Conjugated β-Cyclodextrin Enhances the Affinity of Folic Acid towards FRα: Molecular Dynamics Study

Drug targeting is a progressive area of research with folate receptor alpha (FRα) receiving significant attention as a biological marker in cancer drug delivery. The binding affinity of folic acid (FA) to the FRα active site provides a basis for recognition of FRα. In this study, FA was conjugated to beta-cyclodextrin (βCD) and subjected to in silico analysis (molecular docking and molecular dynamics (MD) simulation (100 ns)) to investigate the affinity and stability for the conjugated system compared to unconjugated and apo systems (ligand free). Docking studies revealed that the conjugated FA bound into the active site of FRα with a docking score (free binding energy < −15 kcal/mol), with a similar binding pose to that of unconjugated FA. Subsequent analyses from molecular dynamics (MD) simulations, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) demonstrated that FA and FA–βCDs created more dynamically stable systems with FRα than the apo-FRα system. All systems reached equilibrium with stable RMSD values ranging from 1.9–2.4 Å and the average residual fluctuation values of the FRα backbone atoms for all residues (except for terminal residues ARG8, THR9, THR214, and LEU215) were less than 2.1 Å with a consistent Rg value of around 16.8 Å throughout the MD simulation time (0–100 ns). The conjugation with βCD improved the stability and decreased the mobility of all the residues (except residues 149–151) compared to FA–FRα and apo-FRα systems. Further analysis of H-bonds, binding free energy (MM-PBSA), and per residue decomposition energy revealed that besides APS81, residues HIS20, TRP102, HIS135, TRP138, TRP140, and TRP171 were shown to have more favourable energy contributions in the holo systems than in the apo-FRα system, and these residues might have a direct role in increasing the stability of holo systems.     

Syntheses and Crystal Structures of Four Cobalt Supramolecular Architectures with Hmtyaa Ligand

Four cobalt supramolecular architectures with Hmtyaa(2-(5-methyl-1,3,4-thiadiazol-2-ylthio)acetic acid) ligand have been synthesized.[Co(mtyaa)2(H2O)4]·4(H2O)(1):triclinic,space group P1 with a = 6.7537(18),b = 8.591(2),c = 10.615(3) ,α = 96.495(4),β = 99.955(5),γ = 103.615(5)°,V = 581.9(3) 3,Z = 1,Mr = 581.52,Dc = 1.659 g/m3,μ = 1.158 mm-1,F(000) = 301,Rint = 0.0557,R = 0.0377 and wR = 0.1056 for 1854 observed reflections with Ⅰ 2σ(Ⅰ);{[Co(4,4'-bipy)(H2O)4]·2(mtyaa)·2(H2O)}n(2):triclinic,space group P1 with a = 7.669(2),b = 8.840(3),c = 11.521(4) ,α = 79.912(5),β = 73.954(5),γ = 86.612(6)°,V = 738.9(4) 3,Z = 1,Mr = 701.67,Dc = 1.577 g/m3,μ = 0.924 mm-1,F(000) = 363,Rint = 0.0636,R = 0.0498 and wR = 0.1311 for 2155 observed reflections with Ⅰ 2σ(Ⅰ);{[Co(4,4'-bipy)(mtyaa)(H2O)3](mtyaa)·2(H2O)}(3):monoclinic,space group Pc with a = 7.7832(17),b = 11.527(3),c = 31.483(7) ,β = 91.952(4)°,V = 2822.9(11) 3,Z = 4,Mr = 683.65,Dc = 1.609 g/m3,μ = 0.963 mm-1,F(000) = 1412,Rint = 0.0758,R = 0.0609 and wR = 0.1095 for 5841 observed reflections with I 2σ(I);{[Co(bpe)(mtyaa)2(H2O)2]}n(4):monoclinic,space group C2/c with a = 19.290(11),b = 12.027(7),c = 14.865(8) ,β = 125.648(8)°,V = 2802(3)3,Z = 4,Mr = 657.66,Dc = 1.559 g/m3,μ = 0.959 mm-1,F(000) = 1356,Rint = 0.0456,R = 0.0332 and wR = 0.0985 for 2299 observed reflections with Ⅰ 2σ(Ⅰ).     

Does the G·G*syn DNA mismatch containing canonical and rare tautomers of the guanine tautomerise through the DPT? A QM/QTAIM microstructural study

We have established that the asynchronous concerted double proton transfer (DPT), moving with a time gap and without stable intermediates, is the underlying mechanism for the tautomerisation of the G·G^*_syn DNA base mispair (C₁ symmetry), formed by the keto and enol tautomers of the guanine in the anti- and syn-configurations, into the G^*·G^*_syn base mispair (C₁), formed by the enol and imino tautomers of the G base, using quantum-mechanical calculations and Bader's quantum theory of atoms in molecules. By constructing the sweeps of the geometric, electron-topological, energetic, polar and natural bond orbital properties along the intrinsic reaction coordinate of the G·G^*_syn?G^*·G^*_syn DPT tautomerisation, the nine key points, that are critical for the atomistic understanding of the tautomerisation reaction, were set and comprehensively analysed. It was found that the G·G^*_syn mismatch possesses pairing scheme with the formation of the O6···HO6 (7.01) and N1H···N7 (6.77) H-bonds, whereas the G^*·G^*_syn mismatch – of the O6H···O6 (10.68) and N1···HN7 (9.59 kcal mol^?1) H-bonds. Our results highlight that these H-bonds are significantly cooperative and mutually reinforce each other in both mismatches. The deformation energy necessary to apply for the G·G^*_syn base mispair to acquire the Watson–Crick sizes has been calculated. We have shown that the thermodynamically stable G^*·G^*_syn base mispair is dynamically unstable structure with a lifetime of 4.1 × 10^?15 s and any of its six low-lying intermolecular vibrations can develop during this period of time. These data exclude the possibility to change the tautomeric status of the bases under the dissociation of the G·G^*_syn mispair into the monomers during DNA replication. Finally, it has been made an attempt to draw from the physico-chemical properties of all four incorrect purine–purine DNA base pairs a general conclusion, which claims the role of the transversions in spontaneous point mutagenesis.     

