RESUMO
Herein, various molecular balances used for comparing the strengths of intramolecular noncovalent interactions are reviewed. Our overview indicates that considerable quantitative insight into the strength of noncovalent interactions can be gained through the careful design of molecular balances. Many exciting opportunities certainly exist for the design of further new balances to quantify and dissect the relative strengths of noncovalent interactions as a function of solvation and the importance of the many factors that contribute to overall molecular recognition. However, even simple model molecules can show a multiplicity of intramolecular noncovalent interactions acting in a combined fashion. It is therefore essential to undertake a detailed computational analysis to identify all possible noncovalent interactions present in a selected molecular balance prior to a quantitative experimental assessment of the strength of a particular noncovalent interaction. It is also argued that the words "torsion" and "molecular balance" seem to have become inextricably linked and, in consequence, even top pan and seesaw balances have been mistakenly referred to in these terms.
RESUMO
The relative strength of noncovalent interactions between a thioether sulfur atom and various π systems in designed top pan molecular balances was determined by NMR spectroscopy. Compared to its oxygen counterpart, the sulfur atom displays a remarkable ability to interact with almost equal facility over the entire range of π systems studied, with the simple alkene emerging as the most powerful partner. With the exception of the Oâ â â heteroarene interaction, all noncovalent interactions of sulfur with π systems are favoured over oxygen.
RESUMO
A comparative study using NMR spectroscopy and designed top-pan molecular balances demonstrates that the noncovalent interaction of a hydroxy group with π-deficient pyrazine and quinoxaline units involves a lone pair-heteroarene interaction which is much stronger and solvent independent when measured relative to the classical π-facial hydrogen bond to a benzene ring. Alkyl fluorides also prefer the heteroarene rings over the benzene ring. The attractive interaction between a quinoxaline and a terminal alkyne is also stronger than the intramolecular hydrogen bond to an arene.
Assuntos
Ácidos Heterocíclicos/química , Espectroscopia de Ressonância Magnética/métodos , Ligação de Hidrogênio , Modelos MolecularesRESUMO
A comparative study of molecular balances by NMR spectroscopy indicates that noncovalent functional-group interactions with an arene dominate over those with an alkene, and that a π-facial intramolecular hydrogen bond from a hydroxy group to an arene is favored by approximately 1.2â kJ mol(-1). The strongest interaction observed in this study was with the cyano group. Analysis of the series of groups CH2CH3, CH=CH2, C≡CH, and C≡N shows a correlation between conformational free-energy differences and the calculated charge on the C(α) atom of these substituents, which is indicative of the electrostatic nature of their πâ interactions. Changes in the free-energy differences of conformers show a linear dependence on the solvent hydrogen bond acceptor parameter ß.
Assuntos
Alcenos/química , Hidrocarbonetos/química , Modelos MolecularesRESUMO
Carboxylate anions, dianions and ester enolates provide simultaneous protection and activation for directed carbometalation reactions. Advantage can be taken of the bis-carbanionic character of the intermediate for further controlled C-C bond forming reactions.
RESUMO
Easy as 1,2,3: Reaction of methyl carbamate, triethyl orthoformate, and readily available alkenes provides a highly practical preparation of protected aminocyclopropanes. The reaction proceeds with preferential cis addition to alkenes, and cleavage of the methyl carbamate gives the free aminocyclopropanes as their HI salts.
Assuntos
Cobre/química , Ciclopropanos/química , Alcenos , Catálise , Estrutura Molecular , EstereoisomerismoRESUMO
The hypoxic response in humans is regulated by the hypoxia-inducible transcription factor system; inhibition of hypoxia-inducible factor (HIF) activity has potential for the treatment of cancer. Chetomin, a member of the epidithiodiketopiperazine (ETP) family of natural products, inhibits the interaction between HIF-alpha and the transcriptional coactivator p300. Structure-activity studies employing both natural and synthetic ETP derivatives reveal that only the structurally unique ETP core is required and sufficient to block the interaction of HIF-1alpha and p300. In support of both cell-based and animal work showing that the cytotoxic effect of ETPs is reduced by the addition of Zn(2+) through an unknown mechanism, our mechanistic studies reveal that ETPs react with p300, causing zinc ion ejection. Cell studies with both natural and synthetic ETPs demonstrated a decrease in vascular endothelial growth factor and antiproliferative effects that were abrogated by zinc supplementation. The results have implications for the design of selective ETPs and for the interaction of ETPs with other zinc ion-binding protein targets involved in gene expression.
