Chlorophylls make Earth green, are the central constituents in the engine of photosynthesis, and not surprisingly have garnered immense attention. A chlorin, the core chromophore of a chlorophyll, is ...a dihydroporphyrin macrocycle that contains one pyrroline ring and three pyrrole rings. The dominant method for the synthesis of chlorins has entailed the derivatization of porphyrins. The present review covers the ostensibly simple conversion of porphyrins, regardless of synthetic or biological origin, to chlorins. The period covered encompasses the entire history since the beginnings of chlorin synthetic chemistry in the early 20th century through 2015. Representative transformations include hydrogenation, cycloaddition, annulation, and diverse “breaking and mending” approaches. Altogether, the synthesis of >1000 chlorins or chlorin-like compounds (containing >50 distinct pyrroline motifs) is described. Such diversity animates the question “what structural features are essential for a chlorin to resemble chlorophyll?” To begin to address the structure–spectrum relationship, > 250 absorption spectra are provided for representative structures. The synthesis and spectral properties of the vast collection of compounds described herein are expected to illuminate the scope to which synthetic chlorins can serve as surrogates for chlorophylls and be exploited in diverse ways.
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The design of new molecules for photochemical studies typically requires knowledge of spectral features of pertinent chromophores beginning with the absorption spectrum (λabs) and accompanying molar ...absorption coefficient (ε, m−1 cm−1) and often extending to the fluorescence spectrum (λem) and fluorescence quantum yield (Φf), where the fluorescence properties may be of direct relevance or useful as proxies to gain insight into the nature of the first excited singlet state. PhotochemCAD databases, developed over a period of 30 years, are described here. The previous databases for 150 compounds have been expanded to encompass 339 compounds for which absorption spectra (including ε values), fluorescence spectra (including Φf values) and references to the primary literature have been included where available (552 spectra altogether). The compounds exhibit spectra in the ultraviolet, visible and/or near‐infrared spectral regions. The compound classes and number of members include acridines (21), aromatic hydrocarbons (41), arylmethane dyes (11), azo dyes (18), biomolecules (18), chlorins/bacteriochlorins (16), coumarins (14), cyanine dyes (19), dipyrrins (7), heterocycles (26), miscellaneous dyes (13), oligophenylenes (13), oligopyrroles (6), perylenes (5), phthalocyanines (11), polycyclic aromatic hydrocarbons (16), polyenes/polyynes (10), porphyrins (34), quinones (24) and xanthenes (15). A database of 31 solar spectra also is included.
The availability of absorption and fluorescence data (with ε and Φf values) is essential for for diverse studies in photochemistry including informed molecular design of photofunctional molecules. Such spectra for 339 compounds (spanning the ultraviolet, visible, and near‐infrared spectral regions) have been assembled (339 absorption, 213 fluorescence spectra) in a database that is rooted with >650 references to the original scientific literature. A small database of 31 solar spectra also is available. The databases are available for diverse photophysical and spectrometric calculations with PhotochemCAD or other programs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Steroid hormones bind receptors in the cell nucleus and in the cell membrane. The most widely studied class of steroid hormone receptors are the nuclear receptors, named for their function ...as ligand-dependent transcription factors in the cell nucleus. Nuclear receptors, such as estrogen receptor alpha, can also be anchored to the plasma membrane, where they respond to steroids by activating signaling pathways independent of their function as transcription factors. Steroids can also bind integral membrane proteins, such as the G protein–coupled estrogen receptor. Membrane estrogen and progestin receptors have been cloned and characterized in vitro and influence the development and function of many organ systems. Membrane androgen receptors were cloned and characterized in vitro, but their function as androgen receptors in vivo is unresolved. We review the identity and function of membrane proteins that bind estrogens, progestins, and androgens. We discuss evidence that membrane glucocorticoid and mineralocorticoid receptors exist, and whether glucocorticoid and mineralocorticoid nuclear receptors act at the cell membrane. In many cases, integral membrane steroid receptors act independently of nuclear steroid receptors, even though they may share a ligand.
