moiety were prepared in moderate to good yields with up to 92% ee via asymmetric Suzuki-Miyaura coupling. The chiral-bridged biphenyl monophosphine ligand L1 was found to be much more effective in the reaction enantioselection than its counterpart binaphthyl monophosphine ligands.

The experimental study of shunt-decompression arterialized vein flap.

BACKGROUND: Arterialized vein flap is a kind of unphysiological flap. Unphysiological reconstruction of blood circulation leads to higher load than that supported by physiological flap and is the culprit of flap swelling, blood stasis, skin blistering, and necrosis after flap grafting. To resolve the multiple disadvantages of traditional flap grafting, by introducing the principles of fluid mechanics, shunt-decompression surgery is prepared to decline the circulation preload and improve the prognosis of arterialized vein flap grafting. METHODS: By introducing the principles of fluid mechanics, we established the model of shunt-decompression arterialized vein flap, which satisfied the common properties of general fluid that the interface pressure between object and fluid is reduced when the velocity of fluid is increased and vice versa-the effect of Bernoulli. Under this rule, we anastomose the arterialized vein to the branch of main artery of recipient region or make end-to-side anastomosis, which can maintain the blood flow of main artery, decrease the perfusion of flap, and preserve the decompressive effect of main artery to branches. From March, 2016 to September, 2016, we performed animal experiments on ten male bama mini pigs with average weight of 28 ± 2.35 kg. Superior epigastric artery of pig was used for feeding artery to arterialize the superficial epigastric veins. The total area of flap is 8 cm × 6 cm. End-to-side anastomosis and end-to-end anastomosis were established in experimental group and control group, respectively. Doppler speckle perfusion imaging apparatus was used to monitor the alterations of flap perfusion, blood flow of flap, tissue swelling and survival of flaps. RESULTS: The average flap perfusion (PU) at 1 week after surgery is 83.62 ± 3.14 in experimental group and 98.14 ± 6.54 in control group, respectively (P < 0.05), indicating the significant reduction of flap blood perfusion in experimental group as compared with control group. As to the survival of flaps, 7 flaps completely survived, 3 showed partial necrosis, and no one was found as complete necrosis in experimental group, while only 3 flaps survived, and 4 flaps and 3 flaps showed partial necrosis and complete necrosis in control group, respectively (P < 0.05). CONCLUSION: Based on the physiological features of arterialized vein flap and its problems in clinical application, we improved the anastomosis strategy of flap grafting and obtained excellent experimental outcomes, which provides an insight for the clinical application of arterialized vein flaps.

New Family of Octagonal-Prismatic Lanthanide Coordination Cages Assembled from Unique Ln17 Clusters and Simple Cliplike Dicarboxylate Ligands.

Novel high-nuclearity lanthanide clusters (Ln17) are generated in situ in the coordination-driven self-assembly. A metal-cluster-directed symmetry strategy for building metal coordination cages is successfully applied to a lanthanide system for the first time. A new family of octagonal-prismatic lanthanide coordination cages UJN-Ln, formulated as [Ln(µ3-OH)8][Ln16(µ4-O)(µ4-OH)(µ3-OH)8(H2O)8(µ4-dcd)8][(µ3-dcd)8]·22H2O (Ln = Gd, Tb, Dy, Ho, and Er; dcd = 3,3-dimethylcyclopropane-1,2-dicarboxylate dianion), have been assembled from the unique Ln17 clusters and simple cliplike ligand H2dcd. Apart from featuring aesthetically charming structures, all of the compounds present predominantly antiferromagnetic coupling between the corresponding lanthanide ions. Additionally, the intense-green photoluminescence for UJN-Tb and magnetic relaxation behavior for UJN-Dy have been observed. Remarkably, UJN-Gd shows a large magnetocaloric effect (MCE) with an impressive entropy change value of 42.3 J kg(-1) K(-1) for ΔH = 7.0 T at 2.0 K due to the high-nuclearity cluster and the lightweight ligand. The studies highlight the structural diversity of multigonal-prismatic metal coordination cages and provide a new direction in the design of cagelike multifunctional materials by the introduction of lanthanide clusters and other suitable cliplike ligands.

