Chemistry of pyrrolo[1,2-a]indole- and pyrido[1,2-a]indole-based quinone methides. Mechanistic explanations for differences in cytostatic/cytotoxic properties

In the present study we investigate pyrido[1,2-a]indole- and pyrrolo[1,2-a]indole-based quinones capable of forming quinone methide and vinyl quinone species upon reduction and leaving group elimination. Our goals were to determine the influence of the 6-membered pyrido and the 5-membered pyrrolo fused rings on quinone methide and vinyl quinone formation and fate as well as on cytostatic and cytotoxic activity. We used the technique of Spectral Global Fitting to study the fleeting quinone methide intermediate directly. Conclusions regarding quinone methide reactivity are that carbonyl O-protonation is required for nucleophile trapping and that the pKa value of this protonated species is near neutrality. The abnormally high protonated carbonyl pKa values are due to the formation of an aromatic carbocation species upon protonation. The fused pyrido ring promotes quinone methide and vinyl quinone formation but slows nucleophile trapping compared to the fused pyrrolo ring. These findings are explained by the presence of axial hydrogen atoms in the fused pyrido ring resulting in more steric congestion compared to the relatively flat fused pyrrolo ring. Consequently, pyrrolo[1,2-a]indole-based quinones exhibit more cytostatic activity than the pyrido[1,2-a]indole analogues due to their greater nucleophile trapping capability.     

Synthesis and nitration of calix[4] (aza)crowns

Calix[4] (aza) crowns containing amide groups 3a-d were synthesized by the reactions of calix[4]arene (1a) or p-tert-butylcalix[4]arene (1b) with N, N'-ethylenebis(2-chloroac-etamide) (2a) or N, N'-1,2-phenylenebis(2-chloroacetamide) (2b) by one step procedure in yields of 85-90% . Calix[4]-(aza) crowns 4a-b could be obtained by the reduction of 3a-b with LiAlH4 in yields of 51 and 67% , respectively. The nitration of 3a or 3c afforded new chromogenic calix[4]arenes 5a bearing two nitrophenol moieties and 5c bearing one nitro-phenol and one quinone moiety, respectively. The ipso-nitrations of 3b and 3d were also studied. Both gave the products containing one nitrophenol and one quinone moiety. Moreover, a very interesting calix[4]arene derivative 5d containing one cyclohexadienone moiety was also separated as the main product when 3d was ipso -nitrated.     

A computational study of unique properties of pillar[n]quinones: self-assembly to tubular structures and potential applications as electron acceptors and anion recognizers

Density functional theory has been used to calculate the thermodynamic properties and molecular orbitals of pillar[n]quinones. Pillar[n]quinones are expected to be effective electron acceptors and the ability to accept more than one electron increases with the size of the interior cavity. Pillar[5]quinone and pillar[7]quinone show a great intramolecular charge transfer upon the electron excitation from highest occupied molecular orbital (HOMO) to lowest unoccupied molecular orbital (LUMO) as indicated by a large difference of electron distributions between their HOMO and LUMO and a notable dipole moment difference between the ground and first triplet excited state. The aggregation of pillar[n]quinones leads to tubular dimeric structures joined by 2n C? H···O nonclassical hydrogen bonds (HBs) with binding energies about 2 kcal/mol per HB. The longitudinal extension of the supramolecular self‐assembly of pillar[n]quinone may be adjustable through forming and breaking their HBs by controlling the surrounding environment. The tunability of the diameter of the tubular structures can be achieved by changing the number of quinone units in the pillar[n]quinone. The electrostatic potential maps of pillar[n]quinones indicate that the positive charge in the interior cavity decreases as the number of quinone units increases. Chloride and bromide anions are chosen to examine the noncovalent anion‐π interactions between pillar[n]quinones and captured anions. The calculations show that the better compatibility of the effective radius of the anions with the interior dimension of pillar[n]quinone leads to larger stabilization energy. The selectivity of spatial matching and specific interaction of pillar[n]quinone is believed to possibly serve as a candidate for ionic and molecular recognition. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011     