Assuntos
Dissulfetos/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Alcaloides Indólicos/farmacologia , Zinco/farmacologia , Fatores de Transcrição de p300-CBP/metabolismo , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dissulfetos/química , Relação Dose-Resposta a Droga , Células HCT116 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/química , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Alcaloides Indólicos/química , Modelos Químicos , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Molecular , Ligação Proteica/efeitos dos fármacos , Estrutura Terciária de Proteína , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade , Fator A de Crescimento do Endotélio Vascular/metabolismo , Zinco/química , Fatores de Transcrição de p300-CBP/química , Fatores de Transcrição de p300-CBP/genéticaRESUMO
Selective examples of OH...arene, NH2...arene and C-HN[triple bond, length as m-dash]C weak interactions are presented using a flexible dibenzobicyclo[3.2.2]nonane scaffold for detection and comparative characterisation of non-covalent interactions in solution and solid states.
RESUMO
The first N2 complex stabilised by N-heterocyclic carbene ligands, Fe(C-N-C)(N2)2, has been obtained by the reduction of Fe(C-N-C)Br2 where C-N-C = 2,6-bis(aryl-imidazol-2-ylidene)pyridine, aryl = 2,6-Pr(i)2C6H3, with Na(Hg); it serves as a convenient precursor for other iron NHC 'pincer' complexes of the type Fe(C-N-C)(N2)L where L = C2H4, PMe3 and Fe(C-N-C)(CO)2.
RESUMO
Amidocyclopropanes are readily prepared by reaction of N-diethoxymethyl amides with alkenes in the presence of zinc amagalm, zinc chloride and chlorotrimethylsilane.
RESUMO
A binding site optimisation protocol for the design of artificial enzymes based on "small molecule-small molecule" binding studies by diffusion NMR is presented. Since the reaction chosen was the hydrolysis of ester 1 ([4-(4-carboxy-1-oxobutyl)-aminobenzyl]-phenethyl ester), an analogous phosphonate ester 2 ([4-(4-carboxy-1-oxobutyl)-aminobenzyl]-phosphonic phenethyl ester) was selected as a suitable transition state analogue (TSA). The key objective of the NMR studies was to find a unit with functional groups capable of binding to the acidic sites of the TSA. Nine dipeptides, mainly with basic and hydroxyl groups, were used and their affinity to the TSA was studied by measuring the change in the diffusion coefficient, D(pep), upon binding by pulse field gradient NMR. The value of D(pep) at 298 K in D(2)O at pD 5, 7 and 10 was measured both in free solution, and mixtures containing one dipeptide and the TSA. As both components are low molecular weight species with M < 500, a TSA-to-dipeptide ratio of 10:1 was used to detect significant changes in D(pep). The results revealed that dipeptides with basic residues show higher affinity to the TSA than those with hydroxyl or aliphatic side chains in aqueous solutions. The dipeptide showing the most significant relative change in D(pep) was H-Arg-Arg-OH, and the binding constant was estimated to be 86 L M(-1) by measuring D(pep) at varying concentrations of the TSA. In addition, binding of the TSA to a new water-soluble polymer with a polyallylamine backbone and randomly distributed Arg-Arg binding sites was examined, and the binding constant was estimated to be > or =1500 L M(-1). As confirmed by further catalytic activity tests, polymers containing Arg-Arg as a binding site are capable of significant rate accelerations in the hydrolysis of ester 1.
Assuntos
Materiais Biomiméticos/química , Dipeptídeos/química , Enzimas/química , Ésteres/química , Ressonância Magnética Nuclear Biomolecular/métodos , Sequência de Aminoácidos , Sítios de Ligação , Materiais Biomiméticos/metabolismo , Catálise , Difusão , Dipeptídeos/metabolismo , Enzimas/metabolismo , Ésteres/metabolismo , Hidrólise , Especificidade por SubstratoRESUMO
A three component reaction involving an isocyanide, a carboxylic acid and an epoxide or aziridine is described.
RESUMO
Tertiary allylic thionitrites undergo thermal rearrangement to alpha,beta-episulfide nitroso dimers via ring closure of allylthiyl radicals.