Synthesis, IR-, NMR-, DFT and X-ray study of ferrocenyl heterocycles from thiosemicarbazones. Part 21: Study on ferrocenes

Cyclization reactions of the thiosemicarbazones of formyl- and acetylferrocene and their S-methyl derivatives with DMAD afforded novel ferrocenyl-hydrazono-substituted thiazolones, one-one dimethylthiazole-4,5-dicarboxylate and 1,3-thiazin-4-one, N-ferrocenylimino-pyrimidones/imidazolones, one intermediate β-adduct and via oxidative cyclization, a ferrocenyl-1,2,4-triazole. Ring isomerization of 1,3-thiazin-4-ones to a 1,3-thiazolones was detected. The structure of the new compounds was established by IR and NMR spectroscopy, including HMQC, HMBC and DEPT measurements and supported with GIAO NMR calculations and controlled also synthetically by phase-transfer methylation. For three compounds the stereostructure was also proved by X-ray diffraction.     

Solid-state structural properties of 2,4,6-trimethoxybenzene derivatives, determined directly from powder X-ray diffraction data in conjunction with other techniques

Structural properties of 2,4,6-trimethoxybenzaldehyde, 2,4,6-trimethoxybenzyl alcohol and 2,4,6-trimethoxyacetophenone have been determined directly from powder X-ray diffraction data, using the direct-space Genetic Algorithm (GA) technique for structure solution followed by Rietveld refinement. Structural similarities and contrasts within this family of materials are elucidated. The work illustrates the value of utilizing information from other sources, including spectroscopic data and computational techniques, as a means of augmenting the structural knowledge established from the powder X-ray diffraction data.     

Interaction of Amino Acid Schiff Base Metal Complexes with DNA/BSA Protein and Antibacterial Activity: Spectral Studies,DFT Calculations and Molecular Docking Simulations

Cu(II), Ni(II) and Zn(II) complexes of (E)‐2‐((2,4‐dihydroxybenzylidene)amino)‐3‐(1H‐indol‐3‐yl)propanoic acid Schiff base ( L ) were synthesized and characterized by various spectral methods. ESI‐MS was used to confirm the structure of synthesized compounds. Molecular geometries of the complexes were predicted by optimizing the structure by DFT/B3LYP method with LANL2DZ basis set in the gas phase. The interaction of the metal complexes with CT‐DNA and BSA protein has been examined by UV‐vis, fluorescence and viscometer titrations reveal that the complexes bind to DNA through intercalation binding mode. The copper complexes exhibit effective cleavage of pUC19 DNA by the oxidative mechanism. The synthesized compounds screened for their antibacterial activities against various bacteria strains exhibit the L and copper complex show potential activity against Pseudomonas aeruginosa and Escherichia coli, respectively. Subsequently, molecular docking studies were performed on to understand the binding of the compounds with DNA, BSA and bacteria.     

Perfluorophenyl phosphonate analogues of aromatic amino acids: Synthesis,X-ray and DFT studies

Novel perfluorophenyl phosphonate analogues of phenylglycine and homophenylalanine were prepared in good to excellent yields, and subjected to solid state characterization by single-crystal X-ray diffraction analysis, and to investigations with the use of DFT methods.The α-aminophosphonates have a big potential for biological activity, and through S_NAr reactions may give an entrance to further structurally variable analogues of both amino acids.     

