Synthesis of Oligonucleotides containing the cis-Interstrand Crosslink Produced by Mitomycins in their Reaction with DNA.

Mitomycin C (MC) an antitumor drug and decarbamoylmitomycin C (DMC), a derivative of MC lacking the carbamoyl moiety, are DNA alkylating agents which can form DNA interstrand crosslinks (ICLs) between deoxyguanosine residues located on opposing DNA strands. MC forms primarily deoxyguanosine adducts with a 1"-R stereochemistry at the guanine-mitosene bond (1"-α, trans) whereas DMC forms mainly adducts with a 1"-S stereochemistry (1"-β, cis). The crosslinking reaction is diastereospecific: trans-crosslinks are formed exclusively at CpG sequences, while cis-crosslinks are formed only at GpC sequences.

Synthesis of Mitomycin C and decarbamoylmitomycin C N deoxyadenosine-adducts.

Mitomycin C (MC), an anti-cancer drug, and its analog, decarbamoylmitomycin C (DMC), are DNA-alkylating agents. MC is currently used in the clinics and its cytotoxicity is mainly due to its ability to form Interstrand Crosslinks (ICLs) which impede DNA replication and, thereby, block cancer cells proliferation. However, both MC and DMC are also able to generate monoadducts with DNA.

A Versatile Bis-Allylboron Reagent for the Stereoselective Synthesis of Chiral Diols.

Allylboron reagents are popular in synthesis owing to their versatility and the predictable stereochemical outcomes of their reactions with carbonyl compounds. Herein, we describe the synthesis of (Z,Z)-hexadienyl bis-boronate 1, a configurationally stable, crystalline, and easy to handle compound, which represents a class of bis-allylic boron reagents with heretofore untapped synthetic potential. In combination with a chiral phosphoric acid catalyst, the reagent can be employed for the enantioselective allyl transfer reaction to a variety of one-pot transformations, enabling swift access to functionalized 1,n-diols.

Comparative analysis of condom lubricants on pre & post-coital vaginal swabs using AccuTOF-DART.

In this study we demonstrate the use of Direct Analysis in Real Time Mass Spectrometry (DART) as a powerful tool for detection of nonoxynol in vaginal fluid post contact with a condom, enabling rapid tracing and added evidences in sexual assault crimes. Vaginal fluid was sampled using cotton swabs and glass rods and measured directly with DART. Sample preparation using water, hexane, methanol, and dichloromethane extraction, was explored for comparison and optimization of signals.

Circular dichroism analysis of the calicheamicin-DNA interaction revisited.

Calicheamicin, γ, is a remarkable DNA binding-cleaving, enediyne-containing, natural product that exhibits potent antitumor activity. In this study, we used electronic circular dichroism spectroscopy to monitor potential drug-induced DNA conformational changes and DNA induced conformational changes in the calicheamicin aglycone. Three DNA dodecamer sequences were examined: one containing a primary TCCT binding/cleavage site and two dodecamers containing less prominent CTCT and TCTC sites.

Chiral tetranuclear and dinuclear copper(ii) complexes for TEMPO-mediated aerobic oxidation of alcohols: are four metal centres better than two?

The one-pot reaction of 3,5-di-tert-butyl-2-hydroxybenzaldehyde, (R)-2-aminoglycinol and Cu(OAc)2·2H2O in a 1 : 1 : 1 ratio in the presence of triethylamine led to the isolation of X-ray quality crystals of the chiral complex (R)- in high yield. The single crystal structure of (R)- reveals a tetranuclear copper(ii) complex that contains a {Cu4(μ-O)2(μ3-O)2N4O4} core. A reaction using (1S,2R)-2-amino-1,2-diphenylethanol as precursor under the same conditions generated the chiral complex (S,R)-; its structure was determined by single crystal X-ray crystallography and was found to contain a {Cu2(μ-O)2N2O2} core.

A direct stereoselective preparation of a fish pheromone and application of the zinc porphyrin tweezer chiroptical protocol in its stereochemical assignment.

A two-step stereoselective preparation of a goldfish pheromone, 17α,20β-dihydroxy-4-pregnen-3-one, is reported from the readily available cortexolone in 64% overall yield. The (20S)-epimer was also synthesized in three steps from cortexolone with an overall yield of 47%. A microscale chiroptical technique based on a host/guest complexation mechanism between the substrate and a dimeric metalloporphyrin host (tweezer) was used to confirm the stereochemical assignment, while Density Functional Theory (DFT) calculations were employed to explain the high stereoselectivity induced by the 17α-hydroxyl and C18-methyl groups.

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.

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.

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.

A review of forensic science higher education programs in the United States: bachelor's and master's degrees.

As the number of forensic science programs offered at higher education institutions rises, and more students express an interest in them, it is important to gain information regarding the offerings in terms of courses, equipment available to students, degree requirements, and other important aspects of the programs. A survey was conducted examining the existing bachelor's and master's forensic science programs in the U.S.

