ssDNA is an allosteric regulator of the C. crescentus SOS-independent DNA damage response transcription activator, DriD.

DNA damage repair systems are critical for genomic integrity. However, they must be coordinated with DNA replication and cell division to ensure accurate genomic transmission. In most bacteria, this coordination is mediated by the SOS response through LexA, which triggers a halt in cell division until repair is completed. Recently, an SOS-independent damage response system was revealed in Caulobacter crescentus. This pathway is controlled by the transcription activator, DriD, but how DriD senses and signals DNA damage is unknown. To address this question, we performed biochemical, cellular, and structural studies. We show that DriD binds a specific promoter DNA site via its N-terminal HTH domain to activate transcription of genes, including the cell division inhibitor didA A structure of the C-terminal portion of DriD revealed a WYL motif domain linked to a WCX dimerization domain. Strikingly, we found that DriD binds ssDNA between the WYL and WCX domains. Comparison of apo and ssDNA-bound DriD structures reveals that ssDNA binding orders and orients the DriD domains, indicating a mechanism for ssDNA-mediated operator DNA binding activation. Biochemical and in vivo studies support the structural model. Our data thus reveal the molecular mechanism underpinning an SOS-independent DNA damage repair pathway.

Decarboxylative Sulfinylation Enables a Direct, Metal-Free Access to Sulfoxides from Carboxylic Acids.

The intermediate oxidation state of sulfoxides is central to the plethora of their applications in chemistry and medicine, yet it presents challenges for an efficient synthetic access, limiting the structural diversity of currently available sulfoxides. Here, we report a data-guided development of direct decarboxylative sulfinylation that enables the previously inaccessible functional group interconversion of carboxylic acids to sulfoxides in a reaction with sulfinates. Given the broad availability of carboxylic acids and the growing synthetic potential of sulfinates, the direct decarboxylative sulfinylation is poised to improve the structural diversity of synthetically accessible sulfoxides. The reaction is facilitated by a kinetically favored sulfoxide formation from the intermediate sulfinyl sulfones, despite the strong thermodynamic preference for the sulfone formation, unveiling the previously unknown and chemoselective radicalophilic sulfinyl sulfone reactivity.

Bond Memory in Dynamically Determined Stereoselectivity.

The carboborative ring contraction of cyclohexenes exhibits an abnormal selectivity pattern in which a formally concerted double migration gives rise to predominant but not exclusive inversion products. In dynamic trajectories, the inversion and retention products are formed from the same transition state, and the trajectories accurately account for the experimental product ratios. The unusual origin of the selectivity is the dynamically retained non-equivalence of newly formed versus pre-existing bonds after the first bond migration.

Visible Light-Induced Borylation of C-O, C-N, and C-X Bonds.

Boronic acids are centrally important functional motifs and synthetic precursors. Visible light-induced borylation may provide access to structurally diverse boronates, but a broadly efficient photocatalytic borylation method that can effect borylation of a wide range of substrates, including strong C-O bonds, remains elusive. Herein, we report a general, metal-free visible light-induced photocatalytic borylation platform that enables borylation of electron-rich derivatives of phenols and anilines, chloroarenes, as well as other haloarenes. The reaction exhibits excellent functional group tolerance, as demonstrated by the borylation of a range of structurally complex substrates. Remarkably, the reaction is catalyzed by phenothiazine, a simple organic photocatalyst with MW < 200 that mediates the previously unachievable visible light-induced single electron reduction of phenol derivatives with reduction potentials as negative as approximately - 3 V versus SCE by a proton-coupled electron transfer mechanism. Mechanistic studies point to the crucial role of the photocatalyst-base interaction.

Visible-Light-Enabled Direct Decarboxylative N-Alkylation.

The development of efficient and selective C-N bond-forming reactions from abundant feedstock chemicals remains a central theme in organic chemistry owing to the key roles of amines in synthesis, drug discovery, and materials science. Herein, we present a dual catalytic system for the N-alkylation of diverse aromatic carbocyclic and heterocyclic amines directly with carboxylic acids, by-passing their preactivation as redox-active esters. The reaction, which is enabled by visible-light-driven, acridine-catalyzed decarboxylation, provides access to N-alkylated secondary and tertiary anilines and N-heterocycles. Additional examples, including double alkylation, the installation of metabolically robust deuterated methyl groups, and tandem ring formation, further demonstrate the potential of the direct decarboxylative alkylation (DDA) reaction.

Highly Stereoselective and Catalytic Desulfitative C-O and C-I Dienylation with Sulfolenes: the Importance of Basic Additives.

