Pr Complexes Research Articles

Homodinuclear lanthanide complexes of phenylthiopropionic acid: Synthesis, characterization, cytotoxicity, DNA cleavage, and antimicrobial activity

Lanthanide complexes of La(III), Pr(III), Nd(III), Sm(III), and Ho(III) with phenylthiopropionic acid were synthesized and characterized by elemental analysis, mass, IR, electronic spectra, molar conductance, TGA, and powder XRD. The results show that the lanthanide complexes are homodinuclear in nature. The two lanthanide ions are bridged by eight oxygen atoms from four carboxylate groups. Thermal decomposition profiles are consistent with the proposed formulations. Powder XRD studies show that all the complexes are amorphous in nature. Antimicrobial studies indicate that these complexes exhibit more activity than the ligand itself. The DNA cleavage activity of the ligand and its complexes were assayed on Escherichia coli DNA using gel electrophoresis in the presence of H2O2. The result shows that the Pr(III) and Nd(III) complexes have completely cleaved the DNA. The anticancer activities of the complexes have also been studied towards human cervical cancer cell line (HeLa) and colon cancer cells (HCT116) and it was found that the La(III) and Nd(III) complexes are more active than the corresponding Pr(III), Sm(III), Ho(III) complexes, and the free ligand on both the cancer cells.

INVESTIGATION OF SOME PHYSICOCHEMICAL PROPERTIES OF 4-NITROCINNAMATES OF LANTHANIDES(III)

ABSTRACT Lanthanide(III) 4-nitrocinnamates were synthesized as polycrystalline hydrated solids with the general formulae: Ln(C 9 H 6 NO 4 ) 3 ·nH 2 O (where Ln = lanthanons (without Ce(III)), n=1 for La, Pr-Tb and n=2 for Dy-Lu). The complexes were characterized by elemental analysis, FTIR spectroscopy, magnetic and thermogravimetric studies and also by X-ray diffraction (XRD) measurements. The carboxylate groups bind as bidentate chelating. On heating to 1173 K in air all compounds at first dehydrate in one stage to form anhydrous salts, that next with rising temperature are being directly decomposed (complexes of Pr(III) and Eu(III)) or with the intermediate formation of oxycarbonates (the rest of analysed compounds) to the oxides of respective metals. The gaseous products of compound thermal decomposition in nitrogen were also determined. The magnetic susceptibilities were measured over the ranges 76-303 K and 1.8-303 K, and their magnetic moments were calculated. The results show that 4-nitrocinnamates of lanthanides(III) are high-spin complexes with weak ligand field.

Lanthanoid metal nitrates with hydrogen bonded hexamethylenetetramine

Cerium, praseodymium, and neodymium nitrate complexes with hydrogen bonded hexamethylenetetramine (HMTA) of the formula [Ce(NO3)2(H2O)5](HMTA)2(NO3)(H2O)3, [Pr(NO3)2(H2O)6]2[Pr(H2O)9](HMTA)6(NO3)6(H2O)4 and [Nd(NO3)2(H2O)5](HMTA)2(NO3)(H2O)3 have been prepared and characterized by X-ray crystallography. All the complexes belong to monoclinic crystal system. Ce and Nd complexes have P21/n space group, whereas Pr complex has C2/c. Thermal analyses of these complexes were carried out using TG, DSC, which showed their multi-step decomposition. Kinetics of thermolysis has been done by applying model fitting as well as model free isoconversional method. In order to see the response of rapid heating, ignition delay measurements were carried out. The thermal decomposition pathways have also been demonstrated. On the basis of thermal studies the thermal stability of the complexes was found in the order; Pr > Ce > Nd. In order to identify the end products of thermolyses, X-ray diffraction patterns of end product were carried out which showed the formation of corresponding metal oxides.

