IU Indianapolis ScholarWorks :: Browsing by Author "Deng, Yongming"

Browsing by Author "Deng, Yongming"

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Greener Photoredox-Catalyzed Phosphonations of Aryl Halides
(2024-05) Kelley, Alexandra S.; Laulhe, Sébastien; Minto, Robert; Deng, Yongming
Aromatic phosphonates and phosphine oxides are highly desirable synthetic targets used in pharmaceuticals, natural products, agrichemicals, catalysis, and materials science. While a variety of aromatic precursors have been used to access these motifs, aryl halides remain one of the most desirable coupling partners owing to their low cost, commercial availability, and regioselective reactivity. Traditional phosphonation often requires the use of harsh reductants in the presence of liquid ammonia, which are caustic and pose incredible environmental concerns. Milder, transition metal-catalyzed approaches have been developed, but can be limited by air sensitivity, cost, low reaction selectivity, and low functional group compatibility. Photoredox catalysis has been significantly advanced in the past decade in the pursuit of greener, more sustainable avenues to facilitate desirable reaction transformations under mild conditions. These methods most commonly use a dual catalytic strategy in which a metal is paired with an organocatalyst. While these approaches enable facile phosphonation of a variety of aromatic precursors, the metals and organocatalysts used are often expensive and toxic. Indeed, there remains unexplored chemical space for transition metal-free photoredox-catalyzed aryl C-P bond formations. Herein, we present a series of transition metal-free, photoredox-catalyzed approaches to the phosphonation of aryl halides. The approaches and mechanistic works will be discussed in the following order: First, the discovery that 10H-phenothiazine (PTZ) enables the transition metal-free phosphonation of aryl halides using trialkyl phosphites will be presented. PTZ serves as a photocatalyst capable of reducing the aryl halide to access aryl radicals, which readily couple with phosphite esters. This transformation exhibits broad functional group tolerance in good to excellent yields. Then, photoredox catalysis by PTZ enables the formation of unsymmetrical aromatic phosphine oxides using triphenylphosphine (PPh3) and aryl halides. This is the first work in which PPh3 has been used as the starting material, and the reaction proceeds via the alkaline hydrolysis of quaternary phosphonium salts. The final work exhibits novel photocatalytic activity of N-heterocyclic carbenes (NHC) to activate aryl halides, form aryl radicals, and enable phosphonation. This method displays broad functional group tolerance under mild conditions and highlights its untapped synthetic utility as a photocatalyst.
Investigating the Photophysical Properties of Potential Organic Lead Sensors
(2023) Quinones, Carlos; Basu, Partha; Deng, Yongming; Pu , Jingzhi
LeadGlow (LG) was reported in 2009 for its ability to both sensitively and selectively detect Pb2+ in aqueous solutions. Utilizing the synthetic approach of LG, it is possible to generate a class of novel fluorophores. A derivative of first-generation LG was synthesized and reported here for the first time, intuitively named LG2. Both compounds contain interesting photophysical properties that have not been extensively researched prior to this work. Because of this, photophysical properties of both LG and LG2 are unveiled here for the first time. These properties were investigated by determinations of quantum yield (QY), average fluorescence lifetime, and DFT calculations. LG was found to have a higher QY (0.057) than LG2 (0.011); however, LG2 displays an average fluorescence lifetime (3.186 ns) 5x greater than that of LG. Both LG and LG2 are synthesized via Hg2+-facilitated desulfurization of their respective thiocarbonyls, resulting in a turn-on fluorescence feature. The thiocarbonyl-containing fluorophores (SLG and SLG2) display quenched fluorescence compared to their oxo-derivatives (LG and LG2), this work attempts to investigate the mechanism(s) responsible. A whole class of LeadGlow compounds can be synthesized and could be potentially used as fluorescence-based sensors.