[Identification of Official Rhubarb Samples by Using PLS and Terahertz Time-Domain Spectroscopy].

The development of terahertz technology is attracting broad intention in recent years. The quality identification is important for the quality control of Chinese medicine production. In the present work, terahertz time-domain spectroscopy (THz-TDS) combined with partial least squares (PLS) were used for the identification model building and studied based on 41 official and unofficial rhubarb samples. First, the THz-TDS spectra of rhubarb samples were collected and were preprocessed by using chemometrics methods rather than transformed to absorption spectra. The identification models were then established based on the processed terahertz time domain spectra. The spectral preprocessing methods include Savitzky-Golay (S-G) first derivative, detrending, standard normal transformation (SNV), autoscaling, and mean centering. The identification accuracy of 90% was accomplished by using proper pretreatment methods, which was higher than the classified accuracy of 80% without any preprocessing for the time domain spectra. The component number of the PLS model was evaluated by leave-one-out cross-validation (LOOCV). The minimum values of the root-mean squared error of cross-validation (RMSECV) and root-mean squared error of prediction (RMSEP) were 0.076 6 and 0.169 0 by using mean centering method, respectively. The results of this work showed that the combination of terahertz time domain spectroscopy technology with chemometrics methods, as well as PLS can be applied for the recognition of genuine and counterfeit Chinese herbal medicines, as well as official and unofficial rhubarbs. The advantage of using terahertz time domain spectra directly with no transformation into absorption spectra is: (1) the thickness of samples could not be considered in the model establishment, and (2) the spectral processing was simplified. The proposed method based on the combination of THz-TDS and chemometrics proved to be rapid, simple, non-pollution and solvent free, suitable to be developed as a promising tool for quality control of many other Chinese herbal medicines.

[The Study on the Far-FTIR and THz Spectra of Azitromycin Drugs with Different Physical Forms].

Far Fourier transform infrared spectroscopy (Far-FTIR) and terahertz time-domain spectroscopy (THz-TDS) were used to measure the fingerprint spectra of Azitromycin suspension, capsule, tablet and dispersible tablet under vacuum and nitrogen conditions, respectively. In the frequency range of 0.2-15 THz, highly resolved spectral features for Azitromycin suspension were measured and some minor differences were observed between domestic and exotic Azitromycin Suspension, such as linewidth broadening and additional peaks. As same time, for the domestic Azitromycin capsule, tablet and dispersible tablet, the absorption baselines in the range of 0.2-2.7 THz rise with the increase of frequency while absorption peaks become weaker due to the scattering of bigger particles and smaller amount of Azitromycin. Also, the additional peaks are caused by the absorption of filling materials. In parallel with the qualitative measurement, the THz absorption spectra for mixtures of polyethylene (PE) powders and exotic Azithomycin suspension with different concentrations were also measured. According to the linear correlation between the concentration and the absorption intensity, the concentration of effective component can be evaluated accurately. This means that THz-TDS method is suitable for the quality inspection and evaluation of the mixed Azithromycin system.

Anhydrous lanthanide MOFs and direct photoluminescent sensing for polyoxometalates in aqueous solution.

