Detailed potential of mean force studies on host–guest systems from the SAMPL6 challenge

Accurately predicting receptor–ligand binding free energies is one of the holy grails of computational chemistry with many applications in chemistry and biology. Many successes have been reported, but issues relating to sampling and force field accuracy remain significant issues affecting our ability to reliably calculate binding free energies. In order to explore these issues in more detail we have examined a series of small host–guest complexes from the SAMPL6 blind challenge, namely octa-acids (OAs)–guest complexes and Curcurbit[8]uril (CB8)–guest complexes. Specifically, potential of mean force studies using umbrella sampling combined with the weighted histogram method were carried out on both systems with both known and unknown binding affinities. We find that using standard force fields and straightforward simulation protocols we are able to obtain satisfactory results, but that simply scaling our results allows us to significantly improve our predictive ability for the unknown test sets: the overall RMSD of the binding free energy versus experiment is reduced from 5.59 to 2.36 kcal/mol; for the CB8 test system, the RMSD goes from 8.04 to 3.51 kcal/mol, while for the OAs test system, the RSMD goes from 2.89 to 0.95 kcal/mol. The scaling approach was inspired by studies on structurally related known benchmark sets: by simply scaling, the RMSD was reduced from 6.23 to 1.19 kcal/mol and from 2.96 to 0.62 kcal/mol for the CB8 benchmark system and the OA benchmark system, respectively. We find this scaling procedure to correct absolute binding affinities to be highly effective especially when working across a “congeneric” series with similar charge states. It is less successful when applied to mixed ligands with varied charges and chemical characteristics, but improvement is still realized in the present case. This approach suggests that there are large systematic errors in absolute binding free energy calculations that can be straightforwardly accounted for using a scaling procedure. Random errors are still an issue, but near chemical accuracy can be obtained using the present strategy in select cases.     

Synthesis and host–guest complexation,photophysical and electrochemical studies on novel thiophenophanes

Synthesis of thiophene-based cyclophanes called thiophenophanes is described. The photophysical and electrochemical properties of thiophenophanes synthesised reveal that they show permanent fluorescence-sensing property, and the cyclic voltammogram reflects the ease with which the electron on the sulphur atom can be removed. Complexation studies of the thiophenophanes with TCNQ reveal the formation of 1:1 complex.     

Electrochemistry and electrochemiluminescence for the host–guest system laponite–tris(2,2′-bipyridyl)ruthenium(II)

The cationic luminescence probe, tris(2,2′-bipyridyl)ruthenium(II) complex ([Ru(bpy)₃]²⁺), was incorporated into laponite-modified glassy carbon electrode (GCE) via two strategies, namely, the adsorption and intercalation methods. These two incorporation methods resulted in different microenvironment for the immobilized [Ru(bpy)₃]²⁺ within laponite as well as the different host–guest and guest–guest interactions. Herein, cyclic voltammetry and electrochemiluminescence (ECL) were innovatively performed to monitor the interactions. Tripropylamine (TPA) was used as coreactant in the electrochemical and ECL system.     

Infrared Spectroscopic and Gravimetric Studies on the Dicyclopentylaminemetal(II) Tetracyanonickellate(II) Host–Aromatic Guest Systems

The host complexes M(Cyclopentylamine)₂Ni(CN)₄ (M=Co or Cd) havebeen prepared in powder form. The spectral data suggest that the structures of thesecompounds are similar to those of the Hofmann-dma-type hosts. The absorptionand the liberation processes of the aromatic guests (benzene, toluene, 1,2-, 1,3-,1,4-dichlorobenzene, 1,4-dibromobenzene o-, m-, p-xylene, naphthalene)in these hosts have been examined at room temperature by gravimetric and spectroscopicmeasurements. The desorption of the benzene guest against time has been measured. Thehost structures do not change on inclusion and liberation of the guests. The host compoundshave been suggested as sorbents for isomeric separations.     