Machine Learning Facilitated Quantum Mechanic/Molecular Mechanic Free Energy Simulations
(2023-08) Snyder, Ryan; Pu, Jingzhi; Naumann, Christoph; Webb, Ian; Deng, Yongming
Bridging the accuracy of ab initio (AI) QM/MM with the efficiency of semi-empirical (SE) QM/MM methods has long been a goal in computational chemistry. This dissertation presents four ∆-Machine learning schemes aimed at achieving this objective. Firstly, the incorporation of negative force observations into the Gaussian process regression (GPR) model, resulting in GPR with derivative observations, demonstrates the remarkable capability to attain high-quality potential energy surfaces, accurate Cartesian force descriptions, and reliable free energy profiles using a training set of just 80 points. Secondly, the adaptation of the sparse streaming GPR algorithm showcases the potential of memory retention from previous phasespace, enabling energy-only models to converge using simple descriptors while faithfully reproducing high-quality potential energy surfaces and accurate free energy profiles. Thirdly, the utilization of GPR with atomic environmental vectors as input features proves effective in enhancing both potential energy surface and free energy description. Furthermore, incorporating derivative information on solute atoms further improves the accuracy of force predictions on molecular mechanical (MM) atoms, addressing discrepancies arising from QM/MM interaction energies between the target and base levels of theory. Finally, a comprehensive comparison of three distinct GPR schemes, namely GAP, GPR with an average kernel, and GPR with a system-specific sum kernel, is conducted to evaluate the impact of permutational invariance and atomistic learning on the model’s quality. Additionally, this dissertation introduces the adaptation of the GAP method to be compatible with the sparse variational Gaussian processes scheme and the streaming sparse GPR scheme, enhancing their efficiency and applicability. Through these four ∆-Machine learning schemes, this dissertation makes significant contributions to the field of computational chemistry, advancing the quest for accurate potential energy surfaces, reliable force descriptions, and informative free energy profiles in QM/MM simulations.
Molecular dynamics simulations of spore photoproduct containing DNA systems
(2023-05) Hege, Mellisa; Pu, Jingzhi; Blacklock, Brenda; Georgiadis, Millie; Deng, Yongming
Bacterial endospores have been a topic of research interest over the last several decades given their high resistance to ultraviolet (UV) damage. Unlike vegetative bacterial cells, which form cyclobutane pyrimidine dimers (CPD) and pyrimidine 6-4 pyrimidone photoproducts (6-4PPs) as the major product upon UV irradiation, endospore bacteria form a spore photoproduct (5-(R-thyminyl)-5,6-dihydrothymine or SP) as the major product. Vegetative bacteria cells are subject to regular cell activities and processes such as division and deoxyribonucleic acid (DNA) replication, which are prone to damage from UV exposure. However, in endospores, which have a largely anhydrous inner environment, the DNA remains dormant when bound to spore-specific small acid-soluble proteins (SASP) and dipicolinic acid, making spores highly resistant to radiation, heat, desiccation, and chemical harm. During spore germination, SP lesions in DNA are repaired by a distinctive repair enzyme, spore photoproduct lyase (SPL). In this thesis, molecular dynamics (MD) simulations were carried out to (i) examine how the formation of the SP lesion in DNA affects the global and local structural properties of duplex DNA and (ii) study how this lesion is recognized and repaired in endospore. The first part of this work was focused on designing and developing a structurally and dynamically stable model for dinucleotide SP molecule (TpT), which was subsequently used as an SP patch incorporated into duplex DNA. Computationally, this requires modifications of the bond and nonbonded force field parameters. The stability of the patch and developed parameters was tested via solution-phase MD simulations for the SP lesion incorporated within the B-DNA dodecamer duplex (PDB 463B). The second part involved applying the new SP patch to simulate the crystallographic structure of the DNA oligomer containing SP lesions. Solution-phase MD simulations were performed for the SP-containing DNA oligomers (modeled based on PDB 4M94) and compared to the simulations of the native structure (PDB 4M95). Our analysis of the MD trajectories revealed a range of SP-induced structural and dynamical changes, including the weakened hydrogen bonds at the SP sites, increased DNA bending, and distinct conformational stability and distribution. In the third part of this thesis project, we carried out MD simulations of SP-containing DNA bound with SASPs to examine how the DNA interacts differently with SASP in the presence and absence of the SP lesion. The simulation results suggested decreased electrostatic and hydrogen bonding interactions between SASP and the damaged DNA at the SP site compared to the undamaged DNA-protein complex. In addition, decreased helicity percentage was observed in the SASPs that directly interact with the SP lesion. The last part of this this thesis work focused on the SP-dimer flipping mechanism, as the lesion is likely flipped out to its extrahelical state to be recognized and repaired by SPL. Using steered molecular dynamic (SMD) simulations and a pseudo-dihedral angle reaction coordinate, we obtained possible SP flipping pathways both in the presence and absence of SASP. Collectively, these simulation results lend new perspectives toward understanding the unique behavior of the SP lesion within the DNA duplex and the nucleoprotein complex. They also provide new insights into how the SP lesion is efficiently recognized and repaired during spore germination.
