Molecules 1a Research Articles

Synthesis and Spectroscopic Characterization of Selected Phenothiazines and Phenazines Rationalized Based on DFT Calculation.

Two unique structures were isolated from the phosphorylation reaction of 10H-phenothiazine. The 5,5-dimethyl-2-(10H-phenothiazin-10-yl)-1,3,2-dioxaphosphinane 2-oxide (2a) illustrates the product of N-phosphorylation of phenothiazine. Moreover, a potential product of 2a instability, a thiophosphoric acid 2b, was successfully isolated and structurally characterized. Molecule 2a, similarly to sulfoxide derivative 3, possesses interesting phosphorescence properties due to the presence of d-pπ bonds. The X-ray, NMR, and DFT computational studies indicate that compound 2a exhibits an anomeric effect. Additionally, the syntheses of selected symmetrical and unsymmetrical pyridine-embedded phenazines were elaborated. To compare the influence of phosphorus and sulfur atoms on the structural characteristics of 10H-phenothiazine derivatives, the high-quality crystals of (4a,12a-dihydro-12H-benzo[5,6][1,4]thiazino[2,3-b]quinoxalin-12-yl)(phenyl)methanone (1) and selected phenazines 5,12-diisopropyl-3,10-dimethyldipyrido[3,2-a:3',2'-h]phenazine (5) and 5-isopropyl-N,N,3-trimethylpyrido[3,2-a]phenazin-10-amine (6a) were obtained. The structures of molecules 1, 2a, 2-mercapto-5,5-dimethyl-1,3,2-dioxaphosphinane 2-oxide (2b), 3,7-dinitro-10H-phenothiazine 5-oxide (3), 5 and 6a were determined by single-crystal X-ray diffraction measurements.

Novel nitrogen mustard-artemisinin hybrids with potent anti-leukemia action through DNA damage and activation of GPx

The incidence of various types of cancers is increasing every year. Among these, leukemia is extremely common, and thus, developing novel drugs to combat leukemia is crucial. In this study, we designed and synthesized several hybrids and obtained a new lead molecule 5a, with a strong therapeutic effect on leukemia. The results indicated that most hybrids effectively inhibited the growth of leukemia cells, HCT-116, and A549 cancer cells with an IC50 of <10 μM. Among these hybrids, 5a and 4h showed significant anticancer activity against CCRF-CEM, with IC50 values of 0.895 μM and 0.555 μM, respectively. Particularly, 5a had lower toxicity to L02 than chlorambucil (CLB) and doxorubicin (Dox), and the high selectivity was also reflected in the normal human B lymphoblast cell line (IM9). Upon investigating the mechanism of action, we found that 5a downregulated Bcl-2 and caused DNA double-stranded breaks (DSBs) to induce several genotoxic stress responses. The results of the flow cytometry assay showed that 5a was a non-specific molecule in the cell cycle. Furthermore, 5a did not affect total ROS levels but significantly improved the activity of glutathione peroxidase (GPx). Preliminary studies showed that nitrogen mustard exerted an efficient effect, and 5a can combine the advantages of artemisinin and nitrogen mustard and exhibit effects superior to either. This study showed that 5a should be further investigated as a therapeutic compound against leukemia.

S-Shaped Fused Azacorannulene Dimer: Structural and Redox Properties

S-Shaped Fused Azacorannulene Dimer: Structural and Redox Properties

Structural and spectroscopic studies of Na+ – Quercetin-5′-sulfonic acid polymeric complexes obtained via solvothermal synthesis

