Electrochemistry represents one of the most intimate ways of interacting with molecules. This review discusses advances in synthetic organic electrochemistry since 2000. Enabling methods and synthetic applications are analyzed alongside innate advantages as well as future challenges of electroorganic chemistry.

Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance

Natural products have been a rich source of compounds for drug discovery. However, their use has diminished in the past two decades, in part because of technical barriers to screening natural products in high-throughput assays against molecular targets. Here, we review strategies for natural product screening that harness the recent technical advances that have reduced these barriers. We also assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products, and highlight recent examples of natural products in antimicrobial drug discovery and as inhibitors of protein-protein interactions. The growing appreciation of functional assays and phenotypic screens may further contribute to a revival of interest in natural products for drug discovery.

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The re-emergence of natural products for drug discovery in the genomics era

: The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

This book succeeds Review of Medical Pharmacology , by Meyers, Jawetz, and Goldfien. Edited by B. G. Katzung, some of the important areas covered include drug receptors and pharmacodynamics, pharmacokinetics of absorption and biotransformation of drugs, autonomic pharmacology of cholinergic and adrenergic receptor stimulants and antagonists, antihypertensive agents, cardiac glycosides and other agents used in the treatment of congestive heart failure, therapeutic drugs for cardiac arrhythmias, diuretics, pharmacology of the CNS drugs such as anticonvulsants and anesthetics, antidepressants, narcotic analgesics, nonsteroidal anti-inflammatory agents, endocrine pharmacology, antimicrobial and antimycobacterial drugs, antiprotozoal and antihelmintic drugs, cancer chemotherapy, and drugs and the immune system. Written by several prominent researchers and scientists, each chapter begins with a section on the basic pharmacology, chemistry, pharmacokinetics, and pharmacodynamics of the agents under discussion. This is followed by a section on clinical pharmacology, which deals with relevant information regarding the clinical use of drugs on the various

Basic and Clinical Pharmacology

Conventional methods for carrying out carbon–hydrogen functionalization and carbon–nitrogen bond formation are typically conducted at elevated temperatures, and rely on expensive catalysts as well as the use of stoichiometric, and perhaps toxic, oxidants. In this regard, electrochemical synthesis has recently been recognized as a sustainable and scalable strategy for the construction of challenging carbon–carbon and carbon–heteroatom bonds. Here, electrosynthesis has proven to be an environmentally benign, highly effective and versatile platform for achieving a wide range of nonclassical bond disconnections via generation of radical intermediates under mild reaction conditions. This review provides an overview on the use of anodic electrochemical methods for expediting the development of carbon–hydrogen functionalization and carbon–nitrogen bond formation strategies. Emphasis is placed on methodology development and mechanistic insight and aims to provide inspiration for future synthetic applications in the field of electrosynthesis.

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Electrochemical strategies for C-H functionalization and C-N bond formation.

Microbial infectious diseases continue to be one of the leading causes of morbidity and mortality. It has been estimated that microbial species comprise about 60% of the Earth's biomass. This, together with the fact that their genetic, metabolic and physiological diversity is extraordinary, makes them a major threat to the health and development of populations across the world. Widespread antibiotic resistance, the emergence of new pathogens in addition to the resurgence of old ones, and the lack of effective new therapeutics exacerbate the problems. Thus, the need to discover and develop new antimicrobial agents is critical to improve mankind's future health. Plant secondary metabolites (PSMs) offer particular promise in this sense. Plant Kingdom could be considered a rich source of the most diverse structures (e.g. there are more than 12,000 known alkaloids, more than 8,000 phenolic compounds and over 25,000 different terpenoids), many of which were proven to possess strong antimicrobial properties (e.g. thymol, eurabienol, etc.). In many instances, PSMs can be easily isolated from the plant matrix, either in pure state or in the form of mixtures of chemically related compounds. What is also important is that the development of bacterial resistance toward natural plant products (that are generally regarded as eco-friendly) has been thus far documented in a very limited number of cases (e.g. for reserpine). Having all of the mentioned advantages of PSMs as potential antimicrobials in mind, a major question arises: why is it that there are still no commercially available or commonly used antibiotics of plant origin? This review tries to give a critical answer to this question by considering potential mechanisms of antimicrobial action of PSMs (inhibition of cell wall or protein synthesis, inducing leakage from the cells by tampering with the function of the membranes, interfering with intermediary metabolisms or DNA/RNA synthesis/function), as well as their physical and chemical properties (e.g. hydrophilicity/lipophilicity, chemical stability). To address the possible synergistic/antagonistic effects between PSMs and with standard antibiotics, special attention has been given to the antimicrobial activity of PSM-mixtures (e.g. essential oils, plant extracts). Moreover, possible ways of overcoming some of PSMs molecular limitations in respect to their usage as potential antibiotics were also discussed (e.g. derivatization that would enable fine tuning of certain molecular characteristics).

Antimicrobial Plant Metabolites: Structural Diversity and Mechanism of Action

In vitro antimicrobial activity of extracts of four Achillea species: the composition of Achillea clavennae L. (Asteraceae) extract.

The chemical composition of the aerial and root essential oils, hydrodistilled from Artemisia absinthium L. and Artemisia vulgaris L. (wild-growing populations from Serbia), were studied by gas chromatography, gas chromatography-mass spectrometry, and 13C nuclear magnetic resonance. During the storage of plant material under controlled conditions, a significant decrease of essential oil yields (isolated directly after drying and after 1 year of storage) and significant differences in their chemical compositions were observed. A possible mechanism for the observed oil component interconversion has been discussed. The noticeable differences in the chemical composition of the oils isolated from roots and aerial parts of A. absinthium and A. vulgaris were also correlated with the diverging biosynthetic pathways of volatiles in the respective plant organs. The antimicrobial activities against the common human pathogens of all of the isolated oils were tested according to National Committee on Clinical Laboratory Standards. The oils showed a broad spectrum of antimicrobial activity against the tested strains. Therefore, these oils can be used as flavor and fragrance ingredients.

Chemical composition of the essential oils of serbian wild-growing Artemisia absinthium and Artemisia vulgaris.

The volatile constituents of the sterile stems of Equisetum arvense L. (Equisetaceae) were investigated for the first time using GC, GC/MS and (13)C-NMR. Twenty-five compounds were identified. Hexahydrofarnesyl acetone (18.34%), cis-geranyl acetone (13.74%), thymol (12.09%) and trans-phytol (10.06%) were the major constituents. A disk diffusion method was used for the evaluation of the antimicrobial activity of this oil against a panel of microorganisms (bacteria: Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella enteritidis; fungi: Aspergillus niger and Candida albicans). The 1:10 dilution of the essential oil of Equisetum arvense L. was shown to possess a broad spectrum of a very strong antimicrobial activity against all tested strains.

Niko S. Radulović

Papers

Antimicrobial Plant Metabolites: Structural Diversity and Mechanism of Action

In vitro antimicrobial activity of extracts of four Achillea species: the composition of Achillea clavennae L. (Asteraceae) extract.

Chemical composition of the essential oils of serbian wild-growing Artemisia absinthium and Artemisia vulgaris.

Composition and antimicrobial activity of equisetum arvense l. essential oil

Screening of in vitro antimicrobial and antioxidant activity of nine Hypericum species from the Balkans