Self-assembled (pseudo)rotaxane and polyrotaxane through host–guest chemistry based on the cucurbituril family

Cucurbit[n]uril and its derivatives, a new family of macrocyclic hosts comprising n glycoluril units, have gained much attention for their exceptional application in many fields. In this review, we introduced the cucurbituril family and the development of its derivatives, which can be used in the molecular recognition and self-assembled materials such as pseudorotaxane, polyrotaxane. Moreover, cucurbituril provides the possibility to design stimulus–response devices and imitate the life secret at molecule level, such as the molecular devices controlled by pH, photochemistry, thermal and so on.     

Host–guest interactions between dapsone and β-cyclodextrin (Part II): thermal analysis, spectroscopic characterization, and solubility studies

The complex of dapsone with β-cyclodextrin was prepared by the co-precipitation/freeze–drying method. The physical–chemical characteristics of the complex were investigated by different methods and compared with those of the physical mixture and of the isolated compounds. The methods used were infrared spectroscopy, X-ray diffractometry and differential scanning calorimetry. The stability constant was calculated from phase solubility diagram (Higuchi–Connors) and fluorescence spectroscopy. The stoichiometry of the complex was confirmed by Job’s plot. Fluorescence measurements at different temperatures provided the thermodynamic parameters of the complexation. The infrared spectrum showed the disappearance of the SO₂ asymmetric stretching band of the drug at 1275?cm^?1 after complexation. The amorphization of the samples, as revealed by the X-ray diffraction patterns, was an indirect proof of the inclusion complex. The thermal analysis showed that the curves of the physical mixture are combination of the curves of both constituents (dapsone and β-cyclodextrin) while the absence of the melting peak of the drug in the DSC curve of the complex suggests the inclusion of the drug molecule in the host cavity as a 1:1 complex as indicated by Job’s plot. There was a linear increase in its solubility with the increase of the cyclodextrin concentration and the complex was classified as an A_L-type. The value of the stability constant was 3,998?L?mol^?1 calculated by the Higuchi–Connors diagram and around 18,100?L?mol^?1 from the fluorescence method indicating a strong interaction between the host and the guest. Complex formation was a spontaneous and enthalpy directed process.     

Solid-state NMR studies of host–guest chemistry in metal-organic frameworks

Metal-organic frameworks (MOFs) are an emerging class of porous materials with potential applications in a wide variety of fields. The knowledge about the detailed interactions between MOFs and guest molecules is critical for the understanding of their structure-property relationships at working conditions. In this review, recent advances for solid-state NMR studies of host–guest chemistry of MOFs in the application fields of gaseous adsorption, chemical separation, drug delivery, chemical sensor, and heterogeneous catalysis were briefly introduced. The adsorption property and dynamic behavior of adsorbed gases confined inside the MOFs channels were elucidated from variable-temperature (VT) solid-state NMR. Moreover, the detailed mechanism of gas-phase and liquid-phase adsorptive separations on MOFs adsorbents was uncovered on the basis of solid-state NMR measurements. Multi-nuclear ¹H, ¹³C, ¹⁵N, and ³¹P MAS NMR was utilized to explore the interactions between drug molecules and MOFs at the atomic scale to monitor the controlled release process of drugs. Furthermore, the investigation of the interactions between guest molecules and MOFs in the application areas of chemical sensor, toxic chemicals removal, and catalysis using solid-state NMR was briefly discussed as well.     

Physicochemical characterization and molecular modeling study of host–guest systems of aripiprazole and functionalized cyclodextrins

Journal of Thermal Analysis and Calorimetry - Aripiprazole (ARP), an innovative atypical antipsychotic drug, exhibits very low aqueous solubility, affecting its dissolution and absorption and high...     

Transition metal atoms grafted on the nanodiamonds surface: Identification and guest–host spin–spin interactions

This survey describes recent achievements in creating a new type of materials – nanodiamonds grafted with atoms of transition metals. Structural features of some selected chelate complexes studied by density functional theory, their scope and limitations as well as possible applications are discussed. Using the example of copper ions, their location relative to subsurface defects of detonation diamond is investigated by the method of electron paramagnetic resonance (EPR).     