New sodium complexes of quercetin-5′-sulfonic acid (HQSA) have been obtained. The aqua complex of the general formula [NaQSA∙(H2O)2]·2H2O (1) was a starting compound for solvothermal syntheses of acetone and dimethylsulfoxide (S) complexes: [NaQSA(S)](S) (2 – acetone) and [NaQSA(S)]∙2(S) (3a and 3b – DMSO). The fourth complex obtained from the reaction of HQSA excess used in the reaction with NaOH is [Na(QSA)2·2H2O][(EtOH)2H] (4). The molecular and crystal structures of 1 – 4 were determined by X-ray crystallography. The sodium cations are coordinated by six or seven oxygen atoms; Na+ coordinating groups are sulfonic, hydroxyl, and carbonyl of the QSA− anion. The bridging role of some functional groups causes the formation of polymeric complexes. The coordination spheres are completed by oxygen atoms from the coordinating water (in 1 and 4), acetone (2) or DMSO molecule (3a and 3b). In each structure non-coordinating interstitial solvate molecules are also present; they are two H2O (1), acetone (2), two DMSO (3a and 3b), and the hydrogen bisethanol cation [EtOH…H+…EtOH] (4). The last of these is a rare type of Zundel type cation. Unstable complexes (2 and 3), that decompose under normal conditions, are formed and they have a structure of intercalation clathrates. The solvating molecules, located between 1D or 2D polymeric complexes, play a unique role as a network bonding agent. Theoretical calculations showed charge separation between Na+ and SO3−. The FTIR and Raman spectra are consistent with the solved crystal structures and, importantly, enable the identification of acetone and DMSO molecules in the powder samples.

Synthesis, spectroscopic characterization, single crystal XRD, Hirshfeld Surface analysis and theoretical studies (DFT) of 4-adamantyl-(2-(substitutedbenzylidene)hydrazinyl)thiazoles

In present work, two novel adamantyl based thiazoles were synthesized via simple cyclization reaction of 1-(substitutedbenzylidene)thiosemicarbazides (2) and 1-adamantyl bromomethyl ketone. The structures of resulting compounds 3a and 3b were established with the help of spectro-analytical techniques like; FTIR, 1H-, 13C-NMR and mass spectrometry. The final confirmation of the structures was done with single crystal XRD. All spectroscopic properties of the compounds were further investigated with Density Functional Theory (DFT). The quantum chemical calculations were performed through B3LYP method with 6-311G(d,p), ccPVTZ and ccPVDZ as basis sets to determine bond lengths, bond angles, dihedral angles, frontier molecular orbitals (FMOs) and molecular electrostatic potential (MEP), which revealed that the molecule 3b is strong electrophile while molecule 3a is moderate one. We have also compared the theoretical molecular vibrations and chemical shifts of the compounds with experimental data and results were in good agreement with each other. On the basis of respective correlation co-efficient (σ2) of calculation methods (6-311G(d,p), ccPVTZ and ccPVDZ) it is revealed that ccPVTZ basis sets gave the best results. The MEP analysis revealed that electronegative elements in structure possess the maximum electronic cloud.

π-Pimer, π-Dimer, π-Trimer, and 1D π-Stacks in a Series of Benzene Triimide Radical Anions: Substituent-Modulated π Interactions and Physical Properties in Crystalline State

π-Pimer, π-Dimer, π-Trimer, and 1D π-Stacks in a Series of Benzene Triimide Radical Anions: Substituent-Modulated π Interactions and Physical Properties in Crystalline State

Highly sensitive fluorescence response of [2.2]paracyclophane modified D−A type chromophores to trace water, pH, acidic gases and formaldehyde

Donor (D)−acceptor (A) type compounds have drawn significant attraction recently due to their large Stokes shifted emission and easy-tunable emissive behaviour. Herein, a new family of D−A type [2.2]paracyclophanyl 4H-pyran-4-one fluorescent molecules (3a−3d) have been rationally designed and easily synthesized, and they exhibited intensity and wavelength-based fluorescence sensing in response to active hydrogen, polarity, viscosity and acidic/basic vapours. Therefore, visual and quantitative detection of trace water in different organic solvents with low detection limits of 1.39–8.75 ppm were achieved for 3c; Fluorescence ratiometric detection of pH in the range of 2–7 was achieved for 3b. Moreover, 3a−3d could be served as coated test strips for detecting acidic gases (HCl, TFA, HCOOH and SO2) and HCHO with high sensitivity, reversibility, reproducibility and long-time stability. The response times to TFA vapour were 3–5 s, to HCOOH vapour were 5–7 s and to HCHO vapour 32–70 s. These processes could be readily visualized by unaided eye detection under day light and UV-irradiation. Furthermore, the sensing mechanisms were elucidated by X-ray diffraction, NMR and TD-DFT calculations. The present results suggest that the coated test strips of 3a−3d have potential applications in data encryption and decryption and anti-counterfeiting fields.

Facile Synthesis of Functionalized Phenoxy Quinolines: Antibacterial Activities against ESBL Producing Escherichia coli and MRSA, Docking Studies, and Structural Features Determination through Computational Approach.