Crystal and molecular structure, hydrogen bond and electrostatic interactions of bis(1-methylisonicotinate)hydrogen perchlorate studied by X-ray diffraction, DFT calculations, FT-IR, Raman and NMR spectroscopes

The crystal structure of bis(1-methylisonicotinate)hydrogen perchlorate, (MIN)₂H·ClO₄, has been studied by X-ray diffraction, DFT calculations, FT-IR, Raman, ¹H and ¹³C NMR spectra. The crystals are monoclinic, space group P2₁/n, with a pair of MIN molecules bridged by a short asymmetrical O·H·O hydrogen bond of 2.461(5) Å. The COO groups are twisted by 80.55° with respect to the plane of the pyridine ring. The anion interacts electrostatically with the positively charged nitrogen atoms of the neighbouring MIN molecules. The most stable conformer of isolated (MIN)₂H·ClO₄ and two homoconjugated cations, (MIN)₂H, have been analyzed by the B3LYP/6-31G(d,p) calculations in order to determine the influence of the anion on the hydrogen bonds in MIN·H·MIN unit. The FT-IR spectrum of the (MIN)₂H·ClO₄ shows a broad and intense absorption in the 1500–400 cm⁻¹ region, typical of short hydrogen bonds. The isotopic ratio, νOHO/νODO, is close to unity, indicating that the hydrogen bond is acentric (pseudo-type A).     

Synthesis, spectroscopic characterization, X-ray structure and DFT studies on 4-(2-hydroxyphenyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-5-ium chloride hydrate

The title molecular salt, 4-(2-hydroxyphenyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-5-ium chloride hydrate (C₁₂H₁₄N₃O⁺·Clˉ·H₂O), was synthesized and characterized by IR-NMR spectroscopy and single-crystal X-ray diffraction. In addition to the molecular geometry from X-ray experiment, the molecular geometry, vibrational frequencies and gauge-independent atomic orbital (GIAO) ¹H and ¹³C NMR chemical shift values of the title compound in the ground state have been calculated using the density functional theory (DFT/B3LYP) method with the 6-31++G(d,p) and 6-311++G(d,p) basis sets, and compared with the experimental data. Besides, molecular electrostatic potential (MEP) distribution and non-linear optical properties of the title compound were investigated by theoretical calculations at the B3LYP/6-311++G(d,p) level.     

A NMR, X-ray, and DFT combined study on the regio-chemistry of nucleophilic addition to platinum(II) coordinated terminal olefins

The series of platinum complexes [PtCl(η²-CH₂CH-C₆H₄-X)(tmeda)](ClO₄) (X = H, 1b; 4-OMe, 1c; 3-OMe, 1d; 4-CF₃, 1e; 3-CF₃, 1f; 3-NO₂, 1g; tmeda = N,N,N′,N′-tetramethyl-1,2-ethanediamine) has been considered. In the styrene complex (1b) both solution (NMR) and solid state (X-ray) data indicate a significant difference in the Pt-C bond lengths (the longer bond being that involving the olefin carbon atom carrying the phenyl ring). Such a difference increases when X is an electron donor group (EDG, 1c) and decreases when X is an electron withdrawing group (EWG, 1d-g). The attack of a nucleophile (MeO⁻) to the substituted carbon (Markovnikov type, M) is by far the most favoured in the case of unsubstituted (1b) or EDG-substituted (1c) styrenes. The presence of an EWG (compounds 1d-g) levels off the probability of M and anti-M type of attack. DFT calculations on 1b,c and 1e were also performed. The NLMO analysis reveals the crucial role of the interaction between the filled π orbital of the olefin and the empty d orbital of platinum; the carbon with greater electron density becoming less susceptible of nucleophilic attack.     

X-ray diffraction, DFT theoretical, and IR polarized spectroscopic studies of the crystal-like E-mesophase of 4′-hexyloxy-isothiocyanatotolane (6OTOLT)

The dynamics of 6OTOLT molecules was analyzed based on IR absorption spectra and DFT calculations. Of particular interest was the mode ascribed to the ν_as(NCS) vibrations, the transition dipole moment of which is directed along the long axes of the molecules. Polarized IR spectra in the region of this mode allowed a characterization of the ordering of molecules in the analyzed phases. In a case of the smectic E phase, a random distribution of molecules aligned laterally in two-dimensional space between KRS-5 windows was found. The crystals of 6OTOLT were successfully grown and are characterized by an interesting Pc space group. The molecules are parallely arranged in layers and cross the adjoining ones underneath at an angle of 86.04°. The distance between the ring planes is 3.48 Å. The packing of molecules indicates a tendency to maintain short contacts between NCS groups and alkyl chains. The crystals grown do not correspond to the ordering of the smectic E phase and thus to the solid state obtained after cooling the smectic phase. Calculations of the interaction energy for three possible arrangements of dimeric species show a predominance of the core-to-core units. It was also shown that in this case an increase in ν_as(NCS) frequency should be expected, in good agreement with experimental data.     