Light-actuated resorcin[4]arene cavitands

A light-actuated resorcin[4]arene cavitand equipped with two quinone (Q) and two opposite Ru(II)-based photosensitizing walls was synthesized and investigated. The cavitand is capable of switching from an open to a contracted conformation upon reduction of the two Q to the corresponding SQ radical anions by intramolecular photoinduced electron transfer in the presence of a sacrificial donor. The molecular switch was investigated by cyclic and rotating disc voltammetry, UV–Vis–NIR spectroelectrochemistry, transient absorption, NMR, and EPR spectroscopy. This study provides the basis for the development of future light-activated switches and molecular actuating nanodevices.     

π-Extended Pleiadienes by [5+2] Annulation of 1-Boraphenalenes and ortho-Dihaloarenes

Palladium-catalyzed [5+2] annulation of 1-boraphenalenes with ortho-dihaloarenes afforded negatively curved π-extended pleiadienes. Two benzo[1,2-i:4,5-i’]dipleiadienes (BDPs) featuring a seven-six-seven-membered ring arrangement were synthesized and investigated. Their crystal structure revealed a unique packing arrangement and theoretical calculations were employed to shed light onto the dynamic behavior of the BDP moiety and its aromaticity. Further, a naphthalene-fused pleiadiene was stitched together by oxidative cyclodehydrogenation to yield an additional five-membered ring. This formal azulene moiety led to distinct changes in optical and redox properties and increased perturbation of the aromatic system.     

Voltammetric Behavior of 1,4‐Dimethoxypillar[m]arene[n]quinones

The electrochemical properties of a series of 1,4‐dimethoxypillar[m]arene[n]quinones (DMP[m]A[n]Qs) and the interactions between individual quinone units have been investigated on glassy carbon electrode in acetonitrile. All the quinone units showed relative electron uptake behavior except 1,4‐dimethoxypillar[5]quinones (DMP[5]Q). The results have shown that the electrochemical behavior of the DMP[m]A[n]Qs is comparatively different from that of their related linear quinone analogues. The resultant properties were attributed to the close proximity of redox‐active sites as well as the delocalization of electrons on the aromatic rings. Another aspect to be considered responsible for their electronic properties was suggested to be the electrostatic repulsions between adjacent quinone units in these complex structures. Current studies provide a better understanding on the voltammetric behavior of pillararene derivatives with different numbers of quinone units as well as their future scope in certain future electrochemical applications.     

Molecular recognition of NO/NO+ via multicenter (charge-transfer) binding to bridged diarene donors. Effect of structure on the optical transitions and complexation thermodynamics

Bridged diarenes form very strong [1:1] complexes with nitrosonium/nitric oxide in which the NO moiety is optimally sandwiched in the cleft between a pair of cofacial aromatic rings which act as a molecular "Venus flytrap". The spectral features of these associates are generally similar to those for [1:1] and [2:1] nitrosonium complexes with mononuclear alkyl-substituted benzenes, and they are appropriately described within the LCAO molecular-orbital methodology and the Mulliken (charge-transfer) formulation of donor/acceptor electronic transitions. The thermodynamics study indicates that the efficient binding is determined by (i) the close matching of the donor/acceptor redox potentials and (ii) the ability of bridged diarenes for multicentered interactions with a single NO moiety. The best fit of the electronic and structural parameters is provided by a calixarene host that allows the interacting centers to be arranged in a manner similar to those extant in [2:1] nitrosonium complexes with analogous (nonbridged) aromatic donors; this results in its very strong noncovalent binding with nitrosonium/nitric oxide with the formation constant of K(B) approximately 10(8) M(-)(1) and free-energy change of -DeltaG degrees = 45 kJ mol(-)(1). Such strong, selective, and reversible bindings of nitrosonium/nitric oxide by (cofacial) aromatic centers thus provide the basis for the development of efficient NO sensors/absorbents and also suggest their potential relevance to biochemical systems.     