The synthesis of new 6-Bromoquinolin-4-ol derivatives (3a–3h) by Chan–Lam coupling utilizing different types of solvents (protic, aprotic, and mixed solvents) and bases was studied in the present manuscript. Furthermore, their potential against ESBL producing Escherichia coli (ESBL E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) were investigated. Commercially available 6-bromoquinolin-4-ol (3a) was reacted with different types of aryl boronic acids along with Cu(OAc)2 via Chan–Lam coupling methodology utilizing the protic and aprotic and mixed solvents. The molecules (3a–3h) exhibited very good yields with methanol, moderate yields with DMF, and low yields with ethanol solvents, while the mixed solvent CH3OH/H2O (8:1) gave more excellent results as compared to the other solvents. The in vitro antiseptic values against ESBL E. coli and MRSA were calculated at five different deliberations (10, 20, 30, 40, 50 mg/well) by agar well diffusion method. The molecule 3e depicted highest antibacterial activity while compounds 3b and 3d showed low antibacterial activity. Additionally, MIC and MBC standards were calculated against the established bacteria by broth dilution method. Furthermore, a molecular docking investigation of the derivatives (3a–3h) were performed. Compound (3e) was highly active and depicted the least binding energy of −5.4. Moreover, to investigate the essential structural and physical properties, the density functional theory (DFT) findings of the synthesized molecules were accomplished by using the basic set PBE0-D3BJ/def2-TZVP/SMD water level of the theory. The synthesized compounds showed an energy gap from 4.93 to 5.07 eV.

Proapoptotic Effect and Molecular Docking Analysis of Curcumin-Resveratrol Hybrids in Colorectal Cancer Chemoprevention.

Different hybrids based on curcumin and resveratrol were previously synthesized and characterized by spectroscopic techniques. The most active molecules (3a, 3e, 3i, and 3k) were evaluated in vitro as an approach to determine the possible mechanism of action of the hybrids. The results indicated that the evaluated curcumin/resveratrol hybrids induce mitochondrial instability in SW620 and SW480 cells. Moreover, these molecules caused a loss in membrane integrity, suggesting an apoptotic process mediated by caspases after the treatment with compounds 3i (SW480) and 3k (SW620). In addition, the results suggest that the mechanism of action of the hybrids could be independent of the p53 status. Furthermore, hybrids 3e and 3i caused G0/G1 phase arrest, which highlights the potential of these molecules not only as cytotoxic but also as cytostatic compounds. Hybrids 3e and 3i caused a negative modulation of the matrix metalloproteinase 7 (MMP7) on SW480 cells. These curcumin resveratrol hybrids could be potential candidates for further investigations in the search for potential chemopreventive agents, even in those cases with resistance to conventional chemotherapy because of the lack of p53 expression or function. Molecular docking simulations showed that compounds 3e, 3i, and 3k bind efficiently to proapoptotic human caspases 3/7 proteins, as well as human MMP-7 and p53, which, in turn, could explain at the molecular level the in vitro cytotoxic effect of these compounds in SW480 and SW620 colon cancer cell lines.

Design, synthesis, and biological evaluation of 3-chloro-2-oxo-N-(arylcarbamoyl)-2H-1-benzopyran-6-sulfonamide derivatives as potential DPP-IV inhibitors

In present work, we aimed at preparing coumarin and sulfonamide containing moieties into a single candidate template i.e. 3-chloro-2-oxo-N-(arylcarbamoyl)-2H-1-benzopyran-6-sulfonamides for the purpose of synergistic activity as potent DPP-IV inhibitors. The designed derivatives were subjected for the calculations of Lipinski rule, Veber’s rule, ADME analysis, drug-likeness properties and molecular docking. The derivatives which successfully passed all the criteria were proceeded for wet lab synthesis and biological evaluation. From the initial screening through Lipinski rule, Veber’s rule, ADME calculations, and drug-likeness properties, molecules 1a, 1f, 1g, 1h, 1i, 1j, 1k, 1o, 1p, 1q, 1r, 1v, 1w, and 1x successfully passed all the filters and displayed most drug-likeness nature. Therefore only these molecules were subjected for molecular docking studies. From molecular docking results, we have selected 1f, 1g, 1i, 1j, and 1v for the wet lab synthesis and biological evaluation. The structures of all the synthesized compounds were confirmed by spectral analysis and were subjected for in vitro DPP-IV enzyme assay. Sitagliptin was used as standard for the assay and it displayed 0.018 µM IC50 value. Compound 1f, 1g, 1i, 1j, and 1v exhibited 15.55, 15.85, 13.95, 14.48, and 13.45 µM IC50 values respectively.

