Photocycloaddition Reactions Research Articles

Enabling High Structural Specificity to Lipidomics by Coupling Photochemical Derivatization with Tandem Mass Spectrometry.

Lipids have pivotal roles in many biological processes, including energy storage, signal transduction, and plasma membrane formation. A disruption of lipid homeostasis is found to be associated with a range of diseases, such as cardiovascular diseases, diabetes, and cancer. Fundamental lipid biology and disease diagnostics can benefit from monitoring lipid changes in cells, tissues, organs, or the whole biological system. Therefore, it is important to develop lipid analysis tools to achieve comprehensive lipid characterization and quantitation. Over the past two decades, mass spectrometry (MS) has become the method of choice for qualitative and quantitative analyses of lipids, owing to its high sensitivity, multiplexed analysis, and soft ionization features. With the rapid development and adoption of ultrahigh-resolution MS, isobaric lipids can now be routinely resolved. By contrast, the structural characterization and quantitation of isomeric lipids remain an analytical challenge. Although some lipid C═C location or sn-isomers can be resolved by chromatography, ion mobility, or selective ionization approaches, a detailed structural characterization on the lipidome-wide level needs to be achieved.Over the past six years, we have successfully combined the Paternò-Büchi (PB) reaction, which is a UV-promoted photocycloaddition reaction specific to the C═C, with tandem MS (MS/MS) to locate the C═C in lipids and quantify lipid C═C location isomers. The PB reactions have analytical advantages such as a simple experimental setup, rapid lipid C═C derivatization, and highly specific C═C cleavage during PB-MS/MS to produce abundant diagnostic ions. More importantly, without a need of isomer separation or a comparison to authentic standards, PB-MS/MS can be directly applied to identify and quantify a mixture of lipid C═C location isomers, often coexisting with molar ratios sensitive to the biological state of the system. The PB-MS/MS method is compatible with conventional shotgun lipidomics employing a nanoelectrospray ionization or a large-sale lipid structural analysis via liquid chromatography (LC) coupled to any mass spectrometer with tandem MS capability. The PB-MS/MS method is highly versatile, as a variety of PB reagents can be tailored to a broad range of applications. Besides UV-promoted PB reactions, visible-light PB reactions have also been developed to offer more flexibility for a lipid analysis. By using selected PB reagents, the sn-positions of fatty acyls can be resolved together with C═C locations in phospholipids. This method has been used in lipidomic analyses of tissue, blood, and plasma from animal models and clinical samples, demonstrating the potential of using lipid C═C or sn-location isomer ratios for phenotyping and disease diagnostics. Lipid isomer-resolving MS imagings of tissues and single-cell lipid analysis have also been demonstrated by a proper implementation of PB-MS/MS.

Photocycloadditions of Arenes Derived from Lignin.

Intramolecular photocycloaddition reactions of 3,4-alkoxybenzonitriles derived from vanillin with alkenes have been investigated. In contrast to previous reports on photochemical reactions with these compounds, mainly [2 + 3] cycloaddition has been observed. A competing [2 + 2] photocycloaddition plays a minor role. Most probably, these additions occur at the singlet state S1. In the case of a triplet reaction, a different regioselectivity of the [2 + 2] cycloaddition would be observed. Linear and angular [2 + 3] cycloadducts are formed as major products. The first isomer is transformed in the second one by a photochemical vinyl-cyclopropane rearrangement, which increases the selectivity of the reaction. The influence of the substitution pattern on the reactivity and the selectivity has also been investigated.

Water: An underappreciated reaction medium for photodimerizations

Organic solvents have been the sought-after medium to achieve light initiated transformations in laboratories and industries. Given the current emphasis on green chemistry and rising awareness of environmental pollution it may be necessary for us to utilize abundantly freely available, non-toxic and environmentally friendly water as the medium to perform photoreactions. Although water has attracted the attention of organic synthetic chemists, it is yet to receive the indispensable attention of photochemists. In this article we present examples of photocycloaddition reactions of four molecules namely coumarin, indene, cinnamic acid and acenaphthylene that are sparingly soluble in water. Photodimerization of these molecules in water is much faster and occurs at much lower concentrations than in organic solvents. Aggregation probably forced by hydrophobic association is suggested to be the cause for the increased reactivity even at lower concentrations. The dimer distribution in water is different from that in organic solvents. Further work is required to fully understand the mechanism of photodimerization in water. Although the poor solubility of organic molecules in water requires one to irradiate large volumes to collect enough useful amounts, availability of flow reactors and LEDs as light sources should help one overcome the challenges.