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.

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 guest's 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.

CD-sensitive Zn-porphyrin tweezer host-guest complexes, part 2: cis- and trans-3-hydroxy-4-aryl/alkyl-beta-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.

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.

Ab initio studies of receptor interactions with AMPA ((S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl) propionic acid) and kainic acid (2S-(2 alpha, 3 beta, 4 beta))-2-carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid.

The optimum geometries and binding energies of the complexes formed by AMPA and Kainic acid, as well as their anions with tyrosine, proline and some tripeptides are investigated with quantum chemical calculations (HF/6-31G**). It was found that receptors featuring the Tyr-Ala-Pro sequence exhibit stronger binding energies to the substrates than the Tyr-Ser-Pro and Tyr-Ser-Ser. As expected, the anions are more bound than the neutral species.

Amino acid alanine reactivity with the fingerprint reagent ninhydrin. A detailed ab initio computational study.

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 Ruhemann's Purple. A computational study of the mechanisms and reaction energetics of the formation of Ruhemann's Purple from ninhydrin and alanine is presented.

Synthesis and circular dichroism of tetraarylporphyrin-oligonucleotide conjugates.

The preparation and circular dichroic (CD) studies of self-complimentary 8-mer DNA sequences with a porphyrin at the 3' end are presented. Electronic interaction between the two porphyrins (the interchromophoric distance is in the range of 28-40 A), attached to both ends of the double-stranded helix, gives rise to a long-range exciton-coupled CD in the visible region (400-450 nm). The porphyrin chromophores act as sensitive probes of geometrical changes in the DNA backbone and sensitively reflect the double-strand to single-strand transition.

Porphyrin substituted phosphoramidites: new building blocks for porphyrin-oligonucleotide syntheses.

Thymidine phosphoramidites containing trispyridylphenyl and tetraphenylporphyrin chromophores attached via a short amide linker in the 3'-position have been synthesized and used as building blocks in solid-phase synthesis of self-complementary 8-mer oligonucleotides 3'-T-5'-GCGCGCA-3' and 5'-ACGCGCGT-3'. To our knowledge, these are the first porphyrin-oligonucleotide conjugates carrying the porphyrin chromophores in the 3'-position. Chain assembly was achieved by automated solid-phase synthesis and by inexpensive straightforward 'in flask' modification of commercially available solid supported oligonucleotides.

Detection of zinc ions by differential circularly polarized fluorescence excitation.

A new chiroptical spectroscopic approach, differential circularly polarized fluorescence excitation (CPE), can be used to provide a selective method for detecting the presence of zinc ions. The approach utilizes the same instrumentation as fluorescence-detected circular dichroism and provides strong contrast in metal detection due to response to both chelation-enhanced fluorescence and circular dichroism upon metal ion binding. The observed contrast is therefore better than either of the parent spectroscopic detection methods.

Magnesium tetraarylporphyrin tweezer: a CD-sensitive host for absolute configurational assignments of alpha-chiral carboxylic acids.

A protocol to determine the absolute configuration of alpha-chiral carboxylic acids based on a modified circular dichroic (CD) exciton chirality method has been developed. The protocol relies on a host-guest complexation mechanism: the chiral substrates are derivatized to give bifunctional amide conjugates ("guests") that form complexes with a dimeric magnesium porphyrin host, Mg-T (T stands for "tweezer") that acts as a "receptor". The two porphyrins in the complex adopt a preferred helicity dictated by the substituents at the chiral center in accordance with their steric sizes (assigned on the basis of conformational energy A-values) and, consequently, with the absolute configuration of the substrates under investigation.

Configurational assignment of alpha-chiral carboxylic acids by complexation to dimeric Zn-porphyrin: host-guest structure, chiral recognition and circular dichroism.

A circular dichroic (CD) excition chirality method based on host-guest chiral recognition has been developed to determine the absolute configuration of carboxylic acids with an alpha-stereogenic center; an amide C = O-->Zn coordination, identified by infrared spectroscopy and computations, is involved in this complexation.

Induction of Cholesteric Mesophases by Simple Cyclic Derivatives of p,p'-Disubstituted 1,2-Diphenylethane-1,2-diols: Importance of Shape and Polarizability Effects.

A systematic study of the cholesteric induction in nematic solvents (MBBA and E7) by some cyclic derivatives of unsubstituted and p,p'-disubstituted-1,2-diphenylethane-1,2-diols shows that the values of the twisting power are significantly dependent on the nature of the link connecting the two oxygen atoms and on the nature of the p,p'-substituents. This result has been interpreted considering that the nature of the bridge affects the overall molecular shape and the p,p'-substituents affect both the molecular polarizability and shape. This investigation points out that the polarizability of the solute and the solvent is the main parameter in determining the value of the twisting power while electrostatic arene-arene interactions contribute to a less extent.