Synthetic meso-substituted porphyrins offer significant attractions compared with naturally occurring β-substituted porphyrins. The attractions include the rectilinear arrangement of the four meso ...substituents and potential synthetic amenability from pyrrole and simple acyl reactants, thereby avoiding the cumbersome syntheses of β-substituted pyrroles. In practice, however, the classical methods for the synthesis of meso-substituted porphyrins were characterized by high-temperature reactions, limited scope of substituents, and statistical mixtures accompanied by laborious chromatography if porphyrins bearing two different types of substituents were sought. Such methods left unrealized the tremendous utility of meso-substituted porphyrins across the enormously broad field of porphyrin science, which touches pure chemistry; energy, life and materials sciences; and medicine. This Account surveys a set of strategies, developed over a generation, that provide rational access to porphyrins bearing up to four distinct meso substituents. A “2 + 2” route employs a dipyrromethane-1,9-dicarbinol and a dipyrromethane (bearing ABC- and D-substituents, respectively) in a two-step, one-flask process of acid-catalyzed condensation followed by oxidation at room temperature to form the free base “ABCD-porphyrin.” A “bilane” route relies on the acid-catalyzed reaction of a 1-acyldipyrromethane (CD substituents) and a 9-bromodipyrromethane-1-carbinol (AB substituents) to form the corresponding 19-acyl-1-bromobilane. Reaction of the latter compound in the presence of MgBr2, 1,8-diazabicyclo5.4.0undec-7-ene (DBU), and toluene at reflux exposed to air affords the corresponding magnesium(II) porphyrin. The two routes are complementary, both in scope and in implementation. A suite of methods also affords trans-A2B2-porphyrins by reaction of a dipyrromethane and an aldehyde, self-condensation of a dipyrromethane-1-carbinol, or self-condensation of a 1-acyldipyrromethane. These new routes are also useful for preparing sparsely substituted porphyrins, which bear fewer than four meso substituents (e.g., trans-AB-porphyrins, A-porphyrins). Because of their compact size and the ability to incorporate hydrophilic or amphipathic groups, such molecules are ideal for biological applications. The success of these new synthetic strategies has relied on a number of advances including (1) the development of simple yet efficient routes to dipyrromethanes, acyldipyrromethanes, and dipyrromethane-carbinols, (2) the identification of acid catalysts and reaction conditions for condensations of pyrromethane species without accompanying acidolysis (which underlies scrambling and formation of a mixture of porphyrin products), (3) the development of analytical methods to rapidly screen for scrambling and to characterize the distribution of oligopyrromethanes and macrocycles, (4) selection and refinement of synthetic methods to increase yields and to limit or avoid use of chromatography, thereby achieving scalability to multigram levels, and (5) exploitation of discoveries concerning the fundamental chemistry of pyrrolic species. With these developments, the prior era of porphyrin synthesis has been supplanted with rational routes that proceed under very mild conditions and afford a single porphyrin bearing up to four distinct meso substituents. The meso substituents encompass a very wide range of molecular complexity. The resulting porphyrins can serve as building blocks in the construction of model systems, as components of molecular materials, and as surrogates for naturally occurring tetrapyrrole macrocycles.
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic worldwide, particularly in countries that consume a Western diet, and can lead to life-threatening conditions such as cirrhosis ...and hepatocellular carcinoma. With increasing prevalence of NAFLD in both children and adults, an understanding of the factors that promote NAFLD development and progression is crucial. Environmental agents, including endocrine-disrupting chemicals (EDCs), which have been linked to other diseases, may play a role in NAFLD development. Increasing evidence supports a developmental origin of liver disease, and early-life exposure to EDCs could represent one risk factor for the development of NAFLD later in life. Rodent studies provide the strongest evidence for this link, but further studies are needed to define whether there is a causal link between early-life EDC exposure and NAFLD development in humans. Elucidating the molecular mechanisms underlying development of NAFLD in the context of developmental EDC exposures may identify biomarkers for people at risk, as well as potential intervention and/or therapeutic opportunities for the disease.
The references cited in this mini-review were selected from manuscripts found through a PubMed search, without a publication year cutoff. References found in these publications provided additional articles to search and cite.
Tolyporphins A-R constitute fundamentally distinct members of the tetrapyrrole pigments of life family. The 18 members present diversity at multiple levels including the chromophore ...(dioxobacteriochlorin, oxochlorin, porphyrin); composition of the pyrroline substituents (hydroxy, acetoxy, or one of four
C
-glycosides); and stereochemical configuration of the pyrroline substituents. Eleven of the 18 tolyporphins contain at least one
C
-glycoside; each
C
-glycoside has a β,
d
configuration and lacks a 6′-hydroxy group: 3′,6′-dideoxygalactose (common name abequose), 2′-
O
-acetyl-3′,6′-dideoxygalactose (2′-
O
-acetylabequose), 6′-deoxygalactose (
d
-fucose), or 6′-deoxygulose (antiarose). Rare are such glycosides outside of tolyporphins: (2′-
O
-acetyl)abequose is reported only in the glycan polymer attached to the cell wall of two strains of Gram-negative bacteria, and antiarose is reported in one bacterial natural product and ∼50 plant cardiac glycosides. Eight of the 18 tolyporphins are bis(
C
-glycosides), an exceptionally uncommon motif in natural products. The biosynthetic pathways to the family of tolyporphins remain unknown. Regardless of such diversity, each tolyporphin member shares a common pattern of perimeter methyl substituents that coheres with derivation from uroporphyrinogen III, the universal precursor in the established pathway to native tetrapyrroles. Here, transformations required to convert uroporphyrinogen III to all 18 tolyporphins are considered in the context of plausible biosynthetic pathways. Heme
d
1
, perhaps the closest relative (yet still a distant cousin) of tolyporphins, and for which key biosynthetic transformations remain undeciphered, provides a point of reference. Taken together, the work provides the foundation for bioinformatic searching for enzymes associated with the biosynthesis and diversification of tolyporphins.
