Gloria Proni

Probing molecular chirality by CD-sensitive dimeric metalloporphyrin hosts.

This feature article reviews dimeric metalloporphyrin hosts employed as chirality probes in chiral recognition processes involving synthetic compounds and natural products. Upon formation of a chiral host-guest supramolecular complex between an achiral bis-metalloporphyrin derivative and a chiral non-racemic guest, a CD response occurs in the porphyrin spectral region, which is diagnostic of the guests absolute configuration. Several bis-porphyrin hosts used in the stereochemical investigation of organic compounds are described and the scope of their application as chirality probes critically assessed. The review encompasses the description of structural features of the host-guest complexes, the nature of the chirality transfer mechanism and the practical application in solving stereochemical problems. In particular, with reference to the method based on bis-porphyrin tweezers, we describe recent advances based on the use of molecular modeling, which have broadened the applicability of the tweezer methodology and allowed extraction of deeper structural information contained in the experimental CD data.

Bioactive A-Type Proanthocyanidins from Cinnamomum cassia

Two trimeric proanthocyanidins, cinnamtannin B-1 (1) and cinnamtannin D-1 (2), have been isolated from the bark of Cinnamomum cassia along with the known tetramer parameritannin A-1 (3) and a previously unreported tetramer, named cassiatannin A (4). The structures of 1-4 were elucidated on the basis of 1D and 2D NMR, MS, and CD analyses and compared to the reported data. Proanthocyanidins (1-4) possess significant in vitro inhibitory activity against cyclooxygenase-2 (COX-2) at micromolar concentrations.

Supramolecular Detection of Metal Ion Binding: Ligand Conformational Control of Cholesteric Induction in Nematic Liquid Crystalline Phases

Tripodal tetradentate ligands may act as chemosensor molecules. Their ability to torque a nematic into a cholesteric phase increases upon complexation with copper ion. Moreover, changes in overall shape of the complexes induced by different metals and counter ions were transferred sensitively to the supramolecular level, observed by proportionate changes in the degree of twisting. Modification of the oxidation state of the metal center also gave large changes in twisting power; this suggests potential application in electrochemical molecular switches. The handedness of the induced cholesteric phase is related to the stereochemistry of the ligand: The small amount of chiral dopant needed for the LC technique (less than 2 nmol) suggests the possible determination of the absolute configuration of the parent primary amines of the ligands.

Bulky melamine-based Zn-porphyrin tweezer as a CD probe of molecular chirality†‡

The transfer of chirality from a guest molecule to an achiral host is the subject of significant interest especially when, upon chiral induction, the chiroptical response of the host/guest complex can effectively report the absolute configuration (AC) of the guest. For more than a decade, dimeric metalloporphyrin hosts (tweezers) have been successfully applied as chirality probes for determination of the AC for a wide variety of chiral synthetic compounds and natural products. The objective of this study is to investigate the utility of a new class of melamine-bridged Zn-porphyrin tweezers as sensitive AC reporters. A combined approach based on an experimental CD analysis and a theoretical prediction of the prevailing interporphyrin helicity demonstrates that these tweezers display favorable properties for chiral recognition. Herein, we discuss the application of the melamine-bridged tweezer to the chiral recognition of a diverse set of chiral guests, such as 1,2-diamines, α-amino-esters and amides, secondary alcohols, and 1,2-amino-alcohols. The bulky periphery and the presence of a rigid porphyrin linkage lead, in some cases, to a more enhanced CD sensitivity than that reported earlier with other tweezers.

CD‐sensitive Zn‐porphyrin tweezer host‐guest complexes, part 2: Cis‐ and trans‐3‐hydroxy‐4‐aryl/alkyl‐β‐lactams. A case study

This article describes an application of the host-guest chiral recognition approach called tweezer methodology for the determination of the absolute configuration of 3-hydroxy-beta-lactams. These substrates represent challenging cases due to their chemical reactivity, the presence of multiple stereogenic centers and several functional groups which offer various possibilities of binding to the Zn-porphyrin host. OPLS-2005, the force field used in this work to predict the interporphyrin twist, modeled correctly the host-guest complexation mechanism and revealed conformational details of the bound substrates. The computational study also suggested that in cases where an increase in the magnitude of the stereodifferentiation and an intense experimental CD are observed, the bound conformation of the conjugates are hydrogen bonded. The present investigation provides evidence that when the tweezer method is assisted by the OPLS-2005 based computational approach, it can be successfully applied to the configurational and conformational elucidation of multi-functional compounds with multiple stereogenic centers.