Synthesis, antimicrobial evaluation and molecular modeling studies of novel thiosemicarbazides/semicarbazides derived from p-aminobenzoic acid

The development of novel antimicrobial agents is critical to combat life-threatening drug-resistant bacterial and fungal pathogens. In the present study, a new series of p-aminobenzoic acid (PABA) derivatives carrying thiosemicarbazide/semicarbazide moiety were designed, synthesized, and studied for their antimicrobial activity. The target molecules (3a–f, 4a–f) were achieved by the reaction of 4-aminobenzohydrazide, obtained from PABA, and various phenyl isothiocyanates/isocyanates. Following structural characterization by spectroscopic methods (1H NMR, 13C NMR, FT-IR, and LC-MS analyses), the synthesized compounds were tested for their antimicrobial activity against Staphylococcus aureus, Escherichia coli, Candida albicans, and their clinical isolates. Thiosemicarbazides with lipophilic substituents on the phenyl ring were identified as the most active compounds in this series. Among the studied molecules, compound 3e, thiosemicarbazide derivative with trifluoromethyl groups on the phenyl moiety, showed the best antimicrobial activity. Physicochemical parameters of the compounds were computed to predict the drug-likeness of the title compounds. Finally, molecular docking studies were performed in the allosteric binding pocket of ᴅ-alanine:ᴅ-alanine ligase (Ddl) to explain the potential antibacterial activity mechanism of 3e against S. aureus strains.

Pyrene-based asymmetric hexaarylbenzene derivatives: Synthesis, crystal structures, and photophysical properties

Hexaarylbenzenes (HAB) and their derivatives have attracted considerable attention due to their fantastic molecular geometry and various applications in materials science. Herein, a set of novel, pyrene-based, asymmetric hexaarylbenzene molecules 3a–c and 10 were synthesized and fully characterized by using 1H/13C NMR, single crystal X-ray diffraction, high-resolution mass spectra (HRMS), UV–Vis and fluorescence spectroscopy, as well as density functional theory (DFT) calculations. The compounds show tunable-emission color from violet (366 nm) to deep blue emission (407 nm) following the order of 10 < 3a < 3b < 3c in solution, and the pyrene-based asymmetric hexaarylbenzenes show a red-shift to the (deep) blue region (in the range from 406 to 466 nm) with a narrow full width at half-maximum (FWHM) emission spectrum in films. On the other hand, as the expanding π-conjugated molecular frameworks decreased in the order of 3c > 3b > 3a > 10 > hexaphenylbenzene (HPB), the asymmetric hexaarylbenzenes exhibited clearer aggregation-induced emission characterestics. In addition, DFT calculations indicated that there is strong electronic communication between the pyrene unit and the neighboring phenyl rings by a through-space charge-transfer process, which would play a curial role in lowering the quantum yield in the molecular aggregation state. Thus, this article provides an efficient synthetic strategy on how to design and synthesise high-performance pyrene-based hexaarylbenzene derivatives with narrow FWHM bands for potential applications in organic electronics.

Synthesis, Identification, Computer-Aided Docking Studies, and ADMET Prediction of Novel Benzimidazo-1,2,3-triazole Based Molecules as Potential Antimicrobial Agents.

2-azido-1H-benzo[d]imidazole derivatives 1a,b were reacted with a β-ketoester such as acetylacetone in the presence of sodium ethoxide to obtain the desired molecules 2a,b. The latter acted as a key molecule for the synthesis of new carbazone derivatives 4a,b that were submitted to react with 2-oxo-N-phenyl-2-(phenylamino)acetohydrazonoyl chloride to obtain the target thiadiazole derivatives 6a,b. The structures of the newly synthesized compounds were inferred from correct spectral and microanalytical data. Moreover, the newly prepared compounds were subjected to molecular docking studies with DNA gyrase B and exhibited binding energy that extended from −9.8 to −6.4 kcal/mol, which confirmed their excellent potency. The compounds 6a,b were found to be with the minimum binding energy (−9.7 and −9.8 kcal/mol) as compared to the standard drug ciprofloxacin (−7.4 kcal/mol) against the target enzyme DNA gyrase B. In addition, the newly synthesized compounds were also examined and screened for their in vitro antimicrobial activity against pathogenic microorganisms Staphylococcus aureus, E. coli, Pseudomonas aeruginosa, Aspergillus niger, and Candida albicans. Among the newly synthesized molecules, significant antimicrobial activity against all the tested microorganisms was obtained for the compounds 6a,b. The in silico and in vitro findings showed that compounds 6a,b were the most active against bacterial strains, and could serve as potential antimicrobial agents.