New anhydrous lanthanide metal-organic frameworks (MOFs) [Pr(tip)1.5]2n (tip-Pr), [Nd(tip)1.5]2n (tip-Nd), [Eu-(tip)1.5]2n (tip-Eu), and [Eu(OH)(mip)]n (mip-Eu) (tip=5-tert-butylisophthalate anion, mip=5-methylisophthalate ion), have been hydrothermally synthesized and structurally characterized by elemental analyses, FT-IR spectroscopy, single-crystal X-ray diffraction, thermal gravimetric analysis/differential thermal analysis (TG/DTA), and X-ray powder diffraction (XRPD) techniques. MOFs tip-Pr, tip-Nd, and tip-Eu are isostructural anhydrous compounds, and exhibit an unprecedented 3D microporous structure with hexagonal channel arrays. The selectively prepared MOF mip-Eu presents an interpenetrated 3D microporous architecture containing the hydroxyl cluster chains. Solid-state photoluminescence properties at room temperature indicate that both tip-Eu and mip-Eu display the characteristic of the Eu3+ ion spectrum dominated by the 5D0-->7F(J) (J=0-4) transition. Compared with mip-Eu, tip-Eu displays the very high solid-state quantum yield (0.62 ± 0.03) and longer lifetime value (0.94 ± 0.01 ms), which is due to the absence of the hydroxyl groups from the solid-state structure of tip-Eu. More importantly, a new method to directly investigate the potential of solid-state lanthanide MOFs for ionic sensing in aqueous solutions has been developed, and successfully applied it to study the potential sensing function of tip-Eu for polyoxometalates (POMs). The possible mechanism for the quenching effect of POMs on the fluorescence of tip-Eu is elucidated by the strongly competitive absorption of the excited light source energy between POMs and tip ligands. The very promise for the highly sensitive sensing for polyoxometalates, together with the characteristic of the reversible fluorescence response, suggest that solid-state tip-Eu can be an excellent candidate for the directly photoluminescent detection of POMs in aqueous solutions.

DBU-catalyzed diastereoselective 1,3-dipolar [3+2] cycloaddition of trifluoroethyl amine-derived isatin ketimines with chalcones: synthesis of 5'-CF3-substituted 3,2'-pyrrolidinyl spirooxindoles.

A diastereoselective 1,3-dipolar cycloaddition reaction between trifluoroethyl amine-derived isatin ketimines and chalcones was successfully achieved in the presence of DBU. A series of 5'-CF3-substituted 3,2'-pyrrolidinyl spirooxindoles were efficiently synthesized with high yields and excellent diastereoselectivities (up to 89% yield, and >99 : 1 dr). The in vitro anticancer activities of these highly functionalized spiro[pyrrolidin-3,2'-oxindole] derivatives were evaluated.

Squaramide-catalyzed enantioselective Michael addition of nitromethane to 2-enoylazaarenes: synthesis of chiral azaarene-containing γ-nitroketones.

Bifunctional chiral squaramide-catalyzed highly enantioselective Michael addition of nitromethane to diverse 2-enoylazaarenes was successfully performed. This protocol provided a set of chiral azaarene-containing γ-nitroketones with up to 98% yield and 98% ee in a solvent-free catalytic system under mild conditions. Furthermore, gram-scale synthetic utility was also showcased.

Dehydroabietane-type bifunctional organocatalysts in asymmetric synthesis: recent progress.

Dehydroabietane-type bifunctional organocatalysts derived from rosane-type diterpenes of dehydroabietic acid (DHAA) and dehydroabietylamine (DA) have been utilized in a wide variety of highly enantioselective reactions. Since one well-documented review exclusively reported on the development of terpene-derived bifunctional thioureas in asymmetric organocatalysis in 2013, fragmentary progress on the dehydroabietane-type bifunctional thioureas and squaramides has been mentioned in other reviews. In this mini-review, we systematically analyze and reorganize the published literature on dehydroabietane-type bifunctional organocatalysts in the recent decade according to the type of catalysts. Our aim is for this review to provide helpful research information and serve as a foundation for further design and application of rosin-based organocatalysts.

Acoustic vibration sensor based on nonadiabatic tapered fibers.

A simple and low-cost vibration sensor based on single-mode nonadiabatic fiber tapers is proposed and demonstrated. The environmental vibrations can be detected by demodulating the transmission loss of the nonadiabatic fiber taper. Theoretical simulations show that the transmission loss is related to the microbending of the fiber taper induced by vibrations. Unlike interferometric sensors, this vibration sensor does not need any feedback loop to control the quadrature point to obtain a stable performance. In addition, it has no requirement for the coherence of the light source and is insensitive to temperature changes. Experimental results show that this sensing system has a wide frequency response range from a few hertz to tens of kilohertz with the maximal signal to noise ratio up to 73 dB.

