Postpolymerization Functionalization of Copolymers Produced from Carbon Dioxide and 2‑Vinyloxirane: Amphiphilic/Water-Soluble CO₂‑Based Polycarbonates

Common CO₂-based polycarbonates are known to be highly hydrophobic, and this “inert” property makes them difficult for the covalent immobilization of bioactive molecules. A practical method for modifying polymers is to introduce various functional groups that permit decoration of polymer chains with bioactive substances. In this report, CO₂-based poly­(2-vinyloxirane carbonate) (PVIC) with more than 99% carbonate linkages is isolated from the CO₂/2-vinyloxirane alternating copolymerization catalyzed by the bifunctional catalyst [(1<i>R</i>,2<i>R</i>)-SalenCo­(III)­(DNP)₂] (<b>1</b>) (DNP = 2,4-dinitrophenolate) bearing a quaternary ammonium salt on the ligand framework. It was also observed that the presence of propylene oxide significantly activates 2-vinyloxirane for incorporation into the polymer chain as well as inhibits the formation of cyclic carbonate in the terpolymerization process. DSC studies demonstrate that the glass transition temperature (<i>T</i>_g) decreases with the increase in the content of vinyl groups in the polycarbonate. By way of thiol–ene coupling, showing mainly “click” characteristics and nearly quantitative yields, amphiphilic polycarbonates (PVIC-OH and PVIC-COOH) with multiple hydroxy or carboxy functionalities have been prepared, providing suitable reactivities for further modifications (ring-opening of l-aspartic acid anhydride hydrochloride salt and deprotonation by aqueous ammonium hydroxide (NH₄OH_(aq))) to successfully isolate the water-soluble CO₂-based polycarbonate PVIC-COONH₄, and the PVIC-OH-Asp polymer which shows particles dispersed in water with an average hydrodynamic diameter <i>D</i>_n = 32.2 ± 8.8 nm. It is presumed that this emerging class of amphiphilic/water-soluble polycarbonates could embody a powerful platform for bioconjugation and drug conjugation. In contrast to lower <i>T</i>_gs of PVIC, (PVIC-<i>co</i>-PC), PVIC-OH, and PVIC-COOH, the polycarbonates PVIC-OH-Asp and PVIC-COONH₄ show higher <i>T</i>_gs as a consequence of their intrinsic ionic property (ammonium salts)

Environmentally Benign CO₂‑Based Copolymers: Degradable Polycarbonates Derived from Dihydroxybutyric Acid and Their Platinum–Polymer Conjugates

(<i>S</i>)-3,4-Dihydroxybutyric acid ((<i>S</i>)-3,4-DHBA), an endogenous straight chain fatty acid, is a normal human urinary metabolite and can be obtained as a valuable chiral biomass for synthesizing statin-class drugs. Hence, its epoxide derivatives should serve as promising monomers for producing biocompatible polymers via alternating copolymerization with carbon dioxide. In this report, we demonstrate the production of poly­(<i>tert</i>-butyl 3,4-dihydroxybutanoate carbonate) from <i>racemic-tert</i>-butyl 3,4-epoxybutanoate (<i>rac</i>-^<i>t</i>Bu 3,4-EB) and CO₂ using bifunctional cobalt­(III) salen catalysts. The copolymer exhibited greater than 99% carbonate linkages, 100% head-to-tail regioselectivity, and a glass-transition temperature (<i>T</i>_g) of 37 °C. By way of comparison, the similarly derived polycarbonate from the sterically less congested monomer, methyl 3,4-epoxybutanoate, displayed 91.8% head-to-tail content and a lower <i>T</i>_g of 18 °C. The <i>tert</i>-butyl protecting group of the pendant carboxylate group was removed using trifluoroacetic acid to afford poly­(3,4-dihydroxybutyric acid carbonate). Depolymerization of poly­(<i>tert</i>-butyl 3,4-dihydroxybutanoate carbonate) in the presence of strong base results in a stepwise unzipping of the polymer chain to yield the corresponding cyclic carbonate. Furthermore, the full degradation of the acetyl-capped poly­(potassium 3,4-dihydroxybutyrate carbonate) resulted in formation of the biomasses, β-hydroxy-γ-butyrolacetone and 3,4-dihydroxybutyrate, in water (pH = 8) at 37 °C. In addition, water-soluble platinum–polymer conjugates were synthesized with platinum loading of 21.3–29.5%, suggesting poly­(3,4-dihydroxybutyric acid carbonate) and related derivatives may serve as platinum drug delivery carriers

