John Markopoulos

Interaction of thiamine and its phosphate esters with Pt(II) and Pd(II)

Abstract The reactions of Thiamine·HCl (ThH), Thiamine monophosphate·HCl (TMP) and Thiamine pyrophosphate (TPP) have been studied in aqueous solutions (pH ∼3–4) at room temperature. Two types of complexes have been characterized by elemental analyses, conductivity measurements, ir, 1 H nmr and 13 C nmr spectra: ionic 1:2 sults in which thiamine is present as a cation, and 1:1 complexes in which the organic ligand is directly coordinated to the metal ions. The formulae of the ionic salts that were prepared are [MX 4 ] 2− [Th] + 2 and MThX 3 . The salts can easily be converted into 1:1 products by stirring in water at room temperature, while the TPP analogs require excess of ligand. The 1:1 complexes appear to have a zwitterionic structure and the metal is bound through N′ 1 of the pyrimidine ring of thiamine. These solid and stable complexes of thinmine are the first examples reported having a direct metal-to-nitrogen bond.

A novel simple QSAR model for the prediction of anti-HIV activity using multiple linear regression analysis

SummaryA quantitative–structure activity relationship was obtained by applying Multiple Linear Regression Analysis to a series of 80 1-[2-hydroxyethoxy-methyl]-6-(phenylthio) thymine (HEPT) derivatives with significant anti-HIV activity. For the selection of the best among 37 different descriptors, the Elimination Selection Stepwise Regression Method (ES-SWR) was utilized. The resulting QSAR model (R2CV = 0.8160; SPRESS = 0.5680) proved to be very accurate both in training and predictive stages.

Investigation of substituent effect of 1-(3,3-diphenylpropyl)-piperidinyl phenylacetamides on CCR5 binding affinity using QSAR and virtual screening techniques

SummaryA linear quantitative–structure activity relationship model is developed in this work using Multiple Linear Regression Analysis as applied to a series of 51 1-(3,3-diphenylpropyl)-piperidinyl phenylacetamides derivatives with CCR5 binding affinity. For the selection of the best variables the Elimination Selection-Stepwise Regression Method (ES-SWR) is utilized. The predictive ability of the model is evaluated against a set of 13 compounds. Based on the produced QSAR model and an analysis on the domain of its applicability, the effects of various structural modifications on biological activity are investigated. The study leads to a number of guanidine derivatives with significantly improved predicted activities.

Optimization of biaryl piperidine and 4-amino-2-biarylurea MCH1 receptor antagonists using QSAR modeling, classification techniques and virtual screening

This paper presents the results of an optimization study on biaryl piperidine and 4-amino-2-biarylurea MCH1 receptor antagonists, which was accomplished by using quantitative-structure activity relationships (QSARs), classification and virtual screening techniques. First, a linear QSAR model was developed using Multiple Linear Regression (MLR) Analysis, while the Elimination Selection-Stepwise Regression (ES-SWR) method was adopted for selecting the most suitable input variables. The predictive activity of the model was evaluated using an external validation set and the Y-randomization technique. Based on the selected descriptors, the Support Vector Machines (SVM) classification technique was utilized to classify data into two categories: “actives” or “non-actives”. Several attempts were made to optimize the scaffold of most potent compounds by inducing various structural modifications. Potential derivatives with improved activities were identified, as they were classified “actives” by the SVM classifier. Their activities were estimated using the produced MLR model. A detailed analysis on the model applicability domain defined the compounds, whose estimations can be accepted with confidence.

Synthesis of 3-butanoyl- and 3-benzoyl-4-hydroxy-3-pyrrolin-2-ones and their complexes with metal ions

Abstract The new α-acyl-tetramic acids, 3-butanoyl- and 3-benzoyl-4-hydroxy-3-pyrrolin-2-ones have been synthesized and their complexes with Co(II), Ni(II), Cu(II), Cd(II), and Hg(II) prepared. The magnetic and spectroscopic properties of the Co(II), Ni(II), and Cu(II) halide and thiocyanate complexes of formula MX 2 L (L = tetramic acid ligand) indicate that these contain six-coordinated metals with both bridging anions and tetramic acids. The acids appear to be bonded to the metals through the nitrogen atom and a carbonyl oxygen atom. The i.r. spectra indicate the Cd(II) and Hg(II) complexes to be tetrahedral. A few complexes of formula MX 2 L 2 (M = Co, Cu) have been prepared; these also contain six-coordinated metals.