[High-resolution THz spectra of six biological and pharmaceutical materials].

The temperature dependent vibrational spectra of,three biological and pharmaceutical sets, genistein and biochanin A, clenbuterol hydrochloride and salbutamol, as well as ginseng R2 and R3, in the range of 0.2-4.5 THz (6.6-150.0 cm(-)) are presented over the temperature range from 295 to 77 K Although there are only some minor difference in their molecular structures, the spectra of two samples in every group are quite differences in both absorption band positions and their relative intensities, and display strong linewidth narrowing and frequency blue-shift with cooling. Au 77 K, 13 highly resolved spectral features for biochanin A were obtained and the sensitivity of the experiment allows detection of amounts as small as 1.9 x 10(-5) mol of ginseng R3. Such high-resolution THz fingerprint spectra provide a rapid, nondestructive and reliable method for the identification of these pharmaceutical settings molecules.

[Far-IR and THz absorption spectra studies of metronidazole, tinidazole and ornidazole].

Metronidazole, tinidazole and ornidazole are 5-nitro-imidazole medicines used particularly for anaerobic bacteria and protozoa infections. The present paper reports that terahertz time-domain spectroscopy (THz-TDS) and Fourier transform infrared spectroscopy (Far-FTIR) were used to measure the fingerprint spectra of metronidazole, tinidazole and ornidazole in the frequency range of 0.9 - 19.5 THz under the room temperature. In addition, THz-TDS was also used to measure the absorption spectra of pure tinidazole and tinidazole tablets from different manufactures between 0.2 and 2.2 THz. In parallel with the experimental study, the cross correlation analysis was applied to compare the array of correlation coefficients between pure tinidazole and different tinidazole tablets. Results show that the method is rapid, simple and accurate to identify their effective chemical compositions and stability when the FTIR and THz spectra data combine with the array of correlation coefficient. Our research provides a visual approach to the standardization and modernization of the quality control in the production and sale of such drugs.

[Evaluation of walnut by terahertz nondestructive technology].

The deterioration and shell thickness of walnut were studied using the terahertz time domain spectroscopy. Firstly, the THz spectra of moth-eaten, moldy and normal walnuts were compared, and the bad walnuts were properly rejected due to the differences of absorption peaks. Secondly, the transmission-type and reflection-type terahertz time domain spectroscopy system was used simultaneously, and a new formula to calculate shell thickness of walnut was built in the THz system. Then the authors measured the shell thickness based on the detectable refractive index of walnut, and the relative error was 3.7%. Consequently, the quality of walnut was evaluated nondestructively according to physical and chemical indicators from walnut THz spectra respectively.

[Optimization of the extraction process for qingrejiedu oral liquid with synthesizing multiple guidelines grading method].

OBJECTIVE: To optimize the extraction process for Qingrejiedu oral liquid with synthesizing multiple guidelines grading method. METHODS: Used the extraction rate of baicalin and geniposide comprehensive contribution rate variance as index, extraction time and added water were as factors, central composite design was used for optimization of extraction process, and forecasting analysis parameters. RESULTS: The optimal extraction process was as follows: extraction time 139 min, added water 13 times, grading index was 0.768. CONCLUSION: Synthesizing multiple guidelines grading method is ideal for multi-component extraction experiment design, its easy application, the forecast is good and so on.

[Optimal extraction of puerarin from Pueraria lobata based on central composite design and response surface methodology].

OBJECTIVE: To optimize the parameters of extraction technology for Puerarin from Pueraria lobata by Central Composite Design-Response Surface Methodology. METHODS: Used the ratio of dosage liquid and extraction time as the examination factor,the content of puerarin for the extraction percentage as the index. The multielement linear model and the polynomial model were used to describe the mathematics relation with response surface. RESULTS: The optimal extraction technology was as follows: ratio of herb-to-solvant was 1: 8.88 (W/V) and extraction time was 150 min. The coefficient correlation was 0.9977 and closed to the predicted value. CONCLUSION: The results are accordant with model predictions. The technology can be used as the extraction process of puerarin from Pueraria lobata.