Nitrate-to-Nitrite-to-Nitric Oxide Conversion Modulated by Nitrate-Containing {Fe(NO)₂}⁹ Dinitrosyl Iron Complex (DNIC)

Nitrosylation of high-spin [Fe­(κ²-O₂NO)₄]^2<b>–</b> (<b>1</b>) yields {Fe­(NO)}⁷ mononitrosyl iron complex (MNIC) [(κ²-O₂NO)­(κ¹-ONO₂)₃Fe­(NO)]^2<b>–</b> (<b>2</b>) displaying an <i>S</i> = 3/2 axial electron paramagnetic resonance (EPR) spectrum (<i>g</i>_⊥ = 3.988 and <i>g</i>_∥ = 2.000). The thermally unstable nitrate-containing {Fe­(NO)₂}⁹ dinitrosyl iron complex (DNIC) [(κ¹-ONO₂)₂Fe­(NO)₂]^<b>–</b> (<b>3</b>) was exclusively obtained from reaction of HNO₃ and [(OAc)₂Fe­(NO)₂]^<b>–</b> and was characterized by IR, UV–vis, EPR, superconducting quantum interference device (SQUID), X-ray absorption spectroscopy (XAS), and single-crystal X-ray diffraction (XRD). In contrast to {Fe­(NO)₂}⁹ DNIC [(ONO)₂Fe­(NO)₂]^<b>–</b> constructed by two monodentate O-bound nitrito ligands, the weak interaction between Fe(1) and the distal oxygens O(5)/O(7) of nitrato-coordinated ligands (Fe(1)···O(5) and Fe(1)···O(7) distances of 2.582(2) and 2.583(2) Å, respectively) may play important roles in stabilizing DNIC <b>3</b>. Transformation of nitrate-containing DNIC <b>3</b> into N-bound nitro {Fe­(NO)}⁶ [(NO)­(κ¹-NO₂)­Fe­(S₂CNEt₂)₂] (<b>7</b>) triggered by bis­(diethylthiocarbamoyl) disulfide ((S₂CNEt₂)₂) implicates that nitrate-to-nitrite conversion may occur via the intramolecular association of the coordinated nitrate and the adjacent polarized NO-coordinate ligand <b>(</b>nitrosonium<b>)</b> of the proposed {Fe­(NO)₂}⁷ intermediate [(NO)₂(κ¹-ONO₂)­Fe­(S₂CNEt₂)₂] (<b>A</b>) yielding {Fe­(NO)}⁷ [(NO)­Fe­(S₂CNEt₂)₂] (<b>6</b>) along with the release of N₂O₄ (·NO₂) and the subsequent binding of ·NO₂ to complex <b>6</b>. The N-bound nitro {Fe­(NO)}⁶ complex <b>7</b> undergoes Me₂S-promoted O-atom transfer facilitated by imidazole to give {Fe­(NO)}⁷ complex <b>6</b> accompanied by release of nitric oxide. This result demonstrates that nitrate-containing DNIC <b>3</b> acts as an active center to modulate nitrate-to-nitrite-to-nitric oxide conversion

Insight into One-Electron Oxidation of the {Fe(NO)₂}⁹ Dinitrosyl Iron Complex (DNIC): Aminyl Radical Stabilized by [Fe(NO)₂] Motif