Conjugated dienes and polyenes are central structural motifs of natural products, and key synthetic intermediates in organic synthesis and materials science. We describe herein a palladium-catalyzed dienylation of aryl, heteroaryl, and vinyl triflates, nonaflates and iodides that were previously identified as recalcitrant substrates for the sulfolene-mediated catalytic dienylation. The method has now been successfully expanded to C-O and C-I dienylation, demonstrating broad scope with respect to sulfonates, iodides and sulfolenes. The reactions proceed with high regio- and stereoselectivity, and efficiency that are strongly influenced by basic additives, whose influence on the reaction performance was systematically studied.

Organoboron chemistry comes to light: recent advances in photoinduced synthetic approaches to organoboron compounds.

Photoinduced synthetic approaches to organoboron compounds have attracted significant attention in the recent years. Photochemical activation of organic molecules enables generation of reactive intermediates from a variety of precursors, resulting in borylation methods with improved and broader substrate scopes. The review summarizes recent developments in the area of photoinduced reactions of organoboron compounds with an emphasis on borylation of haloarenes, amine derivatives, and redox-active esters of carboxylic acids, as well as photoinduced rearrangements of organoboron compounds and photoinduced synthesis of organoboron compounds from alkenes and alkynes.

Highly Regio- and Stereoselective Catalytic Synthesis of Conjugated Dienes and Polyenes.

Conjugated dienes and polyenes are typically synthesized by sequential introduction of C═C bonds. Here, we report a practical and scalable, catalytic dienylation that is highly regio- and stereoselective for both C═C bonds. The reaction is enabled by a stereoselective palladium-catalyzed cross-coupling that is preceded by a regioselective base-induced ring opening of readily available sulfolenes. The dienylation reaction is particularly useful for the synthesis of synthetically challenging dienes containing cis double bonds. We also show that the reaction can serve as a synthetic platform for the construction of conjugated polyenes.

Efficient synthesis of 3-sulfolenes from allylic alcohols and 1,3-dienes enabled by sodium metabisulfite as a sulfur dioxide equivalent.

We present herein an efficient and practical method for a gram scale synthesis of 3-sulfolenes using sodium metabisulfite as a safe, inexpensive, and easy to handle sulfur dioxide equivalent. Diversely-substituted 3-sulfolenes can be prepared by reacting a variety of 1,3-dienes or allylic alcohols with sodium metabisulfite in aqueous hexafluoroisopropanol (HFIP) or in aqueous methanol in the presence of potassium hydrogen sulfate. Advantageously, the method enables conversion of allylic alcohols directly to 3-sulfolenes, bypassing intermediate 1,3-dienes.

Demystifying Orbital Emergencies: A Pictorial Review.

Imaging of the orbit plays an important role in the workup of orbital emergencies. Orbital imaging is particularly useful in the emergency department, where clinical history and physical examination may be limited or delayed until the exclusion or treatment of more life-threatening conditions. Cross-sectional orbital imaging with multidetector computed tomography (CT) and magnetic resonance (MR) imaging is commonly performed in addition to ultrasonography. In an emergent setting, CT is the preferred modality when evaluating for intraorbital foreign bodies, fractures, or calcifications within a mass lesion. MR imaging is typically the modality of choice for orbital pathologic conditions, owing to its superior ability to delineate the orbital soft tissues and visual pathways. CT and MR imaging together may supplement clinical evaluation by helping establish an accurate diagnosis, providing an objective assessment of disease extent and progression, and assisting in pretreatment planning. Orbital emergencies have a spectrum of cross-sectional imaging findings in four major categories: infection, trauma, vascular disease, and inflammation. Use of a systematic approach to these entities will assist the radiologist with identifying immediate threats to vision and thereby facilitate prompt clinical management. Familiarity with the clinical presentations also improves the radiologist's diagnostic confidence and role in guiding patient care. This article reviews imaging protocols, relevant orbital anatomy, the role of CT and MR imaging, and key imaging findings of orbital emergencies that the radiologist must know. © RSNA, 2017.

Multimodal Acridine Photocatalysis Enables Direct Access to Thiols from Carboxylic Acids and Elemental Sulfur.

Development of photocatalytic systems that facilitate mechanistically divergent steps in complex catalytic manifolds by distinct activation modes can enable previously inaccessible synthetic transformations. However, multimodal photocatalytic systems remain understudied, impeding their implementation in catalytic methodology. We report herein a photocatalytic access to thiols that directly merges the structural diversity of carboxylic acids with the ready availability of elemental sulfur without substrate preactivation. The photocatalytic transformation provides a direct radical-mediated segue to one of the most biologically important and synthetically versatile organosulfur functionalities, whose synthetic accessibility remains largely dominated by two-electron-mediated processes based on toxic and uneconomical reagents and precursors. The two-phase radical process is facilitated by a multimodal catalytic reactivity of acridine photocatalysis that enables both the singlet excited state PCET-mediated decarboxylative carbon-sulfur bond formation and the previously unknown radical reductive disulfur bond cleavage by a photoinduced HAT process in the silane-triplet acridine system. The study points to a significant potential of multimodal photocatalytic systems in providing unexplored directions to previously inaccessible transformations.