Prevalence, Risk Factors, and Psychological Effects of Overactive Bladder in Chinese University Students.

PURPOSE: The purpose of this study was to investigate the prevalence and risk factors of overactive bladder (OAB) in young adults and to explore the influence of OAB on mental health. METHODS: Between October 2019 and January 2020, 14,010 anonymous questionnaires were distributed to freshmen at 2 universities in Henan, China. The students came from all over the country. The questionnaire included general items and information necessary to calculate the overactive bladder symptom score, the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) score, Self-Esteem Scale (SES) score, and Self-Rating Depression Scale (SDS) score. The relationships between the prevalence of OAB and its risk factors were evaluated. RESULTS: The overall prevalence of OAB was 6.0%, with 4.3% of participants characterized as having dry OAB and 1.7% as having wet OAB. The prevalence of mild OAB was 5.5%, and that of moderate OAB was 0.5%; no severe OAB was observed. Higher prevalence rates of OAB were found among women, respondents with constipation, and respondents with primary nocturnal enuresis (PNE) (P <0.05). Compared to healthy controls, the OAB group exhibited a higher mean SDS score (52.12±8.986 vs. 47.71±9.399, P<0.001) and mean PSQI score (5.28±2.486 vs. 4.27±2.431, P<0.001), but a lower mean SES score (27.78±3.599 vs. 29.57±4.109, P<0.001). CONCLUSION: OAB significantly affects the mental health of young adults. Female sex, constipation, and PNE are risk factors for OAB.

Interpenetrated metal-organic frameworks with enhanced photoluminescence for selective recognition of m-xylene from xylene isomers.

Two novel luminescent metal-organic frameworks (MOFs), [Zn3(TCA)2(BPB)2]n (DZU-101, where H3TCA = 4,4',4''-tricarboxyltriphenylamine and BPB = 1,4-bis(pyrid-4-yl)benzene) and [Zn3(TCA)2(BPB)DMA]n (DZU-102), based on the same ligands and metal ions were synthesized by regulating the amount of water in the solvothermal reaction system. Structural analyses show that the two MOFs have pillar-layered frameworks with Zn3 clusters connected by the TCA3- and BPB ligands. Interestingly, DZU-102 possessed a two-fold interpenetrated framework distinct from the individual network of DZU-101. As a result, DZU-102 showed a visual fluorescence color change from chartreuse to azure in m-xylene, while the fluorescence color was turquoise in p-/o-xylene with no change. Furthermore, compared with p/o-xylene, the fluorescence emission peak of DZU-102 in m-xylene suspension produced an obvious blue shift. Moreover, selective fluorescence sensing experiments were also carried out, which demonstrated that the degree of peak shift was related to the concentration of m-xylene, indicating the potential application of DZU-102 in fluorescence sensing of m-xylene from xylene isomers and further revealed the application of structural interpenetration for luminescence tuning of MOFs.

Structure and photoluminescence tuning features of Mn(2+)- and Ln(3+)-activated Zn-based heterometal-organic frameworks (MOFs) with a single 5-methylisophthalic acid ligand.