Novel PCU cage diol peptides as potential targets against wild-type CSA HIV-1 protease: synthesis, biological screening and molecular modelling studies

We have synthesized a series of novel pentacycloundecane cage diol diacid (PCU diol diacid) incorporated C2-symmetric peptides. Their activity against the resistance-prone wild-type C-South African (C-SA) HIV protease (HIV PR) is reported. These compounds were obtained in moderate yields of 42–72 %. Amongst the nine compounds reported herein only compound 6, 7, 10 and 11 showed moderate IC50 values of 5–10 μM. Peptides 7 and 10 contain two phenylglycine and two tryptophan amino acids, respectively as side arms to the cage diol. Phenylglycine is a non-natural amino acid. Docking and molecular dynamics (MD) studies were carried out to understand the binding mode of the PCU moiety at the active site of the HIV PR enzyme. The computational results show that the cage diol peptide fits quite comfortably inside the active site of the enzyme. Not much movement is observed during the MD simulation and the hydrogen bonds that develop between the inhibitor and the enzyme pocket suggest that the inhibitor/HIV PR complex is stable at room temperature.

Energy migration toward a dye in nanoparticles from complexes with short fluorescent state lifetimes

We have studied regular features of the fluorescence sensitization (cofluorescence) of coumarin 30 and rhodamine 6G introduced into nanoparticles from complexes Ln(PhBTA) 3 phen, where PhBTA is pphe� nylbenzoyltrifluoroacetone and Ln is a triply charged Pr, Nd, Sm, Eu, Er, or Yb ion, which absorbs in the fluorescence range of ligands of complexes and dyes. We show that both the cofluorescence intensities (Icofl) of rhodamine 6G in nanoparticles from Sm and Eu complexes and the behavior of intensity Icofl on the con� tent of rhodamine 6G coincide with the corresponding data obtained for nanoparticles from La and Lu com� plexes doped with rhodamine 6G molecules. A considerable decrease in I cofl of rhodamine 6G is observed only in nanoparticles from complexes Nd(PhBTA)3phen. In nanoparticles from Pr, Nd, Sm, Eu, Er, and Yb complexes doped with coumarin 30, it has been observed that, depending on the choice of the central ion, Icofl of coumarin 30 is 2 to 80 times lower compared to Icofl of the dye in nanoparticles from La and Lu com� plexes. A separate analysis of the influence of these ions on the energy transfer from complexes to coumarin 30 and on the fluorescence intensity of coumarin 30 incorporated into nanoparticles from these ions showed that a decrease in Icofl of coumarin 30 by a factor of 2-20 occurs due to the reduction of τfl of ligands of com� plexes under the influence of the interaction with Pr, Nd, Sm, Eu, Er, and Yb ions. Since τfl of complexes La(PhBTA)3phen is ~2 ps, while that of complexes Gd(PhBTA)3phen is ~1 ps, then, in nanoparticles with a maximal decrease in I cofl of coumarin 30, τ fl of complexes is reduced to ~0.1 ps. It has been found that, in nanoparticles from complexes with this τ fl , energy migration over complexes takes place. However, as distinct from nanoparticles from La, Lu, and Y complexes, the free path length of singlet excitons in nanoparticles from complexes of absorbing ions is smaller than the nanoparticle size.

Comparison of the Molecular Dynamics and Calculated Binding Free Energies for Nine FDA‐Approved HIV‐1 PR Drugs Against Subtype B and C‐SA HIV PR

We report the first account of a comparative analysis of the binding affinities of nine FDA-approved drugs against subtype B as well as the South African subtype C HIV PR (C-SA). A standardized protocol was used to generate the inhibitor/C-SA PR complexes with the relative positions of the inhibitors taken from the corresponding X-ray structures for subtype B complexes. The dynamics and stability of these complexes were investigated using molecular dynamics calculations. Average relative binding free energies for these inhibitors were calculated from the molecular dynamics simulation using the molecular mechanics generalized Born surface area method. The calculated energies followed a similar trend to the reported experimental binding free energies. Postdynamic hydrogen bonding and electrostatic interaction analysis of the inhibitors with both subtypes reveal similar interactions. Most inhibitors show slightly weaker binding affinities for C-SA PR. Molecular dynamics studies demonstrated increased flap movement for C-SA PR, which can perhaps explain the weaker affinities. This study serves as a standardized platform for optimizing the design of future more potent HIV C-SA PR inhibitors.

