Nucleophilic Substitution at Heteroatoms—Identity Substitution Reactions at Phosphorus and Sulfur Centers: Do They Proceed in a Concerted (SN2) or Stepwise (A–E) Way?

The mechanisms of three selected identity substitution reactions at phosphorus and sulfur occurring with stereospecific inversion have been investigated using density functional theory (DFT). The first identity reaction between methoxyl anion and methyl ethylphenylphosphinate 1 reported in 1963 has been shown to proceed in a stepwise fashion according to the addition–elimination (A–E) mechanism involving formation of a pentacoordinate phosphorus intermediate (TBI-1). In contrast, the results of DFT studies of the identity chloride exchange reaction in (ethoxy)ethylphosphonochloridothionate 3 in acetone solution provided evidence that it proceeds synchronously according to the classical Ingold’s S_N2-P mechanism. DFT calculations of the methoxyl–methoxy exchange reaction at sulfur in methyl p-toluenesulfinate 4 catalyzed by trifluoroacetic acid in methanol revealed that it proceeds stepwise (A–E mechanism), involving the formation of the high-coordinate sulfurane intermediate. In both identity transesterification reactions, 1 and 4, the transiently formed trigonal bipyramidal intermediates with the two methoxyl groups occupying apical positions (TBI-1 and TBI-4) have higher free energy barriers for the Berry-type pseudorotation than those for direct decomposition to starting phosphinate and sulfinate ensuring stereospecific inversion of configuration at the phosphinyl and sulfinyl centers. Thus, the DFT method proved its usefulness in the distinction between both mechanisms that are often indistinguishable by kinetic measurements.     

Paramagnetic Properties and Moderately RapidConformational Dynamics in the Cobalt(II) Calix[4]arene Complex by NMR

¹H NMR measurements are reported for the CD₂Cl₂/CDCl₃ solutions of the Co(II) calix[4]arenetetraphosphineoxide complex (I). Temperature dependences of the ¹H NMR spectra of I have been analyzed using the line shape analysis, taking into account the temperature variation of paramagnetic chemical shifts, within the frame of the dynamic NMR method. Conformational dynamics of the 2:1 Co(II) calix[4]arene complexes was conditioned by the pinched cone ↔pinched cone interconversion of I (with activation Gibbs energy ΔG^≠(298K) = 40 ± 3 kJ/mol. Due to substantial temperature dependence of paramagnetic shifts, complex I can be used as model compound for designing an NMR thermosensor reagent for local temperature monitoring.     

Acid–Base Equilibrium and Self-Association in Relation to High Antitumor Activity of Selected Unsymmetrical Bisacridines Established by Extensive Chemometric Analysis

Unsymmetrical bisacridines (UAs) represent a novel class of anticancer agents previously synthesized by our group. Our recent studies have demonstrated their high antitumor potential against multiple cancer cell lines and human tumor xenografts in nude mice. At the cellular level, these compounds affected 3D cancer spheroid growth and their cellular uptake was selectively modulated by quantum dots. UAs were shown to undergo metabolic transformations in vitro and in tumor cells. However, the physicochemical properties of UAs, which could possibly affect their interactions with molecular targets, remain unknown. Therefore, we selected four highly active UAs for the assessment of physicochemical parameters under various pH conditions. We determined the compounds’ pK_a dissociation constants as well as their potential to self-associate. Both parameters were determined by detailed and complex chemometric analysis of UV-Vis spectra supported by nuclear magnetic resonance (NMR) spectroscopy. The obtained results indicate that general molecular properties of UAs in aqueous media, including their protonation state, self-association ratio, and solubility, are strongly pH-dependent, particularly in the physiological pH range of 6 to 8. In conclusion, we describe the detailed physicochemical characteristics of UAs, which might contribute to their selectivity towards tumour cells as opposed to their effect on normal cells.     

箭根薯属(Tacca)苦味成分的研究-箭根酮内酯A和B的结构

从裂果薯中分得三种新型甾族苦味成分, 通过光谱解析, 推定箭根酮内酯A和B的结构前者对肿瘤细胞有抑制作用, 并对鼠疟原虫有杀灭作用.     

Direct computation of second-order SCF properties of large molecules on workstation computers with an application to large carbon clusters

Summary The ab initio SCF computation of second-order properties of large molecules (with 50 atoms or more) on workstation computers is demonstrated for static dipole polarizabilities and nuclear magneting shieldings. The magnetic shieldings are calculated on the basis of gauge including atomic orbitals (GIAO). Algorithmic advances (semi-direct algorithms with efficient integral pre-screening, and use of a quadratically convergent functional for the polarizabilities) are presented together with an illustrative application to the fullerenes C₆₀ and C₇₀.     