Copper(II) diamino acid complexes: quantum chemical computations regarding diastereomeric effects on the energy of complexation

[reaction: see text] Quantum chemical calculations were used to rationalize the observed enantiodifferentiation in the complexation of alpha-amino acids to chiral Cu(II) complexes. Apart from Cu(II)[bond]pi interactions and steric repulsions between the anchoring cholesteryl-Glu moiety and an aromatic amino acid R group, hydrogen bonding also plays a role. In fact, in the case of tryptophan, C[double bond]O...H[bond]N hydrogen bonding between the glutamate moiety and the tryptophan N[bond]H group compensates for the loss of intramolecular hydrogen-bonding and diminished Cu(II)[bond]pi interactions.     

Structure and substitution effects on the thermotropicity of some polyesters and model compounds

Abstract

The variations which occur in the thermal stability of the nematic mesophase as a function of the structure of the mesogenic moiety are considered here for the role played by three types of modifications. These are changes in the chemical nature of the mesogenic group, variation of the axial ratio of the rigid core and the presence of lateral substituents on the aromatic rings. Low molecular weight and polymeric liquid crystals of similar chemical nature have been investigated in order to see if parallel structure—property relationships exist between the two groups of compounds. In particular, starting from a mesogenic group built up of three aromatic rings connected by ester bonds, we have introduced the following modifications: (i) substitution of the central —COOC₆H₄OOC—with the—CH[dbnd]N—N[dbnd]CH— group; (ii) addition of two oxybenzoic end units to increase the length of the mesogenic moiety; (iii) introduction of two or more lateral methoxy substituents on the aromatic rings. The compounds were obtained by low temperature solution esterification between acyl chlorides and phenolic derivatives in the presence of a tertiary amine. Syntheses generally took place through the preliminary preparation of suitable intermediates. The thermal stability and the nature of the mesophases have been examined by different techniques. An interpretation of the results on the basis of the axial ratio and the strength of orientation dependent mutual attractions is attempted for model compounds. As far as polymers are concerned thermodynamic parameters follow the expected trend, if compared with those of low molecular weight analogues. Qualitatively models and polymers exhibit a similar dependence of mesophase stability on geometrical and electronic effects.     

超分子体系中的分子识别研究 5: 单-[6-(1-吡啶)-6-脱氧]-α-和γ-环糊精对氨基酸分子识别的热力学性质

本文用分光光度滴定法测定了单-[6-(1-吡啶)-6-脱氧]-α-和γ-环糊精(1)和(3)与一系列氨基酸在磷酸缓冲溶液中(pH=7.20), 25.0~40.0℃时形成超分子体系的稳定常数, 进而计算了配位焓和配位熵, 并与单-[6-(1-吡啶)-6-脱氧]-β-环糊精(2)的实验结果作了比较。化学计量法表明,所有的氨基酸均与环糊精衍生物形成了1:1的超分子体系。从热力学的观点,讨论了化学修饰环糊精和客体氨基酸的尺寸或形状适合、疏水效应、范德华力和氢键等几种弱相互作用对形成超分子体系的贡献。研究结果发现, 具有正电荷环糊精衍生物的吡啶基, 作为一种分子探针不仅可以识别氨基酸生物分子的尺寸或形状之间的差异, 而且还可以识别L/D-型手性对映体之间的差异, 进一步表明了主-客体间的诱导楔合、几何互补在分子受体选择性键合底物形成超分子体系中的重要作用。     

Cinnamoyl shikonin

The title compound, 1-(5,8-di­hydro-1,4-di­hydroxy-5,8-dioxo-2-naphthyl)-4-methyl­pent-3-en-1-yl cinnamate, C₂₅H₂₂O₆, crystallizes in space group P2₁. The phenyl ring of the cinnamate is anti to the carbonyl group of the same moiety [C—C—C—C = −175.6 (2)°] and is nearly parallel to the naphthyl ring system. Two six-membered rings formed by intramolecular hydrogen bonds, with O—H⃛O distances of 2.587 (2) and 2.589 (2) Å, occur on either side of the fused ring system, creating a tetracyclic pyrene-shaped system. The phenyl ring forms an intermolecular stack with the benzo­quinone ring, as a result of aromatic π–π interactions.     