Solid-state [2+2] Photocycloaddition Reaction of Zinc(II) Complex Based on Quaternized 1,2-Bis(4′-pyridyl)ethylene

Solid-state [2+2] Photocycloaddition Reaction of Zinc(II) Complex Based on Quaternized 1,2-Bis(4′-pyridyl)ethylene

Ultrafast Photoclick Reaction for Selective 18F-Positron Emission Tomography Tracer Synthesis in Flow.

The development of very fast, clean, and selective methods for indirect labeling in PET tracer synthesis is an ongoing challenge. Here we present the development of an ultrafast photoclick method for the synthesis of short-lived 18F-PET tracers based on the photocycloaddition reaction of 9,10-phenanthrenequinones with electron-rich alkenes. The respective precursors are synthetically easily accessible and can be functionalized with various target groups. Using a flow photo-microreactor, the photoclick reaction can be performed in 60 s, and clinically relevant tracers for prostate cancer and bacterial infection imaging were prepared to demonstrate practicality of the method.

Nanocrystal photocatalysts trigger stereoselective photocycloaddition

Stereoselective [2 + 2] photocycloaddition provides a desirable synthetic route for target cyclobutane compounds yet remains challenging. In this issue of Chem Catalysis , Weiss and coworkers diligently apply CdSe quantum dots to photocycloaddition reactions and gain nearly quantitative yields of syn -aryl-conjugated vinylcyclobutanes. Stereoselective [2 + 2] photocycloaddition provides a desirable synthetic route for target cyclobutane compounds yet remains challenging. In this issue of Chem Catalysis , Weiss and coworkers diligently apply CdSe quantum dots to photocycloaddition reactions and gain nearly quantitative yields of syn -aryl-conjugated vinylcyclobutanes.

Construction of 2D Interdigitated Polyrotaxane Layers and their Transformation to a 3D Polyrotaxane by a Photocycloaddition Reaction between Wheels.

Following the pioneering work of Sauvage and Stoddart on rotaxanes, construction of higher dimensional polyrotaxanes in metal-organic frameworks (MOFs) via a modified protocol is challenging. We present the formation of a two-dimensional (2D) polyrotaxane and its conversion to a three-dimensional (3D) polyrotaxane MOF via a photoreaction between interdigitated "olefin wheels". For this purpose, a 2-fold entangled 2D MOF [Pb2(bpp)(sdc)2] (1), showing a 2D + 2D → 2D polyrotaxane motif, has been synthesized from the solvothermal reaction of lead(II) nitrate, 3,3'-stilbenedicarboxylic acid (H2sdc) containing an olefin group, and 1,4-bis(4-pyridyl)piperazine (bpp). The single-crystal X-ray diffraction analysis of 1 revealed that the adjacent entangled 2D layers are interdigitated, with the separation of 3.72 Å between C═C bond pairs in adjacent layers satisfying Schmidt's criteria for the occurrence of a [2 + 2] photocycloaddition reaction. Irradiation of the single crystals of 1 under UV light resulted in formation of a 3D polyrotaxane, [Pb2(bpp)(rctt-tccb)]n (2), due to a [2 + 2] photocycloaddition reaction between two wheels via a single-crystal to single-crystal transformation. The photocycloaddition and partial thermal cleavage reaction between 1 and 2 were confirmed by 1H NMR and powder X-ray diffraction (PXRD) in solution and the solid state, respectively. The present approach could contribute to the understanding of the construction of higher dimensional polyrotaxanes which are not accessible by the traditional routes.