Decarboxylative Triazolation Enables Direct Construction of Triazoles from Carboxylic Acids.

Triazoles have major roles in chemistry, medicine, and materials science, as centrally important heterocyclic motifs and bioisosteric replacements for amides, carboxylic acids, and other carbonyl groups, as well as some of the most widely used linkers in click chemistry. Yet, the chemical space and molecular diversity of triazoles remains limited by the accessibility of synthetically challenging organoazides, thereby requiring preinstallation of the azide precursors and restricting triazole applications. We report herein a photocatalytic, tricomponent decarboxylative triazolation reaction that for the first time enables direct conversion of carboxylic acids to triazoles in a single-step, triple catalytic coupling with alkynes and a simple azide reagent. Data-guided inquiry of the accessible chemical space of decarboxylative triazolation indicates that the transformation can improve access to the structural diversity and molecular complexity of triazoles. Experimental studies demonstrate a broad scope of the synthetic method that includes a variety of carboxylic acid, polymer, and peptide substrates. When performed in the absence of alkynes, the reaction can also be used to access organoazides, thereby obviating preactivation and specialized azide reagents and providing a two-pronged approach to C-N bond-forming decarboxylative functional group interconversions.

Catalytic Dienylation: An Emergent Strategy for the Stereoselective Construction of Conjugated Dienes and Polyenes.

Stereoselective construction of conjugated dienes and polyenes has remained an enduring synthetic problem, due to the central roles they play in natural product synthesis, methodology, and medicine. This review focuses on the recent developments in dienylation as an emerging strategy for the direct installation of unsaturated four carbon atom units of conjugated π-systems, outlining the regio- and stereoselectivity, as well as the synthetic scope of reactions with various dienylating reagents and the mechanistic implications of the catalytic cross-coupling processes that are used to enable dienylation.

Tricomponent Decarboxysulfonylative Cross-Coupling Facilitates Direct Construction of Aryl Sulfones and Reveals a Mechanistic Dualism in the Acridine/Copper Photocatalytic System.

Dual catalytic systems involving photocatalytic activation and transition metal-catalyzed steps have enabled innovative approaches to the construction of carbon-carbon and carbon-heteroatom bonds. However, the mechanistic complexity of the dual catalytic processes presents multiple challenges for understanding of the roles of divergent catalytic species that can impede the development of future synthetic methods. Here, we report a dual catalytic process that enables the previously inaccessible, broad-scope, direct conversion of carboxylic acids to aromatic sulfones-centrally important carbonyl group bioisosteric replacements and synthetic intermediates-by a tricomponent decarboxysulfonylative cross-coupling with aryl halides. Detailed mechanistic and computational studies revealed the roles of the copper catalyst, base, and halide anions in channeling the acridine/copper system via a distinct dual catalytic manifold. In contrast to the halide-free decarboxylative conjugate addition that involves cooperative dual catalysis via low-valent copper species, the halide counteranions divert the decarboxysulfonylative cross-coupling with aryl halides through a two-phase, orthogonal relay catalytic manifold, comprising a kinetically coupled (via antithetical inhibitory and activating roles of the base in the two catalytic cycles), mechanistically discrete sequence of a photoinduced, acridine-catalyzed decarboxylative process and a thermal copper-catalyzed arylative coupling. The study underscores the importance of non-innocent roles of counteranions and key redox steps at the interface of catalytic cycles for enabling previously inaccessible dual catalytic transformations.

Functional group divergence and the structural basis of acridine photocatalysis revealed by direct decarboxysulfonylation.

The reactivity of the sulfonyl group varies dramatically from nucleophilic sulfinates through chemically robust sulfones to electrophilic sulfonyl halides-a feature that has been used extensively in medicinal chemistry, synthesis, and materials science, especially as bioisosteric replacements and structural analogs of carboxylic acids and other carbonyls. Despite the great synthetic potential of the carboxylic to sulfonyl functional group interconversions, a method that can convert carboxylic acids directly to sulfones, sulfinates and sulfonyl halides has remained out of reach. We report herein the development of a photocatalytic system that for the first time enables direct decarboxylative conversion of carboxylic acids to sulfones and sulfinates, as well as sulfonyl chlorides and fluorides in one step and in a multicomponent fashion. A mechanistic study prompted by the development of the new method revealed the key structural features of the acridine photocatalysts that facilitate the decarboxylative transformations and provided an informative and predictive multivariate linear regression model that quantitatively relates the structural features with the photocatalytic activity.

Applications of hyperspectral imaging in plant phenotyping.

