Two brominated 10,10-dimethylisocorrole (10-DMIC) derivatives containing Pd­(II) centers have been prepared and characterized. These compounds were prepared via bromination of 10,10-dimethylbiladiene-based oligotetrapyrroles. Bromination of free base 10,10-dimethylbiladiene (DMBil1) followed by metalation with Pd­(OAc)2, as well as bromination of the corresponding Pd­(II) dimethylbiladiene complex (Pd­[DMBil1]) provide routes to Pd­(II) hexabromo-10,10-dimethyl-5,15-bis­(pentafluorophenyl)-isocorrole (Pd­[10-DMIC-Br6 ]) and Pd­(II) octabromo-10,10-dimethyl-5,15-bis­(pentafluorophenyl)-isocorrole (Pd­[10-DMIC-Br8 ]). The solid-state structures of the two brominated isocorrole complexes are presented, as is that for a new decabrominated dimethylbiladiene derivative (DMBil-Br10 ). The electronic and spectroscopic properties of the brominated biladiene and isocorrole derivatives were probed using a combination of voltammetric methods and steady-state UV–vis absorption and emission experiments. Data obtained from these experiments allow the properties of the brominated biladiene and isocorrole derivatives to be compared to previously studied biladiene derivatives (i.e., DMBil1 and Pd­[DMBil1]). CV and DPV experiments demonstrate that Pd­[10-DMIC-Br6] and Pd­[10-DMIC-Br8] support well-behaved multielectron redox chemistry, similar to that which has been observed for other nonaromatic tetrapyrroles containing sp3-hybridized meso-carbons. Spectroscopic experiments reveal that bromination of the dimethylbiladiene core shifts this system’s UV–vis absorption profile to lower energy and that the dimethylisocorrole complexes support panchromatic absorption profiles that extend across the UV–vis and into the near-IR region. Photosensitization experiments demonstrate that unlike previously studied Pd­(II) biladiene constructs, DMBil-Br10 , Pd­[10-DMIC-Br6], and Pd­[10-DMIC-Br8] support limited triplet excited state chemistry with O2, indicating that the novel nonaromatic tetrapyrrole derivatives described in this work may be best suited for applications other than singlet oxygen sensitization.

The metalation chemistry of the phlorin, which is a non-aromatic tetrapyrrole macrocycle containing a single sp3-hybridized meso-carbon has remained underdeveloped, as compared to that of more traditional tetrapyrroles such as porphyrins, corroles and phthalocyanines. There have been few prior efforts to prepare metallophlorins, and those that have been reported have relied on either reduction or nucleophilic attack of parent metalloporphyrins, rather than direct metalation of freebase phlorin constructs. In this work, an alternate synthetic approach for preparation of gold(III) phlorin complexes that involves the first direct metalation of two different freebase phlorin derivatives (3H(Phl[Formula: see text] and 3H(Phl[Formula: see text] with AuBr3 to produce the stable and fully isolable gold(III) phlorin complexes Au(Phl[Formula: see text] and Au(Phl[Formula: see text] is reported. The first structural characterization of a metallophlorin bearing geminal dimethyl substituents at the sp3-hybridized meso-carbon via X-ray crystallography is also reported. In addition to the preparation of Au(Phl[Formula: see text] and Au(Phl[Formula: see text], the UV-vis absorption and redox properties of these two gold(III) phlorins in comparison to those of their freebase homologues is also detailed. Notably, the metallophlorins are characterized by panchromatic absorbance profiles and intense and broad bands that span the long-visible and into the near-IR regions, as well as two fully reversible oxidation and reduction waves as probed by cyclic voltammetry. Finally, the chlorination of Au(Phl[Formula: see text] using PhI(Cl[Formula: see text] was probed and it was found that this regioslective reaction generates monochlorinated (Au(Phl[Formula: see text]Cl)) and dichlorinated (Au(Phl[Formula: see text]Cl[Formula: see text] products, which were both structurally characterized by X-ray crystallography.