Antitumor Necrosis Factor-like Ligand 1A Therapy Targets Tissue Inflammation and Fibrosis Pathways and Reduces Gut Pathobionts in Ulcerative Colitis.

BackgroundThe first-in-class treatment PF-06480605 targets the tumor necrosis factor-like ligand 1A (TL1A) molecule in humans. Results from the phase 2a TUSCANY trial highlighted the safety and efficacy of PF-06480605 in ulcerative colitis. Preclinical and in vitro models have identified a role for TL1A in both innate and adaptive immune responses, but the mechanisms underlying the efficacy of anti-TL1A treatment in inflammatory bowel disease (IBD) are not known.MethodsHere, we provide analysis of tissue transcriptomic, peripheral blood proteomic, and fecal metagenomic data from the recently completed phase 2a TUSCANY trial and demonstrate endoscopic improvement post-treatment with PF-06480605 in participants with ulcerative colitis.ResultsOur results revealed robust TL1A target engagement in colonic tissue and a distinct colonic transcriptional response reflecting a reduction in inflammatory T helper 17 cell, macrophage, and fibrosis pathways in patients with endoscopic improvement. Proteomic analysis of peripheral blood revealed a corresponding decrease in inflammatory T-cell cytokines. Finally, microbiome analysis showed significant changes in IBD-associated pathobionts, Streptococcus salivarius, S. parasanguinis, and Haemophilus parainfluenzae post-therapy.ConclusionsThe ability of PF-06480605 to engage and inhibit colonic TL1A, targeting inflammatory T cell and fibrosis pathways, provides the first-in-human mechanistic data to guide anti-TL1A therapy for the treatment of IBD.

Design, Synthesis and Anticancer Evaluation of Substituted Cinnamic Acid Bearing 2-Quinolone Hybrid Derivatives.

A new series of hybrid molecules containing cinnamic acid and 2-quinolinone derivatives were designed and synthesized. Their structures were confirmed by 1H-NMR, 13C-NMR and mass analyses. All the synthesized hybrid molecules were assessed for their in vitro antiproliferative activity against more than one cancer cell lines. Compound 3-(3,5-dibromo-7,8-dihydroxy-4-methyl-2-oxoquinolin-1(2H)-ylamino)-3-phenylacrylic acid (5a) with IC50 = 1.89 μM against HCT-116 was proved to the most potent compound in this study, as compared to standard drug staurosporin. DNA flow cytometry assay of compound 5a revealed G2/M phase arrest and pre-G1 apoptosis. Annexin V-FITC showed that the percentage of early and late apoptosis was increased. The results of topoisomerase enzyme inhibition activity showed that the hybrid molecule 5a displays potent inhibitory activity compared with control.

Insights into structural, solvent effect, molecular properties and NLO behavior of hemithioindigo-photoisomerization : A DFT study

The influence of the strength of the electron donor groups on the quantum chemical properties of the Z and E isomerization of some hemithiondigo molecules was investigated via density functional theory (DFT). Electronic, spectroscopic, and thermodynamic properties were studied using DFT and TD-DFT. It was found that 3a is the most reactive molecule compared to 3b and 3c. Moreover, the Z isomer of 3a exhibited small excitation energy, large absorption bands, charge transfer, chemical reactivity, and a higher reaction rate. Molecule 3a also displayed a high electrostatic potential. The most significant NLO response was obtained for Z isomers of 3a (191.80 × 10−30 esu), mainly due to the strong electron-donor group (Diphenylaminyl (-N(Ph)2) present at the para-position of the stilbene part. Based on all the obtained results, it can be concluded that the Z isomer of 3a is a promising HTI switch.

