Platinum(II) alkyl complexes of chelating dibridgehead diphosphines P((CH2)n)3P (n = 14, 18, 22); facile cis/trans isomerizations interconverting gyroscope and parachute like adducts.

The gyroscope like dichloride complexes trans-Pt(Cl)2(P((CH2)n)3P) (trans-2; n = c, 14; e, 18; g, 22) and MeLi (2 equiv.) react to yield the parachute like dimethyl complexes cis-Pt(Me)2(P((CH2)n)3P) (cis-4c,e,g, 70-91%). HCl (1 equiv.) and cis-4c react to give cis-Pt(Cl)(Me)(P((CH2)14)3P) (cis-5c, 83%), which upon stirring with silica gel or crystallization affords trans-5c (89%). Similar reactions of HCl and cis-4e,g give cis/trans-5e,g mixtures that upon stirring with silica gel yield trans-5e,g. A parallel sequence with trans-2c/EtLi gives cis-Pt(Et)2(P((CH2)14)3P) (cis-6c, 85%) but subsequent reaction with HCl affords trans-Pt(Cl)(Et)(P((CH2)14)3P) (trans-7c, 45%) directly. When previously reported cis-Pt(Ph)2(P((CH2)14)3P) is treated with HCl (1 equiv.), cis- and trans-Pt(Cl)(Ph)(P((CH2)14)3P) are isolated (44%, 29%), with the former converting to the latter at 100 °C. Reactions of trans-5c and LiBr or NaI afford the halide complexes trans-Pt(X)(Me)(P((CH2)14)3P) (trans-9c, 88%; trans-10c, 87%). Thermolyses and DFT calculations that include acyclic model compounds establish trans > cis stabilities for all except the dialkyl complexes, for which energies can be closely spaced. The σ donor strengths of the non-phosphine ligands are assigned key roles in the trends. The crystal structures of cis-4c, trans-5c, trans-7c, and trans-10c are determined and analyzed together with the computed structures.

Macrocyclic Complexes Derived from Four cis-L2 Pt Corners and Four Butadiynediyl Linkers; Syntheses, Electronic Structures, and Square versus Skew Rhombus Geometries.

The dialkyl malonate derived 1,3-diphosphines R2 C(CH2 PPh2 )2 (R=a, Me; b, Et; c, n-Bu; d, n-Dec; e, Bn; f, p-tolCH2 ) are combined with (p-tol3 P)2 PtCl2 or trans-(p-tol3 P)2 Pt((C≡C)2 H)2 to give the chelates cis-(R2 C(CH2 PPh2 )2 )PtCl2 (2 a-f, 94-69 %) or cis-(R2 C(CH2 PPh2 )2 )Pt((C≡C)2 H)2 (3 a-f, 97-54 %). Complexes 3 a-d are also available from 2 a-d and excess 1,3-butadiyne in the presence of CuI (cat.) and excess HNEt2 (87-65 %). Under similar conditions, 2 and 3 react to give the title compounds [(R2 C(CH2 PPh2 )2 )[Pt(C≡C)2 ]4 (4 a-f; 89-14 % (64 % avg)), from which ammonium salts such as the co-product [H2 NEt2 ]+ Cl- are challenging to remove. Crystal structures of 4 a,b show skew rhombus as opposed to square Pt4 geometries. The NMR and IR properties of 4 a-f are similar to those of mono- or diplatinum model compounds. However, cyclic voltammetry gives only irreversible oxidations. As compared to mono-platinum or Pt(C≡C)2 Pt species, the UV-visible spectra show much more intense and red-shifted bands. Time dependent DFT calculations define the transitions and principal orbitals involved. Electrostatic potential surface maps reveal strongly negative Pt4 C16 cores that likely facilitate ammonium cation binding. Analogous electronic properties of Pt3 C12 and Pt5 C20 homologs and selected equilibria are explored computationally.