Multifunctional Properties of a Zn(II) Coordination Complex

Metal complexes exhibiting multifunctional properties are very rare. Here, we report a Zn(II) complex, [Zn(benzoate)(25F-spy)2], where 25F-spy = 2′,5′-difluoro-4-styrylpyridine, displays unpredicted photosalient behavior while it undergoes a [2 + 2] cycloaddition reaction and exhibits unusual thermal expansion with occasional jumping, second-harmonic generation (SHG), and two-photon photoluminescence (2PPL). In the solid state, the 25F-spy ligands are packed in a head-to-tail manner. The distance between the pairs of olefin bonds, 4.279(2) Å, is not suitable for undergoing a [2 + 2] photocycloaddition reaction. However, these crystals not only undergo photodimerization quantitatively but also exhibit a photosalient effect under UV light. An interesting anisotropic thermal expansion facilitates the crystals to jump occasionally when they are heated to 140 °C, similarly to the thermosalient effect. Thermal expansion values along X1, X2, and X3 are −54.46, 106.42, and 151.69 × 10–6 K–1, respectively, with V = 204.26 × 10–6 K–1 (30–140 °C). Furthermore, these crystals exhibit light-frequency upconversion via both SHG and 2PPL. Altogether, a single crystal shows all of these diverse solid-state properties.

Photoprocesses in bis(15-crown-5)-1,3-distyrylbenzene and its complexes with metal perchlorates

Photoprocesses in bis(15-crown-5)-1,3-distyrylbenzene (DSB) and its complexes with barium and lead perchloatewere studied in MeCN by absorption, luminescence, and laser kinetic spectroscopy. The triplet DSB molecules are involved in the degradation of electronic excitation energy, together with fluorescence processes. The most efficient intersystem crossing accompanied by a decrease in the DSB fluorescence quantum yield, occurs for the lead perchlorate complex. Using quantum chemistry methods (DFT and TDDFT), the geometry, structure, and transition energies to the S1 state were calculated for trans- and cis-isomers of DSB in the gas phase and with allowance for the solvent and for 1:1 and 2:2 DSB complexes with barium cation in the ground and excited states. The orbital structures of the 2:2 complexes were calculated by ab initio method, and conclusions were drawn about the possibility of [2 + 2]- photocycloaddition reaction.

Dysprosium Coordination Polymer Incorporating Dianthracene: Thermo‐induced Phase Transition Accompanied with Magnetic and Optical Changes

AbstractDianthracene ligands obtained through photocycloaddition reaction can undergo de‐dimerization upon heating. Here we report the first examples of lanthanide‐dianthracene coordination polymers with chain structures, namely, [LnL(depma2)]Br ⋅ xH2O [1‐Ln, Ln=Dy (x=5), Gd (x=4); H2L=N1,N3‐bis(salicylideneimino)diethylenetriamine, depma2=photodimerized 9‐diethylphosphonomethylanthracene]. The lanthanide ions possess pseudo‐D5h geometries with five equatorial positions occupied by three N and two O atoms from L2− and two axial positions by the phosphonate oxygen atoms from bridging depma2 ligands. Thermo‐induced structural transformation is observed for both compounds between 120 and 140 °C, which involves de‐dimerization of depma2 and elimination of bromoethane. The structural transformation is accompanied with the switch‐on of photoluminescence and, in the case of 1‐Dy, also changes of magnetic dynamics.

Activation of 2-Cyclohexenone by BF3 Coordination: Mechanistic Insights from Theory and Experiment.

Lewis acids have recently been recognized as catalysts enabling enantioselective photochemical transformations. Mechanistic studies on these systems are however rare, either due to their absorption at wavelengths shorter than 260 nm, or due to the limitations of theoretical dynamic studies for larger complexes. In this work, we overcome these challenges and employ sub‐30‐fs transient absorption in the UV, in combination with a highly accurate theoretical treatment on the XMS‐CASPT2 level. We investigate 2‐cyclohexenone and its complex to boron trifluoride and analyze the observed dynamics based on trajectory calculations including non‐adiabatic coupling and intersystem crossing. This approach explains all ultrafast decay pathways observed in the complex. We show that the Lewis acid remains attached to the substrate in the triplet state, which in turn explains why chiral boron‐based Lewis acids induce a high enantioselectivity in photocycloaddition reactions.