Our ability to interrogate and manipulate the genome far exceeds our capacity to measure the effects of genetic changes on plant traits. Much effort has been made recently by the plant science research community to address this imbalance. The responses of plants to environmental conditions can now be defined using a variety of imaging approaches. Hyperspectral imaging (HSI) has emerged as a promising approach to measure traits using a wide range of wavebands simultaneously in 3D to capture information in lab, glasshouse, or field settings. HSI has been applied to define abiotic, biotic, and quality traits for optimisation of crop management.

Molecular dissection of the glutamine synthetase-GlnR nitrogen regulatory circuitry in Gram-positive bacteria.

How bacteria sense and respond to nitrogen levels are central questions in microbial physiology. In Gram-positive bacteria, nitrogen homeostasis is controlled by an operon encoding glutamine synthetase (GS), a dodecameric machine that assimilates ammonium into glutamine, and the GlnR repressor. GlnR detects nitrogen excess indirectly by binding glutamine-feedback-inhibited-GS (FBI-GS), which activates its transcription-repression function. The molecular mechanisms behind this regulatory circuitry, however, are unknown. Here we describe biochemical and structural analyses of GS and FBI-GS-GlnR complexes from pathogenic and non-pathogenic Gram-positive bacteria. The structures show FBI-GS binds the GlnR C-terminal domain within its active-site cavity, juxtaposing two GlnR monomers to form a DNA-binding-competent GlnR dimer. The FBI-GS-GlnR interaction stabilizes the inactive GS conformation. Strikingly, this interaction also favors a remarkable dodecamer to tetradecamer transition in some GS, breaking the paradigm that all bacterial GS are dodecamers. These data thus unveil unique structural mechanisms of transcription and enzymatic regulation.

Photoinduced C(sp3)-H sulfination empowers the direct and chemoselective introduction of the sulfonyl group.

Direct installation of the sulfinate group by the functionalization of unreactive aliphatic C-H bonds can provide access to most classes of organosulfur compounds, because of the central position of sulfinates as sulfonyl group linchpins. Despite the importance of the sulfonyl group in synthesis, medicine, and materials science, a direct C(sp3)-H sulfination reaction that can convert abundant aliphatic C-H bonds to sulfinates has remained elusive, due to the reactivity of sulfinates that are incompatible with typical oxidation-driven C-H functionalization approaches. We report herein a photoinduced C(sp3)-H sulfination reaction that is mediated by sodium metabisulfite and enables access to a variety of sulfinates. The reaction proceeds with high chemoselectivity and moderate to good regioselectivity, affording only monosulfination products and can be used for a solvent-controlled regiodivergent distal C(sp3)-H functionalization.

Z-Selective Dienylation Enables Stereodivergent Construction of Dienes and Unravels a Ligand-Driven Mechanistic Dichotomy.

Development of stereoselective and efficient reactions for construction of conjugated dienes and polyenes has remained at the forefront of organic chemistry, due to their key roles in medicinal chemistry, organic synthesis, and materials science. The synthesis of conjugated dienes and polyenes is typically accomplished in a multistep manner by sequential installation of individual C=C bonds because it allows for control of stereoselectivity and efficiency of formation of each double bond. A conceptually distinct dienylation approach entails a stereoselective appendage of a four-carbon unit, shortcutting diene synthesis. Dienylation with sulfolene provided a direct route to E-dienes, but the synthesis of substantially more challenging Z-dienes remained elusive. Here, we report that a highly Z-selective dienylation can be now achieved by a simple adjustment of a ligand, enabling stereodivergent synthesis of E- and Z-dienes from one reagent and in one step. A detailed mechanistic investigation of the E- and Z-selective dienylation provided insight into the divergent behavior of the two catalytic systems and revealed that differences in relative stabilities of catalytically active palladium phosphine complexes have a major impact on the stereochemical outcomes of the dienylation.

Photocatalytic decarboxylative amidosulfonation enables direct transformation of carboxylic acids to sulfonamides.

Sulfonamides feature prominently in organic synthesis, materials science and medicinal chemistry, where they play important roles as bioisosteric replacements of carboxylic acids and other carbonyls. Yet, a general synthetic platform for the direct conversion of carboxylic acids to a range of functionalized sulfonamides has remained elusive. Herein, we present a visible light-induced, dual catalytic platform that for the first time allows for a one-step access to sulfonamides and sulfonyl azides directly from carboxylic acids. The broad scope of the direct decarboxylative amidosulfonation (DDAS) platform is enabled by the efficient direct conversion of carboxylic acids to sulfinic acids that is catalyzed by acridine photocatalysts and interfaced with copper-catalyzed sulfur-nitrogen bond-forming cross-couplings with both electrophilic and nucleophilic reagents.