Tolyporphins, relatively new members of the pigments of life family found in a cyanobacterium, differ in the chromophores, pyrroline substituents, and stereochemistry, yet likely all derive from uroporphyrinogen III.
Background
The stage, when tissues and organs are growing, is very vulnerable to environmental influences, but it’s not clear how exposure during this time causes changes to the epigenome and ...increases the risk of hormone-related illnesses like uterine fibroids (UFs).
Methods
Developmental reprogramming of myometrial stem cells (MMSCs), the putative origin from which UFs originate, was investigated in vitro and in the Eker rat model by RNA-seq, ChIP-seq, RRBS, gain/loss of function analysis, and luciferase activity assays.
Results
When exposed to the endocrine-disrupting chemical (EDC) diethylstilbestrol during Eker rat development, MMSCs undergo a reprogramming of their estrogen-responsive transcriptome. The reprogrammed genes in MMSCs are known as estrogen-responsive genes (ERGs) and are activated by mixed lineage leukemia protein-1 (MLL1) and DNA hypo-methylation mechanisms. Additionally, we observed a notable elevation in the expression of ERGs in MMSCs from Eker rats exposed to natural steroids after developmental exposure to EDC, thereby augmenting estrogen activity.
Conclusion
Our studies identify epigenetic mechanisms of MLL1/DNA hypo-methylation-mediated MMSC reprogramming. EDC exposure epigenetically targets MMSCs and leads to persistent changes in the expression of a subset of ERGs, imparting a hormonal imprint on the ERGs, resulting in a “hyper-estrogenic” phenotype, and increasing the hormone-dependent risk of UFs.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Cell division in bacteria is mediated by a multiprotein assembly called the divisome. A major function of this machinery is the synthesis of the peptidoglycan (PG) cell wall that caps the daughter ...poles and prevents osmotic lysis of the newborn cells. Recent studies have implicated a complex of FtsW and FtsI (FtsWI) as the essential PG synthase within the divisome; however, how PG polymerization by this synthase is regulated and coordinated with other activities within the machinery is not well understood. Previous results have implicated a conserved subcomplex of division proteins composed of FtsQ, FtsL, and FtsB (FtsQLB) in the regulation of FtsWI, but whether these proteins act directly as positive or negative regulators of the synthase has been unclear. To address this question, we purified a five-member Pseudomonas aeruginosa division complex consisting of FtsQLB-FtsWI. The PG polymerase activity of this complex was found to be greatly stimulated relative to FtsWI alone. Purification of complexes lacking individual components indicated that FtsL and FtsB are sufficient for FtsW activation. Furthermore, support for this activity being important for the cellular function of FtsQLB was provided by the identification of two division-defective variants of FtsL that still form normal FtsQLB-FtsWI complexes but fail to activate PG synthesis. Thus, our results indicate that the conserved FtsQLB complex is a direct activator of PG polymerization by the FtsWI synthase and thereby define an essential regulatory step in the process of bacterial cell division.
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Biofilm formation is a complex, ordered process. In the opportunistic pathogen Pseudomonas aeruginosa, Psl and Pel exopolysaccharides and extracellular DNA (eDNA) serve as structural components of ...the biofilm matrix. Despite intensive study, Pel's chemical structure and spatial localization within mature biofilms remain unknown. Using specialized carbohydrate chemical analyses, we unexpectedly found that Pel is a positively charged exopolysaccharide composed of partially acetylated 1→4 glycosidic linkages of N-acetylgalactosamine and N-acetylglucosamine. Guided by the knowledge of Pel's sugar composition, we developed a tool for the direct visualization of Pel in biofilms by combining Pel-specific Wisteria floribunda lectin staining with confocal microscopy. The results indicate that Pel cross-links eDNA in the biofilm stalk via ionic interactions. Our data demonstrate that the cationic charge of Pel is distinct from that of other known P. aeruginosa exopolysaccharides and is instrumental in its ability to interact with other key biofilm matrix components.
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