Dihaloiodoarenes: α,α-Dihalogenation of Phenylacetate Derivatives

A hypervalent iodine reagent-based α-carbonyl dihalogenation reaction is reported. Treating diazoacetate derivatives with either iodobenzene dichloride or iodotoluene difluoride results in <i>gem</i>-dichlorination or <i>gem</i>-difluorination products, respectively. The reaction is catalyzed by either Lewis acid or Lewis base activation of the aryl-λ³-iodane (ArIX₂) species and proceeds rapidly and chemoselectively to the desired <i>gem</i>-difunctionalized products in good to excellent yield

Iodide-Mediated Synthesis of Spirooxindolo Dihydrofurans from Iodonium Ylides and 3‑Alkylidene-2-oxindoles

An iodide-mediated reaction between cyclic iodonium ylides of 1,3-dicarbonyls and 3-alkylidene-2-oxindoles results in 3<i>H</i>-spiro­[furan-2,3′-indolin]-2′-ones. The reaction was tolerant to substitutions on both the alkylidene and ylide substrates and provided access to 19 new, densely functionalized polycyclic spirocycles in typically high yield

Iodide-Mediated Synthesis of Spirooxindolo Dihydrofurans from Iodonium Ylides and 3‑Alkylidene-2-oxindoles

An iodide-mediated reaction between cyclic iodonium ylides of 1,3-dicarbonyls and 3-alkylidene-2-oxindoles results in 3<i>H</i>-spiro­[furan-2,3′-indolin]-2′-ones. The reaction was tolerant to substitutions on both the alkylidene and ylide substrates and provided access to 19 new, densely functionalized polycyclic spirocycles in typically high yield

Accurate Analytic Potential and Born–Oppenheimer Breakdown Functions for MgH and MgD from a Direct-Potential-Fit Data Analysis

New high-resolution visible Fourier transform emission spectra of the <i>A</i> ²Π → <i>X</i> ²Σ⁺ and <i>B</i>′ ²Σ⁺ → <i>X</i> ²Σ⁺ systems of ²⁴MgD and of the <i>B</i>′ ²Σ⁺ → <i>X</i> ²Σ⁺ systems of ^25,26MgD and ^25,26MgH have been combined with earlier results for ²⁴MgH in a multi-isotopologue direct-potential-fit analysis to yield improved analytic potential energy and Born–Oppenheimer breakdown functions for the ground <i>X</i> ²Σ⁺ state of MgH. Vibrational levels of the ground state of ²⁴MgD were observed up to <i>v</i>″ = 15, which is bound by only 30.6 ± 0.10 cm^–1. Including deuteride and minor magnesium isotopologue data allowed us also to determine the adiabatic Born–Oppenheimer breakdown effects in this molecule. The fitting procedure used the recently developed Morse/Long-Range (MLR) potential energy function, whose asymptotic behavior incorporates the correct inverse-power form. A spin-splitting radial correction function to take account of the ²Σ spin–rotation interaction was also determined. Our refined value for the ground-state dissociation energy of the dominant isotopologue (²⁴MgH) is D_e = 11 104.25 ± 0.8 cm ^–1, in which the uncertainty also accounts for the model dependence of the fitted D_e values for a range of physically acceptable fits. We were also able to determine the marked difference in the well depths of ²⁴MgH and ²⁴MgD (with the deuteride potential curve being 7.58 ± 0.30 cm^–1 deeper than that of the hydride) as well as smaller well-depth differences for the minor ^25,26Mg isotopologues. This analytic potential function also predicts that the highest bound level of ²⁴MgD is <i>v</i>″ = 16 and that it is bound by only 2.73 ± 0.10 cm^–1

Accurate Analytic Potential and Born–Oppenheimer Breakdown Functions for MgH and MgD from a Direct-Potential-Fit Data Analysis