Organic Photoredox Catalyzed Direct Hydroamination of Ynamides with Azoles
(Wiley, 2022-03-15) Wang, Ban; Mccabe, Gavin E.; Parrish, Mitchell J.; Singh, Jujhar; Zeller, Matthias; Deng, Yongming; Chemistry and Chemical Biology, School of Science
Disclosed herein is a photoinduced selective hydroamination of ynamides with nitrogen heteroaromatic nucleophiles. By using an organocatalytic photoredox system, a direct method to construct a diverse of (Z)-α-azole enamides from ynamides and pyrazoles, as well as triazoles, benzotriazoles, indazoles, and tetrazoles, is developed, thus providing a photocatalytically synthetic route to heterocyclic motifs common in medicinal agents. Based on the mechanistic studies, the hydroamination is postulated to operate via a mechanism in which the single-electron oxidation of ynamide and the intermediacy of an alkyne radical cation, is responsible for the observed reactivity.
Phosphonium-Salt Mediated Activation of C-O Bonds: Applications and Mechanistic Studies
(2023-05) Irving, Charles D.; Laulhé, Sébastien; Manicke, Nicholas; Minto, Robert; Deng, Yongming
The C-O single bond is found in numerous functional motifs including carboxylic acids, alcohols, and ethers. These compounds represent ideal precursors towards C-X (X = C, H, or heteroatom) bond formation due to their inherent stability and abundance in nature. As such, synthetic chemists continue to develop new technologies for the transformation of these precursors into biologically useful targets such as amides and amines. However, due to the stability of the C-O single bond, accessing such targets remains a consistent challenge. The activation of the carboxylic acids towards peptide synthesis has been facilitated through various coupling agents, including organoboron and transition metal catalysts. However, coupling agents can generate stochiometric, difficult-to-remove, toxic waste by-products. Organoboron/transition metal catalyzed condensations offer a more atom economical approach but suffer from varying degrees of optical erosion and poor sustainability. Phosphonium-based deoxyaminative technologies provide access to amines from alcohols via a phosphorus oxygen double bond formation driving force, but possesses a narrow nucleophilic nitrogen source scope, and poor atom economy. Transition metal/enzyme catalyzed “hydrogen borrowings” represent atom economical deoxyaminative alternatives. Still, their respective use of costly metals, and multiple enzymatic cascade steps severely limit the sustainability and scope of such protocols. An ambient deoxyamidation of carboxylic acids and deoxyamination of alcohols was developed through the use of N-haloimides activated by triphenylphosphine. Such technologies were found to possess broad functional tolerance and formed C-N bonds via a coupling to free amines, and the direct installment of the imide motif. Mechanistic experiments suggest that such transformations take place via the in situ generation of two separate phosphonium reactive species.