Halogen-Bonded Assemblies of Arylene Imides and Diimides: Insight from Electronic,Structural, and Computational Studies

Halogen-bonding interactions in electron-deficient π scaffolds have largely been underexplored. Herein, the halogen-bonding properties of arylene imide/diimide-based electron-deficient scaffolds were studied. The influence of scaffold size, from small (phthalimide) to moderately sized (pyromellitic diimide or naphthalenediimides) to large (perylenediimide), axial-group modification, and number of halo substituents on the halogen bonding and its self-assembly was probed in a set of nine compounds. The structural modification leads to tunable optical and redox properties. The first reduction potential ranges between −1.09 and −0.17 V (vs. SCE). Two of the compounds, that is, 6 and 9 , have deep-lying LUMOs with values reaching −4.2 eV. Single crystals of all nine systems were obtained, which showed Br ⋅⋅⋅ O, Br ⋅⋅⋅ Br, or Br ⋅⋅⋅ π halogen-bonding interactions, and a few systems are capable of forming all three types. These interactions lead to halogen-bonded rings (up to 12-membered), which propagate to form stacked 1D, 2D, or corrugated sheets. A few outliers were also identified, for example, molecules that prefer C−H ⋅⋅⋅ O hydrogen bonding over halogen bonding, or noncentrosymmetric rather than centrosymmetric organization. Computational studies based on Atoms in Molecules and Natural Bond Orbital analysis provided further insight into the halogen-bonding interactions. This study can lead to a predictive design tool-box to further explore related systems on surfaces reinforced by these weak directional forces.     

Antioxidant,Antimicrobial and Antitumor Studies of Transition Metal Complexes Derived from N-(2-Aminoethyl)-1,3-Propanediamine with DFT Calculations and Molecular Docking Investigation

New expected biologically active complexes for some of the first (Mn (II), Ni (II), Cu (II) and Zn (II)) and second (Rh (III) and Cd (II)) transitional metals rows with N-(2-Aminoethyl)-1,3-propanediamine as a ligand (AEPD)have been synthesized. All synthesized complexes were formed with 1:1 (metal: AEPD) stoichiometry except Ni (II) 1:2 (Ni: AEPD). The compounds were characterized by different analysis tools such as; elemental analysis, Fourier transform infrared (FTIR), ¹H-NMR, mass spectra, thermal analysis, electronic spectra, magnetic measurement and molar conductance techniques. AEPD ligand interacted with all metal ions as tridentate ligand by using the nitrogen atoms. On the other hand, density functional theory (DFT) calculations have been performed to confirm the optimized geometrical structures for both AEPD and its complexes. Furthermore, coordination compounds were screened for their potential antibacterial activities against six pathogenic bacteria as well as one kind of fungi in comparison to standard antibiotics by agar well diffusion method. The results show that most of the complexes exhibit antibacterial and antifungal activities against these organisms. Rh (III)-AEPD complex exhibited the strongest antibacterial effect followed by the Cd (II) complex but as antifungal agents Cd (II) was the first and the second was Rh (III). Also, the anticancer activity was screened for these metal complexes against growth of human liver cancer HEPG2 tumor cell line and this inhibition activity of Cd (II) chelate was noticed to be more active with lowest IC₅₀ than that of all other synthesized complexes. Unfortunately, Mn (II) and Rh (III) chelates lacked anticancer activity. The docking active sites interactions were evaluated using the selected protein for anticancer activity. Finally, antioxidant activity was studied. Mn (AEPD) showed maximum activity followed by complex of Rh (III).     