Sterically encumbered diphosphaalkenes and a bis(diphosphene) as potential multiredox-active molecular switches: EPR and DFT investigations

The reduction products of two diphosphaalkenes (1 and 2) and a bis(diphosphene) (3) containing sterically encumbered ligands and corresponding to the general formulas Ar-X=Y-Ar'-Y=X-Ar, have been investigated by EPR spectroscopy. Due to steric constraints in these molecules, at least one of the dihedral angles between the CXYC plane and either the Ar plane or the Ar' plane is largely nonzero and, hence, discourages conformations that are optimal for maximal conjugation of P=X (or P=Y) and aromatic pi systems. Comparison of the experimental hyperfine couplings with those calculated by DFT on model systems containing no cumbersome substituents bound to the aromatic rings shows that addition of an electron to the nonplanar neutral systems causes the X=Y-Ar'-Y=X moiety to become planar. In contrast to 1 and 2, 3 can be reduced to relatively stable dianion. Surprisingly the two-electron reduction product of 3 is paramagnetic. Interpretation of its EPR spectra, in the light of DFT calculations on model dianions, shows that in [3](2)(-) the plane of the Ar' ring is perpendicular to the CXYC planes. Due to interplay between steric and electronic preferences, the Ar-X=Y-Ar'-Y=X-Ar array for 3 is therefore dependent upon its redox state and acts as a "molecular switch".     

Simple electrooptical sensors for inorganic anions

[reaction: see text] Electrooptical sensors consisting of a conjugated chromophore undergoing a change in color and a redox-active moiety such as quinone fused to the chromophore were synthesized. Strong changes in colorimetric and electrochemical properties were observed in the presence of inorganic anions. A unique anion-specific response was observed for fluoride, pyrophosphate, and acetate. DFT (B3LYP/6-31G) calculations performed for both "on/off" states of a sensor-fluoride model are in good agreement with the observed electrochemical and spectroscopic data.     

Design and synthesis of spirobiisoxazoline dibenzoquinone derivatives via [3 + 2] double 1,3-dipolar cycloaddition reaction

“A series of novel spirobiisoxazoline dibenzoquinone derivatives were synthesized starting from 2,5-dimethoxybenzaldehyde in a six-step synthetic sequence”. The key step [3?+?2] double 1,3-dipolar cycloaddition of oxime chloride with allenoate was performed under mild reaction conditions using sodium carbonate at ambient temperature. This is the first innovative synthesis of Spirobiisoxazoline Dibenzoquinone system where quinone ring is alkylated to isoxazoline moiety.     

Oxygen reduction catalysis at anthraquinone centres molecularly wired via carbon nanotubes

Multi-walled carbon nanotubes (MWCNTs) have been chemically derivatised via the reduction of anthraquinone-1-diazonium chloride with hypophosphorous acid to attach 1-anthraquinonyl groups to the MWCNTs, most likely at edge plane like defects. The covalently attached quinone moiety attached to the nanotubes (‘molecular wire’) acts as an effective mediator for the electrocatalytic reduction of oxygen.     