Evaluation of intensity and energy interaction parameters for the complexation of Pr(III) with selected nucleoside and nucleotide through absorption spectral studies

The interactions of Pr(III) with nucleosides and nucleotides have been studied in different organic solvents employing absorption difference and comparative absorption spectrophotometry. The magnitudes of the variations in both energy and intensity interaction parameters were used to explore the degree of outer and inner sphere co-ordination, incidence of covalency and the extent of metal 4f-orbital involvement in chemical bonding. Various electronic spectral parameters like Slater–Condon (Fk), Racah (Ek), Lande parameter (ξ4f), Nephelauxatic ratio (β), bonding (b1/2), percentage covalency (δ) and intensity parameters like oscillator strength (P) and Judd Ofelt electronic dipole intensity parameter (Tλ, λ=2,4,6) have been evaluated. The variation of these evaluated parameters were employed to interpret the nature of binding of Pr(III) with different ligands i.e. Adenosine/ATP in presence and absence of Ca2+.

Luminescence Tuning and White‐Light Emission of Co‐doped Ln–Cd–Organic Frameworks

Four new three-dimensional isostructural lanthanide-cadmium metal-organic frameworks (Ln-Cd MOFs), [LnCd(2)(imdc)(2)(Ac)(H(2)O)(2) ]·H(2)O (Ln=Pr (1), Eu (2), Gd (3), and Tb (4); H(3)imdc=4,5-imidazoledicarboxylic acid; Ac=acetate), have been synthesized under hydrothermal conditions and characterized by IR, elemental analyses, inductively coupled plasma (ICP) analysis, and X-ray diffraction. Single-crystal X-ray diffraction shows that two Ln(III) ions are surrounded by four Cd(II) ions to form a heteronuclear building block. The blocks are further linked to form 3D Ln-Cd MOFs by the bridging imdc(3-) ligand. Furthermore, the left- and right-handed helices array alternatively in the lattice. Eu-Cd and Tb-Cd MOFs can emit characteristic red light with the Eu(III) ion and green light with the Tb(III) ion, respectively, while both Gd-Cd and Pr-Cd MOFs generate blue emission when they are excited. Different concentrations of Eu(3+) and Tb(3+) ions were co-doped into Gd-Cd/Pr-Cd MOFs, and tunable luminescence from yellow to white was achieved. White-light emission was obtained successfully by adjusting the excitation wavelength or the co-doping ratio of the co-doped Gd-Cd and Pr-Cd MOFs. These results show that the relative emission intensity of white light for Gd-Cd:Eu(3+),Tb(3+) MOFs is stronger than that of Pr-Cd:Eu(3+),Tb(3+) MOFs, which implies that the Gd complex is a better matrix than the Pr complex to obtain white-light emission materials.

Computational Studies of Darunavir into HIV-1 Protease and DMPC Bilayer: Necessary Conditions for Effective Binding and the Role of the Flaps

Human immunodeficiency virus type 1 protease (HIV-1 PR) is one of the main targets toward AIDS therapy. We have selected the potent drug darunavir and a weak inhibitor (fullerene analog) as HIV-1 PR substrates to compare protease's conformational features upon binding. Molecular dynamics (MD), molecular mechanics Poisson-Boltzmann surface area (MM-PBSA), and quantum-mechanical (QM) calculations indicated the importance of the stability of HIV-1 PR flaps toward effective binding: a weak inhibitor may induce flexibility to the flaps, which convert between closed and semiopen states. A water molecule in the darunavir-HIV-1 PR complex bridged the two flap tips of the protease through hydrogen bonding (HB) interactions in a stable structure, a feature that was not observed for the fullerene-HIV-1 PR complex. Additionally, despite that van der Waals interactions and nonpolar contribution to solvation favored permanent fullerene entrapment into the cavity, these interactions alone were not sufficient for effective binding; enhanced electrostatic interactions as observed in the darunavir-complex were the crucial component of the binding energy. An alternative pathway to the usual way of a ligand to access the cavity was also observed for both compounds. Each ligand entered the binding cavity through an opening between the one flap of the protease and a neighboring loop. This suggested that access to the cavity is not necessarily regulated by flap opening. Darunavir exerts its biological action inside the cell, after crossing the membrane barrier. Thus, we also initiated a study on the interactions between darunavir and the DMPC bilayer to reveal that the drug was accommodated inside the bilayer in conformations that resembled its structure into HIV-1 PR, being stabilized via HBs with the lipids and water molecules.