Novel Bis- and Mono-Pyrrolo[2,3-d]pyrimidine and Purine Derivatives: Synthesis,Computational Analysis and Antiproliferative Evaluation

Novel symmetrical bis-pyrrolo[2,3-d]pyrimidines and bis-purines and their monomers were synthesized and evaluated for their antiproliferative activity in human lung adenocarcinoma (A549), cervical carcinoma (HeLa), ductal pancreatic adenocarcinoma (CFPAC-1) and metastatic colorectal adenocarcinoma (SW620) cells. The use of ultrasound irradiation as alternative energy input in Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) shortened the reaction time, increased the reaction efficiency and led to the formation of exclusively symmetric bis-heterocycles. DFT calculations showed that triazole formation is exceedingly exergonic and confirmed that the presence of Cu(I) ions is required to overcome high kinetic requirements and allow the reaction to proceed. The influence of various linkers and 6-substituted purine and regioisomeric 7-deazapurine on their cytostatic activity was revealed. Among all the evaluated compounds, the 4-chloropyrrolo[2,3-d]pyrimidine monomer 5f with 4,4′-bis(oxymethylene)biphenyl had the most pronounced, although not selective, growth-inhibitory effect on pancreatic adenocarcinoma (CFPAC-1) cells (IC₅₀ = 0.79 µM). Annexin V assay results revealed that its strong growth inhibitory activity against CFPAC-1 cells could be associated with induction of apoptosis and primary necrosis. Further structural optimization of bis-chloropyrrolo[2,3-d]pyrimidine with aromatic linker is required to develop novel efficient and non-toxic agent against pancreatic cancer.     

First Trifluoromethylated Phenanthrolinediamides: Synthesis,Structure, Stereodynamics and Complexation with Ln(III)

The first examples of 1,10-phenanthroline-2,9-diamides bearing CF₃-groups on the side amide substituents were synthesized. Due to stereoisomerism and amide rotation, such complexes have complicated behavior in solutions. Using advanced NMR techniques and X-ray analysis, their structures were completely elucidated. The possibility of the formation of complex compounds with lanthanoids nitrates was shown, and the constants of their stability are quantified. The results obtained are explained in terms of quantum-chemical calculations.     

Structure of the complex of dimethylphenyl betaine with dichloroacetic acid studied by X-ray diffraction,DFT calculations,infrared and Raman spectra

The structure of the complex of dimethylphenyl betaine (DMPB) with dichloroacetic acid (DCA) (1) has been investigated by X-ray diffraction, FTIR and Raman spectroscopy, and B3LYP/6-311 + + G(d,p) calculations. The crystal is monoclinic, space group P2₁. The acid is connected with betaine through the OH⋯O hydrogen bond of 2.480(2) Å. In the optimized structure the short, asymmetric O⋯O distance is 2.491 Å. FTIR spectrum shows a broad absorption in the 1500–400 cm⁻¹ region characteristic of very short OH⋯O hydrogen bond caused by Fermi resonance between νOH and overtones of δOH and γOH. In the Raman spectrum this broad absorption is not observed. The potential energy distributions (PED) were used for the assignments of IR and Raman frequencies in the experimental and calculated spectra. The FTIR and Raman spectra of the crystal complex are consistent with the X-ray results.     