Activation of 2‐Cyclohexenone by BF3 Coordination: Mechanistic Insights from Theory and Experiment

AbstractLewis acids have recently been recognized as catalysts enabling enantioselective photochemical transformations. Mechanistic studies on these systems are however rare, either due to their absorption at wavelengths shorter than 260 nm, or due to the limitations of theoretical dynamic studies for larger complexes. In this work, we overcome these challenges and employ sub‐30‐fs transient absorption in the UV, in combination with a highly accurate theoretical treatment on the XMS‐CASPT2 level. We investigate 2‐cyclohexenone and its complex to boron trifluoride and analyze the observed dynamics based on trajectory calculations including non‐adiabatic coupling and intersystem crossing. This approach explains all ultrafast decay pathways observed in the complex. We show that the Lewis acid remains attached to the substrate in the triplet state, which in turn explains why chiral boron‐based Lewis acids induce a high enantioselectivity in photocycloaddition reactions.

Advances in the synthesis of three-dimensional molecular architectures by dearomatizing photocycloadditions

The dearomatizing photocycloaddition reaction is a powerful and effective strategy for synthesizing complex, three-dimensional, polycyclic scaffolds from simple aromatic precursors. Generally, the dearomatizing photocycloaddition reaction is promoted by visible light and occurs via an energy transfer (EnT) process. This mini-review provides an overview of recent advances in this area (2018–2020), encompassing both intramolecular and intermolecular transformations. While the majority of the studies are centered on intramolecular processes due to their predictable regio- and stereo-selectivity, intermolecular transformations that show an exceptionally broad substrate scope are beginning to emerge.

Intermolecular Crossed [2 + 2] Cycloaddition Promoted by Visible-Light Triplet Photosensitization: Expedient Access to Polysubstituted 2-Oxaspiro[3.3]heptanes.

This paper describes an intermolecular cross-selective [2 + 2] photocycloaddition reaction of exocyclic arylidene oxetanes, azetidines, and cyclobutanes with simple electron-deficient alkenes. The reaction takes place under mild conditions using a commercially available Ir(III) photosensitizer upon blue light irradiation. This transformation provides access to a range of polysubstituted 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, and spiro[3.3]heptane motifs, which are of prime interest in medicinal chemistry as gem-dimethyl and carbonyl bioisosteres. A variety of further transformations of the initial cycloadducts are demonstrated to highlight the versatility of the products and enable selective access to either of a syn- or an anti-diastereoisomer through kinetic or thermodynamic epimerization, respectively. Mechanistic experiments and DFT calculations suggest that this reaction proceeds through a sensitized energy transfer pathway.

Single-crystal to single-crystal transformation of a coordination chain to a two-dimensional coordination network through a photocycloaddition reaction

UV irradiation of a unique ladder-like coordination polymer affords a two-dimensional coordination network through single-crystal to single-crystal photocycloaddition reaction.

Structural Transformations in Crystals Induced by Radiation and Pressure. Part 10. The Crystallographic Picture of Photochemical Behaviour of bi(anthracene-9,10-dimethylene) under High Pressure

The results of the monitoring of the [4 + 4] photocycloaddition reaction path in single crystals of bi(anthracene-9,10-dimethylene) at high pressure are presented. The crystal structures for several steps of the phototransformation at 0.3 GPa and 1.0 GPa were determined and analysed. The applied high pressure did not halt the photochemical reaction and almost 100% of the product molecules were obtained, although the reaction was very slowly reversible similarly to that of ambient conditions. During the crystal phototransformation the intramolecular geometry, molecular orientation and intermolecular interactions of the reactant changed more and more towards the values observed for the product. The initial increase in the unit cell volume brought about by the photochemical reaction was diminished by high pressure. High pressure itself did not significantly influence the intramolecular geometry of the reactant and product molecules, but it influenced the intermolecular interactions.