A reversible redox reaction ({Fe­(NO)₂}⁹ DNIC [(NO)₂Fe­(N­(Mes)­(TMS))₂]⁻ (<b>4</b>) ⇄ oxidized-form DNIC [(NO)₂Fe­(N­(Mes)­(TMS))₂] (<b>5</b>) (Mes = mesityl, TMS = trimethylsilane)), characterized by IR, UV–vis, ¹H/¹⁵N NMR, SQUID, XAS, single-crystal X-ray structure, and DFT calculation, was demonstrated. The electronic structure of the oxidized-form DNIC <b>5</b> (<i>S</i>_total = 0) may be best described as the delocalized aminyl radical [(N­(Mes)­(TMS))₂]₂^–• stabilized by the electron-deficient {Fe^III(NO^–)₂}⁹ motif, that is, substantial spin is delocalized onto the [(N­(Mes)­(TMS))₂]₂^–• such that the highly covalent dinitrosyl iron core (DNIC) is preserved. In addition to IR, EPR (<i>g</i> ≈ 2.03 for {Fe­(NO)₂}⁹), single-crystal X-ray structure (Fe–N­(O) and N–O bond distances), and Fe K-edge pre-edge energy (7113.1–7113.3 eV for {Fe­(NO)₂}¹⁰ vs 7113.4–7113.9 eV for {Fe­(NO)₂}⁹), the ¹⁵N NMR spectrum of [Fe­(¹⁵NO)₂] was also explored to serve as an efficient tool to characterize and discriminate {Fe­(NO)₂}⁹ (δ 23.1–76.1 ppm) and {Fe­(NO)₂}¹⁰ (δ −7.8–25.0 ppm) DNICs. To the best of our knowledge, DNIC <b>5</b> is the first structurally characterized tetrahedral DNIC formulated as covalent–delocalized [{Fe^III(NO^–)₂}⁹–[N­(Mes)­(TMS)]₂^–•]. This result may explain why all tetrahedral DNICs containing monodentate-coordinate ligands isolated and characterized nowadays are confined in the {Fe­(NO)₂}⁹ and {Fe­(NO)₂}¹⁰ DNICs in chemistry and biology

Insight into One-Electron Oxidation of the {Fe(NO)₂}⁹ Dinitrosyl Iron Complex (DNIC): Aminyl Radical Stabilized by [Fe(NO)₂] Motif

A reversible redox reaction ({Fe­(NO)₂}⁹ DNIC [(NO)₂Fe­(N­(Mes)­(TMS))₂]⁻ (<b>4</b>) ⇄ oxidized-form DNIC [(NO)₂Fe­(N­(Mes)­(TMS))₂] (<b>5</b>) (Mes = mesityl, TMS = trimethylsilane)), characterized by IR, UV–vis, ¹H/¹⁵N NMR, SQUID, XAS, single-crystal X-ray structure, and DFT calculation, was demonstrated. The electronic structure of the oxidized-form DNIC <b>5</b> (<i>S</i>_total = 0) may be best described as the delocalized aminyl radical [(N­(Mes)­(TMS))₂]₂^–• stabilized by the electron-deficient {Fe^III(NO^–)₂}⁹ motif, that is, substantial spin is delocalized onto the [(N­(Mes)­(TMS))₂]₂^–• such that the highly covalent dinitrosyl iron core (DNIC) is preserved. In addition to IR, EPR (<i>g</i> ≈ 2.03 for {Fe­(NO)₂}⁹), single-crystal X-ray structure (Fe–N­(O) and N–O bond distances), and Fe K-edge pre-edge energy (7113.1–7113.3 eV for {Fe­(NO)₂}¹⁰ vs 7113.4–7113.9 eV for {Fe­(NO)₂}⁹), the ¹⁵N NMR spectrum of [Fe­(¹⁵NO)₂] was also explored to serve as an efficient tool to characterize and discriminate {Fe­(NO)₂}⁹ (δ 23.1–76.1 ppm) and {Fe­(NO)₂}¹⁰ (δ −7.8–25.0 ppm) DNICs. To the best of our knowledge, DNIC <b>5</b> is the first structurally characterized tetrahedral DNIC formulated as covalent–delocalized [{Fe^III(NO^–)₂}⁹–[N­(Mes)­(TMS)]₂^–•]. This result may explain why all tetrahedral DNICs containing monodentate-coordinate ligands isolated and characterized nowadays are confined in the {Fe­(NO)₂}⁹ and {Fe­(NO)₂}¹⁰ DNICs in chemistry and biology