Infrared spectroscopic and DFT investigations of the vanadate–tellurate glasses structures

Vanadate–tellurate vitreous systems with composition (1 ? x)TeO₂·xV₂O₅ where x = 0.3 and 0.4 have been prepared by the conventional melt-quench method. The structural aspects have been investigated using FTIR spectroscopy and the density functional theory (DFT) calculations.The present study provides the interesting information concerning devitrification behavior of the vanadate–tellurate vitreous system which occur Te₂V₂O₉ crystalline phase. The structure of the heat-treated glasses was found to consist mainly of rings containing [TeO₃], [TeO₄], [VO₄] and some [VO₅] structural units.     

A hybrid hydrogel based on clay nanoplatelets and host–guest inclusion complexes

In this work,a monomer with double bond was introduced to the surface of clay nanosheets via inclusion complexation between cyclodextrin(CD)host and azobenzene(Azo)guest,as well as electrostatic interaction between clay nanoplatelets and cations of azobenzene derivatives.The obtained suprastructure acts as a supramolecular cross-linker in its copolymerization with macromonomer PEG resulting in a hybrid supramolecular hydrogel.Only viscous liquid was obtained in the absence of clay nanoplatelets,revealing the supramolecular cross-linker played an important role in the hydrogel formation.Such hybrid supramolecular hydrogel exhibited good stability and shear thinning property.     

Thermodynamic studies on the systems M–Te–O (M = Nd,Sm)

The standard Gibbs energies of formation of Nd₂TeO₆ and M₆TeO₁₂ (where M = Nd, Sm) were determined from vapour pressure measurements. The vapour pressure of TeO₂(g) was measured by employing thermogravimetry-based transpiration technique. The temperature dependence of the vapour pressure of TeO₂(g) over the mixtures Nd₂TeO₆+Nd₆TeO₁₂, generated by the incongruent vapourisation reaction, 3Nd₂TeO₆(s) → Nd₆TeO₁₂(s)+2TeO₂(g)+O₂(g), was measured in the temperature range 1,408–1,495 K. Similarly, the vapour pressure of TeO₂(g) over the mixtures M₆TeO₁₂+M₂O₃ (where M = Nd, Sm), generated by the incongruent vapourisation reaction, M₆TeO₁₂(s) → 3M₂O₃(s)+TeO₂(g)+½O₂(g), was measured in the temperature range 1,703–1,773 and 1,633–1,753 K for Nd₆TeO₁₂(s) and Sm₆TeO₁₂(s), respectively. Enthalpy increments of M₂TeO₆(s) (where M = Nd, Sm) were determined by inverse drop calorimetric method in the temperature range 573–1,273 K. The thermodynamic functions, viz., heat capacity, entropy and free energy functions, were derived from the measured values of enthalpy increments. A mean value of ?2,426.2 ± 0.6 and ?2,417.9 ± 1.1 kJ mol^?1 was obtained for $ \Updelta_{\text{f} } H_{298}^{\text{o}} $ (Nd₂TeO₆, s) and $ \Updelta_{\text{f}} H_{298}^{\text{o}} $ (Sm₂TeO₆, s), respectively, by combining the value of $ \Updelta_{\text{f}} G^{\text{o}} $ (Nd₂TeO₆, s) and $ \Updelta_{\text{f}} G^{\text{o}} $ (Sm₂TeO₆, s) derived from vapour pressure data and the free energy functions derived from the drop calorimetric data.     

Theoretical studies on the spectroscopic properties and the substituent effects of pyridyl triazole Os(Ⅱ) complexes

To explore the spectroscopic properties of pyridyl triazole Os(Ⅱ) complexes and how the substituent effects affect the spectroscopic properties of [Os(ptz)2L2] (L=PH3; ptzH=(2-pyridyl)-1,2,4-triazole) (1), [Os(bptz)2L2] (bptzH=3-tert-butyl-5-(2-pyridyl)-1,2,4-triazole) (2), [Os(fptz)2L2] (fptzH=3- (trifluoreomethyl)- 5-(2-pyridyl)-1,2,4-triazole) (3), and [Os(fbtz)2L2] (fbtzH=3-(trifluoreomethyl)-5-(4-tert-butyl- 2-pyridyl)-1,2, 4-triazole) (4), the density functional theory (DFT) method at the B3LYP level ...     