In attempts to investigate whether the photoluminescence properties of the Zn-based heterometal-organic frameworks (MOFs) could be tuned by doping different Ln(3+) (Ln = Sm, Eu, Tb) and Mn(2+) ions, seven novel 3D homo- and hetero-MOFs with a rich variety of network topologies, namely, [Zn(mip)](n) (Zn-Zn), [Zn(2)Mn(OH)(2)(mip)(2)](n) (Zn-Mn), [Mn(2)Mn(OH)(2)(mip)(2)](n) (Mn-Mn), [ZnSm(OH)(mip)(2)](n) (Zn-Sm), [ZnEu(OH)(mip)(2)](n) (Zn-Eu1), [Zn(5)Eu(OH)(H(2)O)(3)(mip)(6)·(H(2)O)](n) (Zn-Eu2), and [Zn(5)Tb(OH)(H(2)O)(3)(mip)(6)](n) (Zn-Tb), (mip = 5-methylisophthalate dianion), have been synthesized hydrothermally based on a single 5-methylisophthalic acid ligand. All compounds are fully structurally characterized by elemental analysis, FT-IR spectroscopy, TG-DTA analysis, single-crystal X-ray diffraction, and X-ray powder diffraction (XRPD) techniques. The various connectivity modes of the mip linkers generate four types of different structures. Type I (Zn-Zn) is a 3D homo-MOF with helical channels composed of Zn(2)(COO)(4) SBUs (second building units). Type II (Zn-Mn and Mn-Mn) displays a nest-like 3D homo- or hetero-MOF featuring window-shaped helical channels composed of Zn(4)Mn(2)(OH)(4)(COO)(8) or Mn(4)Mn(2)(OH)(4)(COO)(8) SBUs. Type III (Zn-Sm and Zn-Eu1) presents a complicated corbeil-like 3D hetero-MOF with irregular helical channels composed of (SmZnO)(2)(COO)(8) or (EuZnO)(2)(COO)(8) heterometallic SBUs. Type IV (Zn-Eu2 and Zn-Tb) contains a heterometallic SBU Zn(5)Eu(OH)(COO)(12) or Zn(5)Tb(OH)(COO)(12), which results in a 3D hetero-MOF featuring irregular channels impregnated by parts of the free and coordinated water molecules. Photoluminescence properties indicate that all of the compounds exhibit photoluminescence in the solid state at room temperature. Compared with a broad emission band at ca. 475 nm (λ(ex) = 380 nm) for Zn-Zn, compound Zn-Mn exhibits a remarkably intense emission band centered at 737 nm (λ(ex) = 320 nm) due to the characteristic emission of Mn(2+). In addition, the fluorescence intensity of compound Zn-Mn is stronger than that of Mn-Mn as a result of Zn(2+) behaving as an activator for the Mn(2+) emission. Compound Zn-Sm displays a typical Sm(3+) emission spectrum, and the peak at 596 nm is the strongest one (λ(ex) = 310 nm). Both Zn-Eu1 and Zn-Eu2 give the characteristic emission transitions of the Eu(3+) ions (λ(ex) = 310 nm). Thanks to the ambient different crystal-field strengths, crystal field symmetries, and coordinated bonds of the Eu(3+) ions in compounds Zn-Eu1 and Zn-Eu2, the spectrum of the former compound is dominated by the (5)D(0) → (7)F(2) transition (612 nm), while the emission of the (5)D(0) → (7)F(4) transition (699 nm) for the latter one is the most intense. Compound Zn-Tb emits the characteristic Tb(3+) ion spectrum dominated by the (5)D(4) → (7)F(5) (544 nm) transition. Upon addition of the different activated ions, the luminescence lifetimes of the compounds are also changed from the nanosecond (Zn-Zn) to the microsecond (Zn-Mn, Mn-Mn, and Zn-Sm) and millisecond (Zn-Eu1, Zn-Eu2, and Zn-Tb) magnitude orders. The structure and photoluminescent property correlations suggest that the presence of Mn(2+) and Ln(3+) ions can activate the Zn-based hetero-MOFs to emit the tunable photoluminescence.

[Synthesis and spectral characteristic of pharmaceutical dipfluzine hydrochloride-benzoic acid co-crystal].

Pharmaceutical co-crystals can improve the chemical and physical properties of active pharmaceutical ingredient (API), which is new idea and expected to provide new stable structures. Pharmaceutical co-crystals have the potential to be much more useful in pharmaceutical products than salts, solvates or hydrates, polymorphs and stoichiometric solvates (pseudo-polymorphs). In our study, dipfluzine hydrochloride-benzoic acid co-crystal was synthesized by solid co-grinding. The samples were subjected to IR, DSC, XRD, Raman and THz spectral analysis. The results indicated that dipfluzine hydrochloride-benzoic acid complex was new phase compared with the single API and CCF. THz-TDS characterization indicated that hydrogen bond formed between API and CCF, which confirmed the formation of co-crystal.