Versatility of cyclodextrins in self-assembly systems of amphiphiles

Recently, cyclodextrins (CDs) were found to play important yet complicated (or even apparently opposite sometimes) roles in self-assembly systems of amphiphiles or surfactants. Herein, we try to review and clarify the versatility of CDs in surfactant assembly systems by 1) classifying the roles played by CDs into two groups (modulator and building unit) and four subgroups (destructive and constructive modulators, amphiphilic and unamphiphilic building units), 2) comparing these subgroups, and 3) analyzing mechanisms. As a modulator, although CDs by themselves do not participate into the final surfactant aggregates, they can greatly affect the aggregates in two ways. In most cases CDs will destroy the aggregates by depleting surfactant molecules from the aggregates (destructive), or in certain cases CDs can promote the aggregates to grow by selectively removing the less-aggregatable surfactant molecules from the aggregates (constructive). As an amphiphilic building unit, CDs can be chemically (by chemical bonds) or physically (by host–guest interaction) attached to a hydrophobic moiety, and the resultant compounds act as classic amphiphiles. As an unamphiphilic building unit, CD/surfactant complexes or even CDs on their own can assemble into aggregates in an unconventional, unamphiphilic manner driven by CD–CD H-bonds. Moreover, special emphasis is put on two recently appeared aspects: the constructive modulator and unamphiphilic building unit.     

Cooperative Effect of CH···O Bonds in Models for Biological Systems

In order to calculate CH···O interactions appearing in biologically important systems, a preliminary study is performed for smaller models. MO bond indices I_XHY are calculated for dimers involving HCN, acetic acid, acetamide, glyoxal and formamide, as well as a ribose33-U35 pair appearing in tRNA^Phe and 3MU-U, also related to RNA. The distance dependence obeys the same pattern for I_OHO, I_NHO and I_CHO. It is shown that the negative I_XHY sign is related to the lengthening of the XH distance; the fluctuation of net charges for the involved atoms is related to the bond index. All results point at a definite cooperative effect.     

IR-Spectroscopic investigation of the hydration of tetrabutylammonium bromide in methylene chloride

The concentration dependence of the H₂O spectra in solutions of tetrabutylammonium bromide Bu₄NBr in methylene chloride was investigated by IR-spectroscopy. At low salt and H₂O concentrations the equilibrium: Br _f ^– +HOH_fBr^–HOH dominates where f indicates free or not hydrogen-bonded Br^– and H₂O. With increasing salt content, Br^–H–O–HBr^– complexes are present in addition. At high salt and H₂O content, including the saturated aqueous Bu₄NBr solution, H-bonded cyclic dimers seem to be important.Presented at the sixth Italian meeting on Calorimetry and Thermal Analysis (AICAT) held in Naples. December 4–7, 1984.     

Progress in (Thio)urea- and Squaramide-Based Brønsted Base Catalysts with Multiple H-Bond Donors

Thiourea- and squaramide-based bifunctional base catalysts represent nowadays a powerful tool in the field of asymmetric catalysis and have demonstrated very efficient for promoting a wide variety of transformations enantioselectively. New versions that incorporate one or various additional H-bond donor site(s) in the catalyst structure have been developed recently which led to more active (reduced catalyst loadings) and selective catalysts. This review highlights the pioneering ideas and the most recent contributions to the area with the material organized according to the nature of the additional H-bond donor functionality. The advantages, current limitations and perspectives of these new multifunctional catalysts are discussed.     

An X-ray study of a 12-crown-4 host-guest complex. Crystal structure of the 4∶6 complex between 12-crown-4 and aminosulfuric acid

The title compound was prepared by treating a methanolic solution of 12-crown-4 with an aqueous solution of aminosulfuric acid. The crystal for X-ray analysis was obtained by recrystallization from acetone. The compound [(12-crown-4)₄·[NH₃SO₃)₆] (1) is monoclinic, space groupP2₁/a,a=21.900(8),b=15.499(5),c=18.079(5) Å, =67.85(2)°. Refinement led to a final conventionalR value of 0.0788 for 3280 reflections. Supplementary Data relating to this publication have been deposited with British Library as Supplementary Publication No. 82160 (22 pages) and include: the list ofF _obs,F _calc; tables of bond distances, bond angles and selected least square planes, as well as a figure of 12-crown-4 in C₄-conformation.     

Type of bond in products of the interaction between primary amines and the copolymer of divinyl ether and malefic anhydride

The nature of the bond in the products of the interaction between primary amines and the copolymer of divinyl ether and malefic anhydride has been studied by IR and electron spectroscopy. The reaction in acetone proceeds with the formation of H-bonded ionic charge transfer complexes where p--conjugation is possible. It is proposed that the biological activity of macromolecular therapeutic systems based on copolymers of maleic anhydride and drugs containing a primary amino group is due to their ability to reversibly dissociate and the presence of local fragments of p--conjugation stabilizing the negative charge.