Stemmosides C and D, two novel unusual pregnane glycosides from Solenostemma argel: structural elucidation and configurational study by a combined NMR-quantum mechanical strategy

Stemmosides C and D, two novel pregnane glycosides characterized by an unusual C-17 side chain were isolated from the pericarps of Solenostemma argel. In addition, stemmoside D displays an uncommon 14β proton configuration, apparently being the first pregnane isolated from plants known to have a 15 keto, cis CD ring junction. Their structures have been established by ESIMS and NMR experiments. The relative configuration of the molecules was determined using a strategy based on the simulation of ¹H, ¹³C, and J coupling NMR parameters. DFT calculations of ¹H and ¹³C chemical shifts, and of the ¹H homonuclear spin–spin coupling constants were performed with the mPW1PW91 functional using the 6-31G(d,p) basis set on the fully optimized geometries of all the possible stereoisomers.     

X-ray structure,spectroscopic characterisation and DFT calculations of the [Re(CO)3(2,2′-biquinoline)Cl] complex

The fac-[Re(CO)₃(2,2′-biquinoline)Cl] complex has been obtained in reaction of Re(CO)₅Cl with 2,2′-biquinoline. The compound has been studied by IR, UV–Vis spectroscopy and X-ray crystallography. The molecular orbital diagram of the tricarbonyl has been calculated with the density functional theory (DFT) method. The spin-allowed singlet–singlet electronic transitions of [Re(CO)₃(2,2′-biquinoline)Cl] have been calculated with the time-dependent DFT method, and the UV–Vis spectrum of the title compound has been discussed on this basis.     

Dihydrogen Generation from Amine/Boranes: Synthesis,FT‐ICR,and Computational Studies

A Fourier transform ion cyclotron resonance spectrometry (FT‐ICR) study of the gas‐phase protonation of ammonia‐borane and sixteen amine/boranes R¹R²R³N? BH₃ (including six compounds synthesized for the first time) has shown that, without exception, the protonation of amine/boranes leads to the formation of dihydrogen. The structural effects on the experimental energetic thresholds of this reaction were determined experimentally. The most likely intermediate and the observed final species (besides H₂) are R¹R²R³N? BH₄⁺ and R¹R²R³N? BH₂⁺, respectively. Isotopic substitution allowed the reaction mechanism to be ascertained. Computational analyses ([MP2/6‐311+G(d,p)] level) of the thermodynamic stabilities of the R¹R²R³N? BH₃ adducts, the acidities of the proton sources required for dihydrogen formation, and the structural effects on these processes were performed. It was further found that the family of R¹R²R³N? BH₄⁺ ions is characterized by a three‐center, two‐electron bond between B and a loosely bound H₂ molecule. Unexpected features of some R¹R²R³N? BH₄⁺ ions were found. This information allowed the properties of amine/boranes most suitable for dihydrogen generation and storage to be determined.     

Homodecoupled 1,1‐ and 1,n‐ADEQUATE: Pivotal NMR Experiments for the Structure Revision of Cryptospirolepine

Cryptospirolepine is the most structurally complex alkaloid discovered and characterized thus far from any Cryptolepis specie. Characterization of several degradants of the original, sealed NMR sample a decade after the initial report called the validity of the originally proposed structure in question. We now report the development of improved, homodecoupled variants of the 1,1‐ and 1,n‐ADEQUATE (HD‐ADEQUATE) NMR experiments; utilization of these techniques was critical to successfully resolving long‐standing structural questions associated with crytospirolepine.     

New oxorhenium complexes with the 8-quinolinolato ligand: X-ray structure and DFT calculations for [ReOBr(hqn)2]

The reactions of [ReO(OEt)X₂(PPh₃)₂] (X = Cl or Br) with 8-hydroxyquinoline (Hhqn) have been examined and the [ReOX(hqn)₂] complexes have been obtained. The crystal and molecular structures of [ReOBr(hqn)₂] have been determined. The electronic structure of [ReOBr(hqn)₂] has been calculated with the density functional theory (DFT) method, and additional information about binding in the ReO³⁺ unit has been obtained by NBO analysis. The spin-allowed electronic transitions of [ReOBr(hqn)₂] have been calculated with the time-dependent DFT method, and the UV–Vis spectra of the [ReOX(hqn)₂] compounds have been discussed on this basis.