Functionalization of [60]Fullerene through photochemical reaction for fulleropyrrolidine nanovectors synthesis: Experimental and theoretical approaches

To develop novel carbon-based nanocarriers, we proposed grafting on the [60]Fullerene (C60) biologically active molecules. In this process, the formed derivatives described another approach to use photo-cycloaddition reactions for developing the third nanovector generation. As a result, the photoexcitation of C60 and azomethine ylide (AZMYtrp), with visible light, was considered as the most promising pathway to synthesize fulleropyrrolidine (FPL). After complexation with sodium cation (Na+), the error masses of FPL mono-, bis- and tris-adducts were remarkably decreased to -85.93 %, -53.99 % and -99.42 %, respectively. The formed FPL-Na+ complexes presented a significant capacity for trapping OH and OOH free radicals. In fact, their antiradical properties increased when Na+ was bonded with FPL-Na+ mono-adduct carbonyl oxygens. Comparing FPL bis-adducts regioisomers, under three different AZMYtrp forms, the neutral and anionic-neutral forms of FPL cis1 isomer were considered as the most reactive bis-nanocarriers with mole fractions of about 61 % and 46 %, respectively, in contrast to FPL-Na+, when the mixture was dominated by the anionic-neutral form of cis2 isomer with 50.34 %.

Construction of spiropyrans via [4+2] photocycloaddition reactions and its computational investigation

[4+2]-Photochemical cycloaddition provides one of the most efficient and versatile route for the exploring of carbocyclic and heterocyclic frameworks of different sizes with high atom economy. [4+2] photocycloaddition of the chalcones (2a-h) obtained by Knoevenagel condensation of thiosatin and different heteroaryl ketones viz. 2-acetyl, 3-acetyl, 4-acetylpyridines and 2-acetylthiophene olefinic 2-chloropropene with as dienophiles led to the construction of six membered novel spiropyran heterocycles (3a-h) with 60% yield. The mechanism of the [4+2] photocycloaddition reaction has been investigated in detail by DFT-B3LYP/6-31-G+ (2d, 2p) computational method.

Long-range ordered and atomic-scale control of graphene hybridization by photocycloaddition.

Chemical reactions that convert sp2 to sp3 hybridization have been demonstrated to be a fascinating yet challenging route to functionalize graphene. So far it has not been possible to precisely control the reaction sites nor their lateral order at the atomic/molecular scale. The application prospects have been limited for reactions that require long soaking, heating, electric pulses or probe-tip press. Here we demonstrate a spatially selective photocycloaddition reaction of a two-dimensional molecular network with defect-free basal plane of single-layer graphene. Directly visualized at the submolecular level, the cycloaddition is triggered by ultraviolet irradiation in ultrahigh vacuum, requiring no aid of the graphene Moiré pattern. The reaction involves both [2+2] and [2+4] cycloadditions, with the reaction sites aligned into a two-dimensional extended and well-ordered array, inducing a bandgap for the reacted graphene layer. This work provides a solid base for designing and engineering graphene-based optoelectronic and microelectronic devices.

Visible light mediated photocatalytic [2\u2009+\u20092] cycloaddition/ring-opening rearomatization cascade of electron-deficient azaarenes and vinylarenes

The broad presence of azaarene moieties in natural products has promoted the development of new functionalization reactions, giving access to larger libraries of bioactive compounds. The light promoted [2 + 2] photocycloaddition reaction to generate cyclobutanes has been extensively studied in photochemistry. In particular, De Mayo reported the [2 + 2] cycloaddition followed by retroaldol condensation between enols of 1,3-dicarbonyls and double bonds to synthesize 1,5-dicarbonyls. Herein, we describe the [2 + 2] photocycloaddition followed by a ring-opening rearomatization reaction between electron-deficient 2-methylene-azaarenes and double bonds, taking advantage of the ability of these heterocyclic derivatives to form the corresponding pseudo-enamine intermediate. The procedure shows a high functional group tolerance either on the double bond or the heteroarene side and allows the presence of different electron-withdrawing groups. In addition, the wide applicability of this reaction has been demonstrated through the late-stage derivatization of several natural products. Photochemical studies, together with theoretical calculations, support a mechanism involving the photosensitization of the pseudo-enamine intermediate.