Photoinduced oxidative cyclopropanation of ene-ynamides: synthesis of 3-aza[n.1.0]bicycles via vinyl radicals
(Royal Society of Chemistry, 2021-05) Deng, Yongming; Zhang, Jason; Bankhead, Bradley; Markham, Jonathan P.; Zeller, Matthias; Chemistry and Chemical Biology, School of Science
The first photoinduced synthesis of polyfunctionalized 3-aza[n.1.0]bicycles from readily available ene-ynamides and 2,6-lutidine N-oxide using an organic acridinium photocatalyst is reported. Applying a photocatalytic strategy to the reactive distonic cation vinyl radical intermediate from ynamide, a series of bio-valuable 3-azabicycles, including diverse 3-azabicyclio[4.1.0]heptanes and 3-azabicyclo[5.1.0]octanes that are challenging to accomplish using traditional methods, have been successfully synthesized in good to high yields under mild and metal-free conditions. Mechanistic studies are consistent with the photocatalyzed single-electron oxidation of ene-ynamide and the intermediacy of a putative cationic vinyl radical in this transformation. Importantly, this strategy provides new access to the development of photocatalytic vinyl radical cascades for the synthesis of structurally sophisticated substrates.
Photoredox-Catalyzed Divergent Radical Cascade Annulations of 1,6-Enynes via Pyridine N-Oxide-Promoted Vinyl Radical Generation
(American Chemical Society, 2023) Wang, Ban; Singh, Jujhar; Deng, Yongming; Chemistry and Chemical Biology, School of Science
The divergent organophotoredox-catalyzed radical cascade annulation reactions of 1,6-enynes were developed. A series of cyclopropane-fused hetero- and carbo-bicyclic, tricyclic, and spiro-tetracyclic compounds were facilely synthesized from a broad scope of 1,6-enynes and 2,6-lutidine N-oxide under mild and metal-free conditions with blue light-emitting diode light irradiation. The cascade annulation reaction occurs with the intermediacy of a β-oxyvinyl radical, which is produced from photocatalytically generated pyridine N-oxy radical addition to the carbon-carbon triple bond.
Recent Advances in Synthetic Methods by Photocatalytic Single-Electron Transfer Chemistry of Pyridine N-Oxides
(American Chemical Society, 2024) Satheesh, Vanaparthi; Deng, Yongming; Chemistry and Chemical Biology, School of Science
By adoption of the enabling technology of modern photoredox catalysis and photochemistry, the generation of reactive and versatile pyridine N-oxy radicals can be facilely achieved from single-electron oxidation of pyridine N-oxides. This Synopsis highlights recent methodologies mediated by pyridine N-oxy radicals in developing (1) pyridine N-oxide-based hydrogen atom transfer catalysts for C(sp3)-H functionalizations and (2) β-oxyvinyl radical-mediated cascade reactions. In addition, recent research revealed that direct photoexcitation of pyridine N-oxides allowed for the generation of alkyl carbon radicals from alkylboronic acids.
The Influence of Structure on the Donor-Acceptor Properties of Metallodithiolene Complexes
(2024-08) Colston, Kyle J.; Basu, Partha; Deng, Yongming; Pu, Jingzhi; Laulhé, Sébastien
The intrinsic charge transfer properties of a given system are dictated by their electronic structure. The movement of electrons from electron rich to electron deficient moieties of a system can spur useful photophysical properties that have been utilized in the development of materials science. Such systems take advantage of redox-active ligands, which can actively participate in electron transfer, and have the versatility to function as either electron donors or acceptors in charge transfer processes. One of the most widely used family of ligands in the development of such materials is dithiolene (Dt), which can exists in two redox extremes; reduced ene-1,2-dithiolate(2-) (Dt2-) and oxidized dithione (Dt0). Dt ligands draw inspiration from the molybdenum cofactor (Moco) found in molybdenum containing enzymes that are present in all phyla of life. The Dt2- and Dt0 ligands play contrasting roles in charge transfer, however, characterization of their electronic structure when both are incorporated into a coordination complex is underexplored. Detailed computational and experimental interrogation of such complexes are presented to highlight the importance of molecular and electronic structures on their charge transfer properties. Such complexes containing a Mo core are also relevant towards the comprehension of the electronic structure of Moco. This investigation focuses on the fundamental understanding of the charger transfer properties of metallodithiolene complexes containing both Dt2- and Dt0 ligands, and progress towards the synthesis of the closest Moco analogs.

Browsing by Author "Deng, Yongming"

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