Molecular mechanical devices based on quinone-pyrrole and quinone-indole dyads: a computational study

A set of intramolecularly connected dyads consisting of a quinone unit and a pyrrole or indole moiety have been designed and evaluated in quantum-chemical calculations. It is shown computationally for several systems, depending on the length and attachment points of the interconnecting chains, that a reduction of the quinone to the semiquinone radical anion or quinolate dianion state leads to a reversible intramolecular reorientation from a pi-stacked to a T-stacked arrangement. In the rearranged structures, a hydrogen bond from the pyrrole or indole N-H function to the semiquinone or quinolate pi-system is created upon reduction. In some systems, hydrogen bonds to the semiquinone or quinolate oxygen atoms are partly feasible and will be preferred over T-stacking. The choice of systems has been based on recent computational observations related to photosystem I. Systems with pyrrole or indole units should provide a better basis for the envisioned molecular motor than recently proposed quinone-benzene dyads. The intramolecular interactions modify the quinone redox potentials. Electronic g-tensors have been computed for the semiquinone states. These reflect characteristically the presence and nature of hydrogen bonds to the semiquinone and represent suitable electron paramagnetic resonance spectroscopic probes for the preferred structures. Intramolecular proton transfer is possible in the dianionic state.     

Surface‐Bound Cucurbit[8]uril Catenanes on Magnetic Nanoparticles Exhibiting Molecular Recognition

We demonstrate the preparation of surface‐bound cucurbit[8]uril (CB[8]) catenanes on silica nanoparticles (NPs), where CB[8] was employed as a tethered supramolecular “handcuff” to selectively capture target guest molecules. In this catenane, CB[8] was threaded onto a methyl viologen (MV²⁺) axle and immobilized onto silica NPs. The formation of CB[8] catenanes on NPs were confirmed by UV/Vis titration experiments and lithographic characterization, demonstrating a high density of CB[8] on the silica NPs surface, 0.56 nm^?2. This CB[8] catenane system exhibits specific molecular recognition towards certain aromatic molecules such as perylene bis(diimide), naphthol and aromatic amino acids, and thus it can act as a nanoscale molecular receptor for target guests. Furthermore, we also demonstrate its use as an efficient and recyclable nano‐platform for peptide separation. By embedding magnetic NPs inside silica NPs, separation could be achieved by simply applying an external magnetic field. Moreover, the peptides captured by the catenanes could be released by reversible single‐electron reduction of MV²⁺. The entire process demonstrated high recoverability.     

Silicon–Heteroaromatic [FeFe] Hydrogenase Model Complexes: Insight into Protonation,Electrochemical Properties,and Molecular Structures

To learn from Nature how to create an efficient hydrogen‐producing catalyst, much attention has been paid to the investigation of structural and functional biomimics of the active site of [FeFe]‐hydrogenase. To understand their catalytic activities, the μ‐S atoms of the dithiolate bridge have been considered as possible basic sites during the catalytic processes. For this reason, a series of [FeFe]‐H₂ase mimics have been synthesized and characterized. Different [FeFe]‐hydrogenase model complexes containing bulky Si–heteroaromatic systems or fluorene directly attached to the dithiolate moiety as well as their mono‐PPh₃‐substituted derivatives have been prepared and investigated in detail by spectroscopic, electrochemical, X‐ray diffraction, and computational methods. The assembly of the herein reported series of complexes shows that the μ‐S atoms can be a favored basic site in the catalytic process. Small changes in the (hetero)‐aromatic system of the dithiolate moiety are responsible for large differences in their structures. This was elucidated in detail by DFT calculations, which were consistent with the experimental results.     

Determination of the geometry change of the phenol dimer upon electronic excitation.

The change of the phenol dimer (PH2) structure upon electronic excitation is determined by a Franck-Condon analysis of the intensities in the fluorescence emission spectra obtained via excitation of seven different vibronic bands. A total of 547 emission band intensities are fitted, together with the changes of rotational constants upon electronic excitation of fi ve isotopomers. These rotational constants are taken from previously published [Schmitt et al. ChemPhysChem 2006, 7, 1241-1249] high-resolution LIF measurements. The geometry change upon electronic excitation of the pipi* state of the donor moiety can be described by a strong shortening of the hydrogen bond, a shortening of the CO bond in the donor moiety, an overall symmetric expansion of the donor phenol ring, and a nearly unchanged acceptor moiety. The resulting geometry changes are interpreted on the basis of ab initio calculations.