Studies on the complexation of Pr(III) and Nd(III) with glycyl–glycine (gly–gly) using spectral analysis of 4f–4f transitions and potentiometric titrations

The interaction of gly–gly with Pr(III) and Nd(III) have been studied in different aquated organic solvents like CH3OH, CH3CN, dioxane and DMF by using 4f–4f transitions spectra. Various energy interaction parameters like Slater Condon (Fk), Racah (Ek), Lande (ξ4f), nephelauxetic effect (β), bonding (b1/2) and percent covalency (δ) parameters have been calculated to explain the nature of complexation. The intensity parameters like oscillator strength (P) and Judd–Ofelt parameters (Tλ, λ=2, 4, 6) also support the mode of binding of gly–gly to metal ions. The results show that Pr(III) and Nd(III) with gly–gly form complexes by ionic linkages with carboxylate anion with weak covalency. The protonation constants and metal–ligand stability constants have also been determined by potentiometric measurements in aqueous medium at different temperatures (290, 300 and 310K) at constant ionic strength, 0.1moldm−1. The results show the formation of metal–ligand complexes in the stoichiometric ratio 1:1. The stability of complexes is more in Nd(III) complexes as compared to Pr(III) complexes. Thermodynamic parameters (ΔG, ΔH and ΔS) of complexes were also calculated and the negative values of ΔG and ΔH show that the complex reactions are spontaneous and exothermic. The positive values of ΔS indicate high stability of complex reactions which are enthalpy-driven.

Complexation of N'-[1-(3-aminophenyl)ethylidine]isonicotinohydrazide with La3+, Pr3+, Nd3+, Sm3+, Eu3+ and Gd3+ ions and associated thermodynamics

A novel Schiff base N'-[1-(3-aminophenyl)ethylidine]isonicotinohydrazide was prepared and its complexation behavior towards some selected lanthanides had been studied employing pH-metric and calorimetric titration and spectral techniques. pH-metric studies were carried out for the trivalent La, Pr, Nd, Sm, Eu, and Gd complexes in 30% aqueous-dioxane medium at constant ionic strength of 0.05 mol/L NaClO4 and at different temperatures of 293, 303 and 313 K. The proton-ligand formation constants of the ligand indicated the presence of only one dissociable proton while the metal-ligand formation constants were compatible with the formation of 1:1 Ln(III) complexes. The stability of the complexes followed the order: La3+<Pr3+<Nd3+<Sm3+<Eu3+>Gd3+, showing a break at gadolinium. The thermodynamic parameters, ΔG, ΔH and ΔS associated with protonation and complexation reactions were negative which suggested that all reactions were exothermic and enthalpy-driven. Isothermal calorimetric studies of Gd3+-aeINH systems at 303 K also showed exothermic nature of the complexation reaction and formation of 1:1 complex in agreement with the pH-metric data. Formation of 1:1 complexes was confirmed by the characterization of Nd(III) complex. A seven coordinated geometry was assigned for the complex based on its elemental and spectral data.

Synthesis and Spectral Characterization of Praseodymium(III) Complex with New Amino Acid-Based Azo Dye

A new Praseodymium (Pr) (III) complex has been synthesized and characterized by using a new amino acid-based (leucine) azo dye such as N,N-dimethylazoleucine (L1) and 1,10 phenanthroline (L2). Reaction of Pr(III) ion with L1 and L2 in 1 : 2 : 1 ratio in alcoholic medium has been carried out with general formula [Pr(L1)2(L2)(H2O)2]. Elemental analysis, comparative FT-IR, and 1HNMR spectral studies of Pr(III) complex with ligands have been shown in this paper.