Transition-metal complexes of hydrazones derived from 1,4-diformyl- and 1,4-diacetylbenzenes

Abstract The new ligands 1,4-diformylbenzene bishydrazone (DFBH) and 1,4-diacetylbenzene bishydrazone (DABH) have been prepared. DFBH forms complexes with transition metal(II) ions of types MX2(DFBH) (M = Co, Ni, Mn, Zn or Cd, X = Cl; M = Co or Ni, X = SCN; M = Ni, X = Br) and MX2(DFBH)2 (M = Co, Ni, Mn, Zn, Cd or Hg, X = Cl; M = Ni or Mn, X = Br). DABH forms complexes of types MX2(DABH)2 (M = Co, Ni or Zn, X = Cl or Br; M = Co or Ni, X = Cl, Br or SCN) and MX2(DABH)3 (M = Co, X = Br or SCN; N = Ni X = Cl or SCN; M = Zn, X = Cl, Br or SCN). Electronic spectra, magnetic moments and IR spectra have been used to deduce probable structures of the complexes. All contain six co-ordinated metals in high-spin configurations except ZnCl2(DFBH) and possibly CdCl2(DFBH) which are tetrahedral. The reactions between cobalt(II) halides and DABH in acetone yield the tetrahedral complexes CoX2 (DABAZ), where DABAZ = the acetone azine of 1,4-diacetylbenzene hydrazone.

Tetramic and tetronic acids as scaffolds in bioinorganic and bioorganic chemistry.

Tetramic and tetronic acids are naturally occurring molecules with a variety of biological activities. In this review article, we present the general strategies for the synthesis of these compounds and we reveal the functionalized groups that are responsible for their properties. We also set out their coordinating modes with up-to-date bibliographical references.

Interactions of dichloro-bis(η5-cyclopentadienyl)titanium(IV) with nucleosides

Abstract The interactions of dichloro-bis(η5-cyclopentadienyl)titanium(IV) (titanocene dichloride, Cp2TiCl2) with nucleosides have been studied in methanolic solutions. Complexes of the general formula [Cp2Ti(Nucl)MeOH]Cl2 were isolated. The nucleoside complexes with one N(1)H ionizable imino proton (i.e. inosine and guanosine) undergo ionization in alkaline solution and complexes of the formula [Cp2Ti(NuclH+)] Cl were isolated. All complexes have been characterized by elemental analyses and various spectroscopic techniques. In the first series of complexes, [Cp2Ti(Nucl)MeOH]Cl2, the nucleosides act as monodentate ligands with an intramolecular hydrogen bond between the coordinated methanol and the C6O group, while in the second, [Cp2Ti(NuclH+)] Cl, they coordinate through both their N7 and O6 atoms.

Functionalized 4-Hydroxy Coumarins: Novel Synthesis, Crystal Structure and DFT Calculations

A novel short-step methodology for the synthesis in good yields of functionalized coumarins has been developed starting from an activated precursor, the N-hydroxysuccinimide ester of O-acetylsalicylic acid. The procedure is based on a tandem C-acylation-cyclization process under mild reaction conditions. The structure of 3-methoxycarbonyl-4-hydroxy coumarin has been established by X-ray diffraction analysis and its geometry was compared with optimized parameters by means of DFT calculations.

Rhodium(I) complexes containing the enolate of N-acetyl-3-butanoyltetramic acid (Habta) and the crystal structure of [Rh(abta){P(OPh)3}2]

Reaction of N-acetyl-3-butanoyltetramic acid (Habta)(N-acetyl-3-butanoyl-1,5-dihydro-4-hydroxy-2H-pyrrol-2-one) with [Rh(acac)(CO)2](acac = acetylacetonate) in a 1 : 1 ratio gave [Rh(abta)(CO)2]1 which underwent displacement of CO by either P(OPh)3 or PPh3 to give [Rh(abta)(CO)L][L = P(OPh)3 or 2 PPh34] and [Rh(abta){P(OPh)3}2]3; the reaction of 4 with PPh3 gave the five-co-ordinate complex [Rh(abta)(CO)(PPh3)2]5. The solid-state structure of 3 has been determined by X-ray diffraction. It shows that rhodium adopts a slightly distorted square-planar geometry with the abta enolate ligand adopting an O,O′ mode of co-ordination via the functionalities associated with C4 and the acyl group at C3 in the pyrrolidine ring. Under 13CO, 3 is in equilibrium with 2 and 1 as shown by 13C NMR spectroscopy. No evidence has been found for the formation of five-co-ordinate complexes through the addition of P(OPh)3 to 2.