Epiafzelechin from the Root Bark of Cassia sieberiana: Detection by DART Mass Spectrometry, Spectroscopic Characterization, and Antioxidant Properties

The root bark of Cassia sieberiana was analyzed using direct analysis in real time mass spectrometry, and a main flavonoid component with an [M + H](+) mass of 275 was identified. The flavonoid, epiafzelechin, was isolated and fully characterized with the concerted use of NMR spectroscopy, circular dichroism, and optical rotation. Electronic circular dichroism and optical rotation TDDFT calculations were also performed, and their agreement with the experimental results confirmed the enantiomeric identity of the isolated natural product. The antioxidant activity of the compound was also investigated.

CD‐sensitive Zn‐porphyrin tweezer host‐guest complexes, part 1: MC/OPLS‐2005 computational approach for predicting preferred interporphyrin helicity

This article describes a computational study on dimeric zinc porphyrin tweezer complexes with primary/secondary amines and secondary alcohols that validates the use of Optimized Potential for Liquid Simulations (OPLS-2005) as the lead computational choice for assisting the tweezer methodology in the absolute configurational assignment of organic compounds. A supramolecular, microscale approach known as the tweezer method has been widely applied in the past decade for determining the absolute configuration of chiral substrates that are difficult to study by other readily available methods. The method relies on a host/guest complexation mechanism between a porphyrin tweezer moiety and a substrate, after its conversion into a bidentate conjugate. The formation of 1:1 complexes is a stereodifferentiating process: upon complexation, the originally achiral tweezer adopts a preferential interporphyrin helicity, dictated by the absolute configuration of the chiral substrate. By correctly predicting the sign of the interporphyrin helicity in the complex, OPLS-2005 provides a correlation between the observed circular dichroism (CD) signal and the absolute configuration of the substrate. It also offers a great degree of insight into the structural factors responsible for chiral recognition and the amplitude of exciton couplets. Moreover, the preferential binding sites between the Zn-tweezer and secondary amine conjugates were revealed by using the new computational approach.

The chirality of the cholesteric phases of DNA and G-wires: its connection to their molecular structures.

While the handedness of the cholesteric phases formed by assembled guanosine derivatives (G-wires) follow the correlation right-handed helices-->right-handed cholesterics (left-handed -->left-handed), the cholesteric phase formed by B-DNA (right-handed helix) is left-handed. This apparent discrepancy is overcome by considering pitch (p) variations with temperature. Plots of p(-1) versus T(-1) have, in fact, the same trend (positive intercept and negative slope) in the case of right-handed G-wires and B-DNA, while for the left-handed G-wire of deoxyguanosine monophosphate (dGMP), the opposite behavior is observed (negative intercept and positive slope). Therefore, the relation between molecular handedness and cholesteric helicity cannot, in general, be assessed by using measurements based on a single temperature; hence the temperature variation of the cholesteric parameters should be investigated. In all cases there is no remarkable salt effect on the cholesteric parameters.

Identification and quantitation of 3,4-methylenedioxy-N-methylamphetamine (MDMA, ecstasy) in human urine by 1H NMR spectroscopy. Application to five cases of intoxication

Identification of 3,4-methylenedioxy-N-methylamphetamine (MDMA, ecstasy) in five cases of intoxication using nuclear magnetic resonance (NMR) spectroscopy of human urine is reported. A new water suppression technique PURGE (Presaturation Utilizing Relaxation Gradients and Echoes) was used. A calibration curve was obtained using spiked samples. The method gave a linear response (correlation coefficient of 0.992) over the range 0.01-1mg/mL. Subsequently, quantitation of the amount of MDMA present in the samples was performed. The benefit and reliability of NMR investigations of human urine for cases of intoxication with MDMA are discussed.

Amino Acid Alanine Reactivity with the Fingerprint Reagent Ninhydrin. A Detailed Ab Initio Computational Study

ABSTRACT: Ninhydrin is one of the most widely used reagents for chemical development of fingerprints on porous surfaces. The detection is based on the reaction of ninhydrin with a monoacidic component of the fingerprint to form an intensively colored compound named Ruhemanns Purple. A computational study of the mechanisms and reaction energetics of the formation of Ruhemanns Purple from ninhydrin and alanine is presented. Such a study is significant from a forensic science point of view because of the strong interest in the forensic chemistry and law enforcement communities in developing alternatives to the current generation of ninhydrin like chemicals for the detection and development of latent fingerprints. Information about the mechanism of reaction between ninhydrin and amino acids can ultimately help to design compounds with stronger chromo‐fluorogenic properties in aid of detecting fingerprints at crime scenes. The three most accepted mechanisms of formation have been considered using ab initio quantum mechanical calculations. At relatively high temperature (∼100°C) all three mechanisms are energetically feasible. However since it is recommended that forensic analyses be performed at room temperature, a revised mechanism is proposed for the formation of Ruhemanns Purple under this condition.