A low-cost sensitizer based on a phenolic resin for charge-transfer type photocatalysts working under visible light

Phenolic resin (denoted as PR) was used as an economical sensitizer of titania to achieve efficient visible light photocatalytic activity. Through the surface complexation of PR with TiO(2), we demonstrate that the complexed PR layer sensitizes TiO(2) under visible light through the ligand-to-metal charge transfer (LMCT) mechanism.

Thermal and spectroscopic studies of sodium and light lanthanide (III) complexes with 2,4-pyridinedicarboxylate anion

Pyridine-2,4-dicarboxylic acid (lutidinic acid) is next one after pyridine-2,5-dicarboxylic acid of the six isomers which lanthanide complexes were studied thermally and spectrally. New complexes synthesized with light lanthanides (III) with general formula Ln2L3·nH2O, where n = 7.5; 8; 8.5; 9, were obtained. Sodium salt was obtained as hexahydrated compound. Hydrated complexes of La(III), Ce(III), Pr(III), Nd(III), Sm(III), Eu(III), and Gd(III) are thermally stable up to 303–313 K. Dehydration process run for all compounds in one stage, anhydrous compounds decompose through appropriate light lanthanides (III) oxalates, oxocarbonates, carbonates to metal oxides. Theoretical IR and Raman studies were carried out in order to identify precisely characteristic group bands vibrations present on IR and Raman spectra.

A comparative study of 1H NMR and sensitized visible light emission of an extended series of dinuclear lanthanide complexes

An extended series of dinuclear lanthanide β-diketonate complexes of the type [Ln 2(fod) 6(μ-bpm)] (Ln = Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu; fod is the anion of 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedione; bpm = 2,2′-bipyrimidine) and polymeric complexes of the type [Ln(fod) 3(bpm)] n (Ln = La and Pr) have been isolated and thoroughly investigated in solution, by means of 1H NMR and steady-state luminescence spectroscopies. The 1H NMR chemical shift for the protons of paramagnetic complexes is analysed and discussed. The typical sensitized red, pink, green and yellow emission of Pr(III)/Eu(III), Sm(III), Tb(III) and Dy(III) complexes, respectively, is observed upon the excitation of the coordinated ligands. The comparison of the steady-state luminescence intensities of the complexes reveals that ligand-to-metal energy transfer is most efficient in Eu(III) complex followed by Sm(III) and Pr(III) complexes. The Tb(III) and Dy(III) complexes show relatively weak luminescence due to inefficient energy transfer.

Synthesis, characterization and biological evaluation of a novel series of mixed ligand complexes of lanthanides(III) with 4[N-(furfural)amino]antipyrine semicarbazone as primary ligand and diphenyl sulfoxide as secondary ligand

A novel series of complexes of lanthanides(III) with 4[N-(furfuralamino]antipyrine semicarbazone (FFAAPS) as the primary ligand and diphenyl sulfoxide (DPSO) as the secondary ligand with the general composition LnX3(FFAAPS)nDPSO (X = NO3 -, n = 1; X = NCS- or ClO4 -, n = 2; Ln = La3+, Pr3+, Nd3+, Sm3+, Gd3+, Tb3+, Dy3+ or Ho3+), is reported. All the synthesized complexes were characterized through various physico-chemical techniques i.e. elemental analysis, conductance measurements and magnetic susceptibilities, spectroscopic and thermal studies. The coordinated FFAAPS behaved as tridentate N,N,O-donor, while DPSO acted as unidentate oxygen donor. Nitrates were bicovalently bonded, while the thiocyanate was coordinated through N-atom. Perchlorate ions did not participate in the coordination sphere. The absorption bands of the representative Pr(III), Nd(III) and Sm(III) complexes in the visible and near infrared region appeared due to transitions from the ground levels to the excited J-levels of 4f-configuration. From the hypersensitive bands, the nephelauxetic effect (β) was calculated. And from the β-values, the covalence factor (b1/2), Sinha parameter (δ%) and the covalency angular overlap (η) were calculated. The ligand and the corresponding lanthanide(III) complexes were simultaneously screened for their antibacterial and antifungal activities. Thermal stabilities of these complexes were studied by thermogravimetric analysis. Depending on the nature of the anionic ligands, the coordination number of the lanthanide(III) in the case of nitrate or thiocyanate complexes was ten, while it was seven in the case of perchlorate complexes.