DNA-binding and photocleavage studies of metallofluorescein–porphyrin complexes of zinc(II) and copper(II)

The DNA-binding behaviors of the fluorescein?Cporphyrinatozinc(II) complex Zn(Fl-PPTPP) (Fl-PPTPP?=?5-(4-fluoresceinpropyloxy)phenyl-10,15,20-triphenylporphyrin) and fluorescein?Cporphyrinatocopper(II) complex Cu(Fl-PPTPP) with calf thymus DNA (CT-DNA) were investigated by UV?CVis absorption titrations, fluorescence spectra, viscosity measurements, thermal denaturation and circular dichroism. The results suggest that both complexes interact with CT-DNA by intercalation. In addition, their photocleavage reactions with pBR322 supercoiled plasmid DNA were investigated. Both complexes exhibit significant DNA cleavage activity, and singlet oxygen may play an important role in these reactions.     

Absolute binding free energy calculations of CBClip host–guest systems in the SAMPL5 blind challenge

Herein, we report the absolute binding free energy calculations of CBClip complexes in the SAMPL5 blind challenge. Initial conformations of CBClip complexes were obtained using docking and molecular dynamics simulations. Free energy calculations were performed using thermodynamic integration (TI) with soft-core potentials and Bennett’s acceptance ratio (BAR) method based on a serial insertion scheme. We compared the results obtained with TI simulations with soft-core potentials and Hamiltonian replica exchange simulations with the serial insertion method combined with the BAR method. The results show that the difference between the two methods can be mainly attributed to the van der Waals free energies, suggesting that either the simulations used for TI or the simulations used for BAR, or both are not fully converged and the two sets of simulations may have sampled difference phase space regions. The penalty scores of force field parameters of the 10 guest molecules provided by CHARMM Generalized Force Field can be an indicator of the accuracy of binding free energy calculations. Among our submissions, the combination of docking and TI performed best, which yielded the root mean square deviation of 2.94 kcal/mol and an average unsigned error of 3.41 kcal/mol for the ten guest molecules. These values were best overall among all participants. However, our submissions had little correlation with experiments.     

The effect of heavy metals on the anthracene–Me-β-cyclodextrin host–guest inclusion complexes

Anthracene was used to form an inclusion complex with methylated-β-cyclodextrin (Me-β-CD) in water. In aqueous Me-β-CD solution, typical fluorescence emission of anthracene was observed. Benesi–Hildebrand's method was used to obtain the stoichiometry of the anthracene–Me-β-CD complex. The Stern–Volmer quenching constants, K_sv, and fluorescence quantum yields were calculated according to changes in the fluorescence emission intensity of anthracene–Me-β-CD inclusion complexes by adding various amounts of Pb²⁺ and Cd²⁺ salts in water. The K_sv values and fluorescence quantum yields indicate that Pb²⁺ salts quench the anthracene–Me-β-CD inclusion complexes more efficiently than Cd²⁺ salts.     

Theoretical studies on electronic structures and spectroscopic properties of a series of novel β-diketonate Os(II) complexes

The geometries, electronic structures, and spectroscopic properties of a series of [Os^(II)(CO)₃(tfa)(acac(X)₂)] (tfa = trifluoroacetate; acac = acetoylacetonate; X = H (1), CF₃ (2), C₆H₅ (3), and C₁₀H₇ (4)) complexes have been investigated theoretically. The ground and excited state geometries were optimized at the B3LYP/LANL2DZ and CIS/LANL2DZ levels, respectively. The optimized geometry structural parameters agreed well with the corresponding experimental results. As indicated in this paper, the highest occupied molecular orbitals were dominantly localized on the Os atom, ctfa (abbv. of CO and tfa), and acac ligand for 1 and 2, acac ligand and X substituent for 3 and 4, while the lowest unoccupied molecular orbitals were mainly composed of acac ligand and X substituent. Under the time-dependent density functional theory (TDDFT) level with the polarized continuum model (PCM), the absorption and phosphorescence in CH₂Cl₂ media were calculated based on the optimized ground- and excited-state geometries, respectively. The calculated results show that the lowest energy absorptions at 317 (1), 342 (2), 377 (3), and 420 nm (4) are attributed to a change of ππ*/MLCT mixing transition to pure ππ* transition for 1–4, while their phosphorescence emission have similar transition properties. This indicates that the absorption and emission transition characters could be altered by adjusting the π electron-donating ability.     