Theoretical studies on the infrared spectrum of the tetrahedral molecules R<Subscript>2</Subscript>MH<Subscript>2</Subscript> (R = D(H), CH<Subscript>3</Subscript>, OH; M = Ti,Zr, Hf)

Using Stuttgart/Dresden effective core potentials MWB28, MWB60, and GTO valence basis sets (8s7p6d)/[6s5p3d], (8s7p6d)/[6s5p3d] for Zr and Hf atoms and 6-311++G(3df,3pd) basis set for C, H, O, and Ti atoms, tight convergence criteria geometry optimizations and harmonic frequency calculations are performed at B3LYP and B3LYP/IEF-PCM levels of theory so as to model the gas phase and argon matrix infrared spectra of the tetrahedral molecules R₂MH₂ (R = D(H), CH₃, OH; M = Ti, Zr, Hf). Influence of the transition metal and/or substituent group on the symmetric and asymmetric stretching frequencies of the MH₂ fragment of the R₂MH₂ molecules is investigated at both the levels of theory. The modelling of the argon matrix effect improves the agreement between the calculated frequencies and the experimental ones. The calculated argon matrix to gas phase frequency shifts is compared reasonably to the experimental argon to neon matrix shifts.     

Complexes of a new series of α-diimine macrocycles,I: Template synthesis of cadmium(II) complexes of tetraazamacrocycles derived from 2,3-butanedione or benzil

Summary Cadmium(II) complexes of the type [CdL] (NO₃)₂ (whereL = tetraazamacrocycle with a 12 to 32-membered ring) have been synthesized by the reactions of 2,3-butanedione or benzil with different aliphatic diamines viz. ethylenediamine, 1,3-diaminopropane, 1,4-diaminobutane, 1,6-diaminohexane, 1,8-diaminooctane and 1,12-diaminododecane in the presence of Cd(II) as template. These complexes have been characterized by elemental analyses, conductivity measurements and IR and NMR spectral studies.

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Komplexe einer neuen Serie von -Diimin-Macrocyclen, 1. Mitt.: Synthese von Cadmium(II)-Komplexen von Tetraazamacrocyclen aus 2,3-Butandion oder Benzil

Zusammenfassung Es wurden Cadmium(II)-Komplexe des Typs [CdL] (NO₃)₂ (wobeiL einen 12-bis 32-gliedrigen Tetraazamacrocyclus darstellt) mittels der Reaktion von 2,3-Butandion oder Benzil mit verschiedenen aliphatischen Diaminen (Ethylendiamin, 1,3-Diaminopropan, 1,4-Diaminobutan, 1,6-Diaminohexan, 1,8-Diaminooctan und 1,12-Diaminododecan) hergestellt. Die Komplexe wurden mittels Elementaranalyse, Leitfähigkeitsmessungen und Infrarot- bzw. Kernresonanzspektroskopie charakterisiert.

     

The Crystallisation Kinetics of Nitrate Cancrinite Na7.6[AlSiO4]6(NO3)1.6 (H2O)2 Under Low Temperature Hydrothermal Conditions

Investigations on the formation of nitrate enclathrated cancrinite were performed under low temperature hydrothermal conditions (353 K, autogeneous pressure). The alkaline transformation of kaolinite in the presence of sodium nitrate was selected as the preferred method of synthesis. All experiments were carried out at high alkalinity, using a 16 molar NaOH solution as well as at low NaOH concentrations (2 molar NaOH). Qualitative phase analysis was performed by X-ray-powder diffraction and IR-spectroscopy. Besides cancrinite formation no further intermediate phases were formed. Quantitative data of the educt conversion into cancrinite was determined by ²⁷Al MAS NMR spectroscopy and integration of the resonance signals of four- and six-coordinated aluminium. Whereas full conversion could be found already after 24 h of reaction under highly alkaline conditions, only an insufficient progress of the reaction resulted in the case of low alkalinity.     

Combined use of nuclear magnetic resonance and infrared spectroscopy for studying recognition processes between amphenicolic antibiotics and albumin

Biological reactions are mostly concerned with selective interactions between small ligands and macromolecular receptors. The same ligands may activate responses of different intensities and/or effects in the presence of different receptors. Many approaches based on spectroscopic and non‐spectroscopic methods have been used to study interactions between small ligands and macromolecular receptors, including methods based on NMR and IR spectroscopic analysis of the solution behaviour of the ligand in the presence of receptors. In this work, we investigated the interaction between ovine serum albumin with two amphenicolic antibiotics [chloramphenicol (CAP) and thiamphenicol (TAP)], using a combined approach based on NMR and IR methodologies, furnishing complementary information about the recognition process occurring within the two systems. The two ligands, despite their similar structures, showed different affinities towards albumin. NMR methodology is based on the comparison of selective ( ) and non‐selective ( ) spin–lattice relaxation rates of the ligands in the presence and absence of macromolecular receptors and and temperature dependence analysis. From these studies, the ligand–receptor binding strength was evaluated on the basis of the ‘affinity index.’ The derivation of the affinity index from chemical equilibrium kinetics for both the CAP–albumin and TAP–albumin systems allowed a comparison of the abilities of the two amphenicolic antibiotics to interact with the protein. IR methodology is based on the comparison of the ligand–protein ‘complex’ spectra with those of the non‐interacting systems. On the basis of the differences revealed, a more thorough IR analysis was performed in order to understand the structural changes which occurred on both ligand and protein molecules within the interacting system. Copyright © 2003 John Wiley & Sons, Ltd.