사배위 N2O2Schiff 염기 리간드와 그 희토류 금속착물의 합성 및 특성

o-phenylenediamine, 3-acetyl-6-methyl-(2H)pyran,2,4(3H)-dione (dehydroacetic acid 또는 DHA) 및 2, 4-dihydroxy benzaldehyde에서 비롯된 4-hydroxy-3-(1-{2-(2,4-dihydroxy-benzylidene)-amino phenylimino}-ethyl)-6-methyl-pyran-2-one (<TEX>$H_2$</TEX>L)의 La(III), Ce(III), Pr(III), Nd(III), Sm(III) 및 Gd(III) 고체착물을 합성하여 원소분석, 전도도법, 자기수자율, UV-vis, FT-IR, 1H-NMR, X-선 회절, 열분석으로 특성을 규명하였으며, 항미생물 활성도를 조사하였다. FT-IR 스펙트럼 결과에 의하면 이 리간드는 중심금속에 대해 ONNO 주개원자를 통해 이염기성 사배위 리간드로 행동함을 알 수 있다. 원소분석 결과로부터 이들 착물의 화학량론비는 1:1 (금속: 리간드)임을 알 수 있다. 물리 및 화학적 실험결과로부터 La(III), Ce(III), Pr(III), Nd(III), Sm(III) 및 Gd(III) 착물은 일그러진 팔면체의 기하구조를 가짐을 알 수 있다. X-선 회절 데이터로부터 La(III) 및 Ce(III) 착물은 단사정계, 그리고 Pr(III) 및 Nd(III) 착물은 사방정계를 가짐을 알 수 있다. 이들 착물의 열적 행동(TG/DTA)을 연구하였으며, 속도론적 파라메타를 Horowitz-Metzger 및 Coats-Redfern 방법으로 결정하였다. 리간드와 그 착물의 항박테리아 활성도를 Staphylococcus aureus, Escherichia coli 및 Bacillus Sp.에 대해, 그리고 살균활성도를 Aspergillus Niger, Trichoderma 및 Fusarium oxysporum에 대해 각각 조사하였다. The solid complexes of La(III), Ce(III), Pr(III), Nd(III), Sm(III) and Gd(III) with 4-hydroxy-3-(1-{2-(2,4-dihydroxy-benzylidene)-amino phenylimino}-ethyl)-6-methyl-pyran-2-one (<TEX>$H_2$</TEX>L) derived from o-phenylenediamine, 3-acetyl-6-methyl-(2H)pyran,2,4(3H)-dione (dehydroacetic acid or DHA) and 2, 4-dihydroxy benzaldehyde have been synthesized and characterized by elemental analysis, conductometry, magnetic susceptibility, UV-visible, FT-IR, <TEX>$^1H$</TEX>-NMR, X-ray diffraction, thermal analysis study, and screened for antimicrobial activity. The FT-IR spectral data suggest that the ligand behaves as a dibasic tetradentate ligand with ONNO donor atoms sequence towards central metal ion. From the microanalytical data, the stoichiometry of the complexes has been found to be 1:1 (metal: ligand). The physico-chemical data suggests distorted octahedral geometry for La(III), Ce(III), Pr(III), Nd(III), Sm(III) and Gd(III) complexes. The X-ray diffraction data suggests monoclinic crystal system for La(III) and Ce(III) and orthorombic crystal system for Pr(III) and Nd(III) complexes. Thermal behavior (TG/DTA) of the complexes was studied and kinetic parameters were determined by Horowitz-Metzger and Coats-Redfern methods. The ligand and its metal complexes were screened for antibacterial activity against Staphylococcus aureus, Escherichia coli, Bacillus Sp. and fungicidal activity against Aspergillus Niger, Trichoderma and Fusarium oxysporum.