Synthesis,crystal structure,thermal decomposition,and XPS studies of homo and heterotrinuclear Cu(II)–Cu(II)–Cu(II) and Cu(II)–Ni(II)–Cu(II) complexes obtained from salpn type ligands

In this study, a mononuclear CuL complex was prepared by the use of bis-N,N′-(salicylidene)-1, 3-propanediamine (LH₂) and Cu²⁺ ion. NiCl₂ and NiBr₂ salt were treated with this complex in dioxanewater medium and two new complexes [(CuL)₂NiCl₂(H₂O)₂] and [(CuL)₂NiBr₂(H₂O)₂)] with Cu(II)–Ni(II)–Cu(II) nucleus structure were obtained. In addition to this bis-N,N′-(2-hydroxybenzyl)-1,3-diaminopropane (L^HH₂) was prepared by the reduction of LH₂ with NaBH₄ in MeOH medium. The treatment of this reduced complex with Cu²⁺ ion resulted a complex [(CuL^H)₂CuCl₂] with a structure of Cu(II)–Cu(II)–Cu(II). The complexes prepared were characterized by the use of elemental analysis, IR spectroscopy, thermogravimetric and X-ray diffraction methods. The crystal structures of [(CuL)₂NiBr₂(H₂O)₂] (СIF file CCDC 1448402) and [(CuL^H)₂CuCl₂] (СIF file CCDC 1448401) complexes were elucidated. It was found that halogen ions are coordinated to terminal Cu²⁺ ions which are in a distorted square pyramid coordination sphere. It was determined that the central Cu(II), which joins terminal square pyramidal Cu(II), was coordinated only by the phenolic oxygens of the ligand while the central Ni(II) was coordinated by two phenolic oxygens of the organic ligand and two water molecules. These complexes were investigated by XPS and it was found that the terminal and central Cu²⁺ ions were different in Cu(II)–Cu(II)–Cu(II) complex. Also, the thermal degradation of the CuLH complex unit was observed to exothermic in contrast to the expectations.

     

Infrared spectroscopic studies of hydrogen bonded complexes of water with oxygen bases—II. Aliphatic and alicyclic ethers

The i.r. spectra, in the OH-stretching region, of solutions of water at very low concentrations in a number of aliphatic and alicyclic ethers have been recorded. The band envelopes have been resolved into a number of component peaks, and assignments proposed for these components in terms of the hydrogen bonded complexes formed. The wavenumbers, half-widths and intensities of the component bands, and the total hydrogen bonded OH-stretching intensities, have been determined and used as indicators of the relative strengths of the solute—solvent hydrogen bonds. These spectroscopic properties have also been correlated with some of the physical properties of the solvents.     

Molecular modeling and spectroscopic studies on the binding of guaiacol to human immunoglobulin

The fluorogenic property of guaiacol was exploited for the first time to analyze the interaction with target protein as a probe by molecular modeling, fluorescence, circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopy. Molecular docking was performed to reveal the possible binding mode or mechanism and suggested that guaiacol can strongly bind to human immu- noglobulin (HIgG). It is considered that guaiacol binds to HIgG mainly by a hydrophobic interaction and there are two hydrogen bond interactions between the drug and the residues LEU 80 and ASP 65, which is in good agreement with the results from the experimental thermodynamic parameters (the enthalpy change △H0 and the entropy change △S0 were calculated to be 65.55 kJ·mol-1 and 132.95 J·mol-1·K-1 according to the Vant’ Hoff equation). Data obtained by the fluorescence spectroscopy indicated that binding of guaiacol with HIgG leads to dramatic enhancement in the fluorescence emission intensity along with significant occurrence of efficient Frster resonance energy transfer (FRET) from the residue of HIgG to the protein bound guaiacol. From the low value of fluorescence anisotropy (r = 0.06), it is argued that the probe molecule is located in the motionally unrestricted environment of the protein. The alterations of protein’s secondary structure in the presence of guaiacol in aqueous solution were quantitatively calculated by the evidences from FT-IR and CD spectroscopes.