New high-resolution visible Fourier transform emission spectra of the <i>A</i> ²Π → <i>X</i> ²Σ⁺ and <i>B</i>′ ²Σ⁺ → <i>X</i> ²Σ⁺ systems of ²⁴MgD and of the <i>B</i>′ ²Σ⁺ → <i>X</i> ²Σ⁺ systems of ^25,26MgD and ^25,26MgH have been combined with earlier results for ²⁴MgH in a multi-isotopologue direct-potential-fit analysis to yield improved analytic potential energy and Born–Oppenheimer breakdown functions for the ground <i>X</i> ²Σ⁺ state of MgH. Vibrational levels of the ground state of ²⁴MgD were observed up to <i>v</i>″ = 15, which is bound by only 30.6 ± 0.10 cm^–1. Including deuteride and minor magnesium isotopologue data allowed us also to determine the adiabatic Born–Oppenheimer breakdown effects in this molecule. The fitting procedure used the recently developed Morse/Long-Range (MLR) potential energy function, whose asymptotic behavior incorporates the correct inverse-power form. A spin-splitting radial correction function to take account of the ²Σ spin–rotation interaction was also determined. Our refined value for the ground-state dissociation energy of the dominant isotopologue (²⁴MgH) is D_e = 11 104.25 ± 0.8 cm ^–1, in which the uncertainty also accounts for the model dependence of the fitted D_e values for a range of physically acceptable fits. We were also able to determine the marked difference in the well depths of ²⁴MgH and ²⁴MgD (with the deuteride potential curve being 7.58 ± 0.30 cm^–1 deeper than that of the hydride) as well as smaller well-depth differences for the minor ^25,26Mg isotopologues. This analytic potential function also predicts that the highest bound level of ²⁴MgD is <i>v</i>″ = 16 and that it is bound by only 2.73 ± 0.10 cm^–1

Accurate Analytic Potential and Born–Oppenheimer Breakdown Functions for MgH and MgD from a Direct-Potential-Fit Data Analysis

New high-resolution visible Fourier transform emission spectra of the <i>A</i> ²Π → <i>X</i> ²Σ⁺ and <i>B</i>′ ²Σ⁺ → <i>X</i> ²Σ⁺ systems of ²⁴MgD and of the <i>B</i>′ ²Σ⁺ → <i>X</i> ²Σ⁺ systems of ^25,26MgD and ^25,26MgH have been combined with earlier results for ²⁴MgH in a multi-isotopologue direct-potential-fit analysis to yield improved analytic potential energy and Born–Oppenheimer breakdown functions for the ground <i>X</i> ²Σ⁺ state of MgH. Vibrational levels of the ground state of ²⁴MgD were observed up to <i>v</i>″ = 15, which is bound by only 30.6 ± 0.10 cm^–1. Including deuteride and minor magnesium isotopologue data allowed us also to determine the adiabatic Born–Oppenheimer breakdown effects in this molecule. The fitting procedure used the recently developed Morse/Long-Range (MLR) potential energy function, whose asymptotic behavior incorporates the correct inverse-power form. A spin-splitting radial correction function to take account of the ²Σ spin–rotation interaction was also determined. Our refined value for the ground-state dissociation energy of the dominant isotopologue (²⁴MgH) is D_e = 11 104.25 ± 0.8 cm ^–1, in which the uncertainty also accounts for the model dependence of the fitted D_e values for a range of physically acceptable fits. We were also able to determine the marked difference in the well depths of ²⁴MgH and ²⁴MgD (with the deuteride potential curve being 7.58 ± 0.30 cm^–1 deeper than that of the hydride) as well as smaller well-depth differences for the minor ^25,26Mg isotopologues. This analytic potential function also predicts that the highest bound level of ²⁴MgD is <i>v</i>″ = 16 and that it is bound by only 2.73 ± 0.10 cm^–1

Accurate Analytic Potential and Born–Oppenheimer Breakdown Functions for MgH and MgD from a Direct-Potential-Fit Data Analysis