Absorption spectral analysis of 4f–4f transitions for the complexation of Pr(III) and Nd(III) with thiosemicarbazide in absence and presence of Zn(II) in aqueous and organic solvents

The complexation of thiosemicarbazide with Pr(III) and Nd(III) in absence and presence of Zn(II), a soft metal ion in aqueous and organic solvents like CH 3OH,CH 3CN, dioxane (C 4H 8O 2) and DMF (C 3H 7NO) and their equimolar mixtures are discussed by employing absorption difference and comparative absorption spectrophotometry. Complexation of thiosemicarbazide with Pr(III) and Nd(III) is indicated by the changes in the absorption intensity following the subsequent changes in the oscillator strength of different 4f–4f bands and Judd-Ofelt intensity ( T λ ) parameters. The other spectral parameters like energy interaction parameters namely Slater–Condon ( F k ), Racah ( E k ), Lande ( ξ 4f), Nephelauxetic ratio ( β) and bonding parameters ( b 1/2) are further computed to explain the nature of complexation. The difference in the energy parameters with respect to donor atoms and solvents reveal that the chemical environment around the lanthanide ions has great impact on f–f transition and any change in the environment result in modification of the spectra. Various solvents and their equimolar mixtures are also used to discuss the participation of solvents in the complexation.

Synthesis and structural studies of pentacycloundecane-based HIV-1 PR inhibitors: A hybrid 2D NMR and docking/QM/MM/MD approach

Pentacycloundecane (PCU) lactam-peptide based HIV protease inhibitors were synthesized and nanomolar activity against the resistance-prone wild type C-South African HIV protease is reported. NMR investigations indicated that the activity is related to the chirality of the PCU moiety and its ability to induce conformations of the coupled peptide side chain. EASY-ROESY NMR experiments gave information about the 3D structure of the cage peptides and 3D solution structure could be linked to the experimental IC 50 activity profile of the considered inhibitors. QM/MM/MD simulations of the inhibitors in solution confirmed the NMR observed conformations. Docking experiments and QM/MM/MD simulations of the inhibitor-HIV PR complexes were also performed. These computational results complimented the experimental inhibition activities and enabled us to report a unique binding mode for PCU-based inhibitors at the active site of HIV-protease enzyme. A conserved hydrogen bonding pattern between the norstatine type functional group of the PCU hydroxylactam and active site residues, ASP25/ASP25′, was observed in all active compounds. The biological significance and possible mode of inhibition by PCU-based HIV PR inhibitors discussed herein provide us with a deeper understanding of the mode of action of these novel inhibitors. The PCU-peptides are between 6000 and 8500 time less toxic to human MT-4 cells than Lopinavir. This potentially creates new application avenues for these putative inhibitors to be investigated against a vast number of other disease-related proteases.

Fluorescence and DNA-binding properties of neodymium(III) and praseodymium(III) complexes containing 1,10-phenanthroline

The binding of neodymium(III) and praseodymium(III) complexes containing 1,10-phenanthroline, [M(phen) 2Cl 3·OH 2] (M = Nd ( 1), Pr ( 2)), to DNA has been investigated by absorption, emission, and viscosity measurements. The complexes show absorption decreasing in charge transfer band, fluorescence decrement when bound to DNA. The binding constant K b has been determined by absorption measurement for both complexes and found to be (6.76 ± 0.12) × 10 4 for 1 and (1.83 ± 0.15) × 10 4 M −1, for 2. The fluorescence of [M(phen) 2Cl 3·OH 2] (M = Nd ( 1), Pr ( 2)) has been studied in detail. The results of fluorescence titration reveal that DNA has the strong ability to quenching the intrinsic fluorescence of Nd(III) and Pr(III) complexes through the static quenching procedure. The binding site number n, apparent binding constant K b and the Stern–Volmer constant k SV are determined. Thermodynamic parameters, enthalpy change (Δ H°) and entropy change (Δ S°), are calculated according to relevant fluorescent data and Van’t Hoff equation. The experimental data suggest that the complexes bind to DNA by non-intercalative mode. Major groove binding is the preferred mode of interaction for [M(phen) 2Cl 3·OH 2] (M = Nd ( 1), Pr ( 2)) with DNA.