Potential antibacterial ethanol-bridged purine azole hybrids as dual-targeting inhibitors of MRSA

A new class of antibacterial ethanol-bridged purine azole hybrids as potential dual-targeting inhibitors was developed. Bioactivity evaluation showed that some of the target compounds had prominent antibacterial activity against the tested bacteria, notably, metronidazole hybrid 3a displayed significant inhibitory activity against MRSA (MIC = 6 μM), and had no obvious toxicity on normal mammalian cells (RAW 264.7). In addition, compound 3a also did not induce drug resistance of MRSA obviously, even after fifteen passages. Molecular modeling studies showed that the highly active molecule 3a could insert into the base pairs of topoisomerase IA-DNA as well as topoisomerase IV-DNA through hydrogen bonding. Furthermore, a preliminary study on the antibacterial mechanism revealed that the active molecule 3a could rupture the bacterial membrane of MRSA and insert into MRSA DNA to block its replication, thus possibly exhibiting strong antibacterial activity. These results strongly indicated that the highly active hybrid 3a could be used as a potential dual-targeting inhibitor of MRSA for further development of valuable antimicrobials.

Synthesis, biological evaluation and molecular docking studies of heterocycle encompassed benzoxazole derivatives as antimicrobial agents

Novel heterocycles containing benzoxazole nucleus have been synthesized from ethoxy cyano acrylate. All the synthesized molecules were subjected to structural elucidation using spectrometric and spectroscopic characterization using analytical proton NMR (1H), carbon NMR (13C), Fourier transform Infrared spectroscopy (FT-IR) and Liquid chromatography Mass spectrometry. In silico docking studies were carried out to investigate the structural insights into the binding mode to evaluate antimicrobial potency. The docking results against the X-ray crystallographic structure of Staphylococcus aureus UDP-N-acetylenolpyruvylglucosamine reductase (MurB) (PDB ID: 1HSK) protein have shown minimum binding energy of −6.1, −7.6, −7.1, −7.8, and −8.2 for 1A, 2A, 3A, 4A, and 4B molecules respectively. Among which, 4A and 4B molecules have evolved as potential antimicrobial agents from initial screening of the molecules against fungi, gram-positive, and gram-negative bacteria using the agar well diffusion method and minimum inhibition concentration technique.

Theoretical study by DFT of organometallic complexes based on metallocenes active in NLO.

This study is based on the valuation of a few model molecules. The objective of this research is focused on linear optical (LO) and nonlinear optical (NLO) enhancement of five organometallic molecules based on different metallocenes. These molecules were subjected to several calculations by different long-range functionals CAM-B3LYP, LC-BLYP, LC-wPBE, wB97X, M11, and the following three Minnesota functionals: M06-2X and M08-HX in comparison with the MP2 approach. Hence, the CAM-B3LYP functional gave the closest NLO values to the MP2 method. Second, molecule 3A based on nickelocene recorded the highest static (βtot) value which is 76.46 Χ 10-30esu and 4803.4 Χ 10-30esu under the laser wavelength λ = 532nm. Third, intramolecular charge transfers (ICTs) of the molecules studied are all directed in both directions (donor to acceptor and vice versa). Finally, the specific solvent for molecules 2A and 3A is acetonitrile, and the maximum wavelengths obtained for the isolated or solvated molecule are all located in the near UV; the corresponding interval is between 250 and 395nm. Graphical abstract.

Stabilization of Near Identical Hydrogen Bonded Octameric Water Clusters in Crystal Structures of Three Distinct Non-Charged Polyamide Macrocyclic Host Molecules.

In this paper, we present a comparative analysis of the solid state structures of three well-resolved hydrates of macrocyclic host molecules 1a, 1b, and 2 containing an intrannular amide-aryl substituent (lariat arm) connected to a fixed 26-membered ring in a normal (-NHCOAr, hosts 1a and 1b) or reverse manner (-CONHAr, host 2). Despite different chemical structures, these hosts crystallize as isostructural tetrahydrates in the same P-1 space group. Moreover, their crystals exhibit identical hydrogen bond motifs resulting in a stabilization of an almost identical unusual octameric water cluster built from the cyclic tetramer core and four water molecules, attached sequentially in an “up-and-down” manner. Further analysis reveals that, among the series, the structure of host 2 provides the most suitable environment for the accommodation of this type of water cluster.