New high-resolution visible Fourier transform emission spectra of the <i>A</i> ²Π → <i>X</i> ²Σ⁺ and <i>B</i>′ ²Σ⁺ → <i>X</i> ²Σ⁺ systems of ²⁴MgD and of the <i>B</i>′ ²Σ⁺ → <i>X</i> ²Σ⁺ systems of ^25,26MgD and ^25,26MgH have been combined with earlier results for ²⁴MgH in a multi-isotopologue direct-potential-fit analysis to yield improved analytic potential energy and Born–Oppenheimer breakdown functions for the ground <i>X</i> ²Σ⁺ state of MgH. Vibrational levels of the ground state of ²⁴MgD were observed up to <i>v</i>″ = 15, which is bound by only 30.6 ± 0.10 cm^–1. Including deuteride and minor magnesium isotopologue data allowed us also to determine the adiabatic Born–Oppenheimer breakdown effects in this molecule. The fitting procedure used the recently developed Morse/Long-Range (MLR) potential energy function, whose asymptotic behavior incorporates the correct inverse-power form. A spin-splitting radial correction function to take account of the ²Σ spin–rotation interaction was also determined. Our refined value for the ground-state dissociation energy of the dominant isotopologue (²⁴MgH) is D_e = 11 104.25 ± 0.8 cm ^–1, in which the uncertainty also accounts for the model dependence of the fitted D_e values for a range of physically acceptable fits. We were also able to determine the marked difference in the well depths of ²⁴MgH and ²⁴MgD (with the deuteride potential curve being 7.58 ± 0.30 cm^–1 deeper than that of the hydride) as well as smaller well-depth differences for the minor ^25,26Mg isotopologues. This analytic potential function also predicts that the highest bound level of ²⁴MgD is <i>v</i>″ = 16 and that it is bound by only 2.73 ± 0.10 cm^–1

Accurate Analytic Potential and Born–Oppenheimer Breakdown Functions for MgH and MgD from a Direct-Potential-Fit Data Analysis

New high-resolution visible Fourier transform emission spectra of the <i>A</i> ²Π → <i>X</i> ²Σ⁺ and <i>B</i>′ ²Σ⁺ → <i>X</i> ²Σ⁺ systems of ²⁴MgD and of the <i>B</i>′ ²Σ⁺ → <i>X</i> ²Σ⁺ systems of ^25,26MgD and ^25,26MgH have been combined with earlier results for ²⁴MgH in a multi-isotopologue direct-potential-fit analysis to yield improved analytic potential energy and Born–Oppenheimer breakdown functions for the ground <i>X</i> ²Σ⁺ state of MgH. Vibrational levels of the ground state of ²⁴MgD were observed up to <i>v</i>″ = 15, which is bound by only 30.6 ± 0.10 cm^–1. Including deuteride and minor magnesium isotopologue data allowed us also to determine the adiabatic Born–Oppenheimer breakdown effects in this molecule. The fitting procedure used the recently developed Morse/Long-Range (MLR) potential energy function, whose asymptotic behavior incorporates the correct inverse-power form. A spin-splitting radial correction function to take account of the ²Σ spin–rotation interaction was also determined. Our refined value for the ground-state dissociation energy of the dominant isotopologue (²⁴MgH) is D_e = 11 104.25 ± 0.8 cm ^–1, in which the uncertainty also accounts for the model dependence of the fitted D_e values for a range of physically acceptable fits. We were also able to determine the marked difference in the well depths of ²⁴MgH and ²⁴MgD (with the deuteride potential curve being 7.58 ± 0.30 cm^–1 deeper than that of the hydride) as well as smaller well-depth differences for the minor ^25,26Mg isotopologues. This analytic potential function also predicts that the highest bound level of ²⁴MgD is <i>v</i>″ = 16 and that it is bound by only 2.73 ± 0.10 cm^–1

Electrophile Scanning Reveals Reactivity Hotspots for the Design of Covalent Peptide Binders

Protein–protein interactions (PPIs) are intriguing targets in drug discovery and development. Peptides are well suited to target PPIs, which typically present with large surface areas lacking distinct features and deep binding pockets. To improve binding interactions with these topologies and advance the development of PPI-focused therapeutics, potential ligands can be equipped with electrophilic groups to enable binding through covalent mechanisms of action. We report a strategy termed electrophile scanning to identify reactivity hotspots in a known peptide ligand and demonstrate its application in a model PPI. Cysteine mutants of a known ligand are used to install protein-reactive modifiers via a palladium oxidative addition complex (Pd-OAC). Reactivity hotspots are revealed by cross-linking reactions with the target protein under physiological conditions. In a model PPI with the 9-mer peptide antigen VL9 and major histocompatibility complex (MHC) class I protein HLA-E, we identify two reactivity hotspots that afford up to 87% conversion to the protein–peptide conjugate within 4 h. The reactions are specific to the target protein in vitro and dependent on the peptide sequence. Moreover, the cross-linked peptide successfully inhibits molecular recognition of HLA-E by CD94–NKG2A possibly due to structural changes enacted at the PPI interface. The results illustrate the potential application of electrophile scanning as a tool for rapid discovery and development of covalent peptide binders