A set of Pd(II) biladiene complexes bearing different combinations of methyl-and phenyl-substituents on the sp 3 -hybridized meso-carbon (the 10-position of the biladiene framework) was prepared and studied. In addition to a previously described Pd(II) biladiene complex bearing geminal dimethyl substituents a the 10-position (Pd[DMBil]), homologous Pd(II) biladienes bearing geminal methyl and phenyl substituents (Pd[MPBil1]) and geminal diphenyl groups-(Pd[DPBil1]) were prepared and structurally characterized. Detailed electrochemical as well as steady-state and time-resolved spectroscopic experiments were undertaken to evaluate the influence of the substituents on the biladiene's tetrahedral meso-carbon. Although all three biladiene homologues are isostructural, Pd[MPBil1] and Pd[DPBil1] display more intense absorption profiles that shift slightly toward lower energies as geminal methyl groups are replaced by phenyl rings. All three biladiene homologues support a triplet photochemistry, and replacement of the geminal dimethyl substituents of Pd[DMBil1] (Φ Δ = 54%) with phenyl groups improves the ability of Pd[MPBil1] (Φ Δ = 76%) and Pd[DPBil1] (Φ Δ = 66%) to sensitize 1 O 2 . Analysis of the excited-state dynamics of the Pd(II) biladienes by transient absorption spectroscopy shows that each complex supports a long-lived triplet excited-state (i.e., τ > 15 μs for each homologue) but that the ISC quantum yields (Φ T ) varied as a function of biladiene substitution. The observed trend in ISC efficiency matches that for singlet oxygen sensitization quantum yields (Φ Δ ) across the biladiene series considered in this work. The results of this study provide new insights to guide future development of biladiene based agents for PDT and other photochemical applications.

4-Substitution on prolined irectly impactsp rotein main chain conformational preferences.T he structurale ffects of N-acyl substitution and of 4-substitution were examined by NMR spectroscopy and X-ray crystallography on minimal molecules with ap roline 4S-nitrobenzoate.T he effects of N-acyl substitution on conformation werea ttenuated in the 4S-nitrobenzoate context, duet ot he minimal role of the n!p*i nteraction in stabilizing extended conformations. By X-ray crystallography,a ne xtended conformation was observedf or most molecules. The formyl derivative adopted a d conformation that is observed at the i + 2p osition of b-turns.C omputational analysis indicated that the structures observed crystallographically represent the inher-ent conformational preferences of 4S-substituted prolines with electron-withdrawing4-position substituents. The divergent conformational preferences of 4R-a nd 4S-substituted proliness uggest their wider structure-specific application in molecular design. In particular,t he proline endo ring pucker favored by 4S-substituted prolines uniquelyp romotes the d conformation [(f, y) % (À808,0 8)] found in b-turns.I nc ontrast to other acyl capping groups, the pivaloyl group strongly promoted trans amide bond and polyproline II helix conformation, with ac lose n!p*i nteraction in the crystalline state, despite the endo ring pucker,s uggesting its special capabilities in promoting compactc onformations in f due to its strongly electron-donatingc haracter.[a] N.Supporting information (including experimentalprocedures, NMR data on 3-9,N OESY spectra for 7 and 9,X -ray crystallographic data, additional analysis of computational data, 1 Ha nd 13 CNMR spectraf or all new compounds, and coordinates for all geometry-optimized structures) and the ORCID identification number(s) for the author(s) of this article can be found under:https://doi.

Photodynamic therapy (PDT), which involves the photoinduced sensitization of singlet oxygen, is an attractive treatment for certain types of cancer. The development of new photochemotherapeutic agents remains an important area of research. Macrocyclic tetrapyrrole compounds including porphyrins, phthalocyanines, chlorins, and bacteriochlorins have been pursued as sensitizers of singlet oxygen for PDT applications but historically are difficult to prepare/purify and can also suffer from high nonspecific dark toxicity, poor solubility in biological media, and/or slow clearance from biological tissues. In response to these shortcomings, we have developed a series of novel linear tetrapyrrole architectures complexed to late transition metals as potential PDT agents. We find that these dimethylbiladiene (DMBil1) tetrapyrrole complexes can efficiently photosensitize generation of 1 O 2 oxygen upon irradiation with visible light. To extend the absorption profile of the DMBil1 platform, alkynyl−aryl groups have been conjugated to the periphery of the tetrapyrrole using Sonogashira methods. Derivatives of this type containing ancillary phenyl (DMBil−PE), naphthyl (DMBil−NE), and anthracenyl (DMBil−AE) groups have been prepared and characterized. In addition to structurally characterizing Pd[DMBil−NE] and Pd[DMBil−AE], we find that extension of the tetrapyrrole conjugation successfully red-shifts the absorption of the DMBil−Ar family of biladienes further into the phototherapeutic window (i.e., 600−900 nm). Photochemical sensitization studies demonstrate that our series of new palladium biladiene complexes (Pd[DMBil−Ar]) can sensitize the formation of 1 O 2 with quantum yields in the range Φ Δ = 0.59−0.73 upon irradiation with light of λ ≥ 650 nm. The improved absorption properties of the Pd[DMBil−Ar] complexes in the phototherapeutic window, together with their high 1 O 2 quantum yields, highlight the promise of these compounds as potential agents for PDT.