Electronic Structure and Transformation of Dinitrosyl Iron Complexes (DNICs) Regulated by Redox Non-Innocent Imino-Substituted Phenoxide Ligand

The coupled NO-vibrational peaks [IR νNO 1775 s, 1716 vs, 1668 vs cm–1 (THF)] between two adjacent [Fe(NO)2] groups implicate the electron delocalization nature of the singly O-phenoxide-bridged dinuclear dinitrosyliron complex (DNIC) [Fe(NO)2(μ-ON2Me)Fe(NO)2] (1). Electronic interplay between [Fe(NO)2] units and [ON2Me]− ligand in DNIC 1 rationalizes that “hard” O-phenoxide moiety polarizes iron center(s) of [Fe(NO)2] unit(s) to enforce a “constrained” π-conjugation system acting as an electron reservoir to bestow the spin-frustrated {Fe(NO)2}9-{Fe(NO)2}9-[·ON2Me]2– electron configuration (Stotal = 1/2). This system plays a crucial role in facilitating the ligand-based redox interconversion, working in harmony to control the storage and redox-triggered transport of the [Fe(NO)2]10 unit, while preserving the {Fe(NO)2}9 core in DNICs {Fe(NO)2}9-[·ON2Me]2– [K-18-crown-6-ether)][(ON2Me)Fe(NO)2] (2) and {Fe(NO)2}9-[·ON2Me] [(ON2Me)Fe(NO)2][PF6] (3). Electrochemical studies suggest that the redox interconversion among [{Fe(NO)2}9-[·ON2Me]2–] DNIC 3 ↔ [{Fe(NO)2}9-[ON2Me]−] ↔ [{Fe(NO)2}9-[·ON2Me]] DNIC 2 are kinetically feasible, corroborated by the redox shuttle between O-bridged dimerized [(μ-ONMe)2Fe2(NO)4] (4) and [K-18-crown-6-ether)][(ONMe)Fe(NO)2] (5). In parallel with this finding, the electronic structures of [{Fe(NO)2}9-{Fe(NO)2}9-[·ON2Me]2–] DNIC 1, [{Fe(NO)2}9-[·ON2Me]2–] DNIC 2, [{Fe(NO)2}9-[·ON2Me]] DNIC 3, [{Fe(NO)2}9-[ONMe]−]2 DNIC 4, and [{Fe(NO)2}9-[·ONMe]2–] DNIC 5 are evidenced by EPR, SQUID, and Fe K-edge pre-edge analyses, respectively

{Fe(NO)₂}⁹ Dinitrosyl Iron Complex Acting as a Vehicle for the NO Radical

To carry and deliver nitric oxide with a controlled redox state and rate is crucial for its pharmaceutical/medicinal applications. In this study, the capability of cationic {Fe­(NO)₂}⁹ dinitrosyl iron complexes (DNICs) [(^RDDB)­Fe­(NO)₂]⁺ (R = Me, Et, Iso; ^RDDB = <i>N,N</i>′-bis­(2,6-dialkylphenyl)-1,4-diaza-2,3-dimethyl-1,3-butadiene) carrying nearly unperturbed nitric oxide radical to form [(^RDDB)­Fe­(NO)₂(^•NO)]⁺ was demonstrated and characterized by IR, UV–vis, EPR, NMR, and single-crystal X-ray diffractions. The unique triplet ground state of [(^RDDB)­Fe­(NO)₂(^•NO)]⁺ results from the ferromagnetic coupling between two strictly orthogonal orbitals, one from Fe d_<i>z</i>² and the other a π*_op orbital of a unique bent axial NO ligand, which is responsible for the growth of a half-field transition (Δ<i>M</i>_S = 2) from 70 to 4 K in variable-temperature EPR measurements. Consistent with the NO radical character of coordinated axial NO ligand in complex [(^MeDDB)­Fe­(NO)₂(^•NO)]⁺, the simple addition of MeCN/H₂O into CH₂Cl₂ solution of complexes [(^RDDB)­Fe­(NO)₂(^•NO)]⁺ at 25 °C released NO as a neutral radical, as demonstrated by the formation of [S₅Fe­(NO)₂]⁻ from [S₅Fe­(μ-S)₂FeS₅]^2–