Gyroscopes and the Chemical Literature, 2002-2020: Approaches to a Nascent Family of Molecular Devices.

Research directed toward the goal of molecular gyroscopes since the coverage of a previous review (2002) is described. Such species are a subclass of molecular rotors, which are comprised of rotators and stators. Major categories include (1) systems in which a rotator is embedded in a cage-like stator reminiscent of mechanical toy gyroscopes and (2) molecules that have been engineered to crystallize with parallel rotators and voids or other features that enable the rotator to rotate in the solid state (amphidynamic crystals). Particular attention is given to structural data and strategies for the minimization of rotational barriers. Synthetic routes are also described. Some allied types of molecules and supramolecular assemblies are also treated.

Toward Frameworks with Multiple Aligned and Interactive Fe(CO)3 Rotators: Syntheses and Structures of Diiron Complexes Linked by Two trans-Diaxial α,ω-Diphosphine Ligands Ar2P(CH2)nPAr2.

Reactions of (η4-benzylideneacetone)Fe(CO)3 and the α,ω-diphosphines Ar2P(CH2)nPAr2 afford the trigonal bipyramidal diiron tetraphosphorus complexes trans,trans-(CO)3Fe[Ar2P(CH2)nPAr2]2Fe(CO)3 (n/Ar = 3/Ph 3, 4/Ph 4a, 4/p-tol 4b; 56-19%). Crystal structures establish essentially parallel P-Fe-P axes, iron-iron distances of 5.894(9)-5.782(1) Å (3) and 6.403(1)-6.466(1) Å (4a,b), and van der Waals radii of 4.45 Å for the Fe(CO)3 rotators, the planes of which are offset by 0.029-1.665 Å. Analogous reactions of Ph2P(CH2)6PPh2 yield the square pyramidal monoiron complex trans-(CO)3Fe[Ph2P(CH2)6PPh2] (6', 31%), a rare case where a diphosphine spans trans basal positions (∠P-Fe-P 147.4(2)°). Both 3 and 6' exhibit two CO 13C NMR signals at room temperature, indicating slow exchange on the NMR time scale, which in the former could entail Fe(CO)3/Fe(CO)3 gearing. Under analogous conditions, 4a,b exhibit one signal. Previously reported adducts of Fe(CO)3 and Ph2P(CH2)nPPh2 are surveyed (1:1, n = 1-5; 2:2, n = 5), and the IR νC≡O band patterns and energies of all complexes analyzed with the aid of DFT calculations. The diiron complexes are preferred thermodynamically. Attention is given to limiting types of Fe(CO)3/Fe(CO)3 interactions in the diiron complexes.

An amber obligate active site-directed ligand evolution technique for phage display.

Although noncanonical amino acids (ncAAs) were first incorporated into phage libraries through amber suppression nearly two decades ago, their application for use in drug discovery has been limited due to inherent library bias towards sense-containing phages. Here, we report a technique based on superinfection immunity of phages to enrich amber-containing clones, thus avoiding the observed bias that has hindered incorporation of ncAAs into phage libraries. We then take advantage of this technique for development of active site-directed ligand evolution of peptides, where the ncAA serves as an anchor to direct the binding of its peptides to the target's active site. To demonstrate this, phage-displayed peptide libraries are developed that contain a genetically encoded butyryl lysine and are subsequently used to select for ligands that bind SIRT2. These ligands are then modified to develop low nanomolar inhibitors of SIRT2.

Supramolecular Metallacycles and Their Binding of Fullerenes.

The synthesis of a new triaminoguanidinium-based ligand with three tris-chelating [NNO]-binding pockets and C3 symmetry is described. The reaction of tris-(2-pyridinylene-N-oxide)triaminoguanidinium salts with zinc(II) formate leads to the formation of cyclic supramolecular coordination compounds which in solution bind fullerenes in their spherical cavities. The rapid encapsulation of C60 can be observed by NMR spectroscopy and single-crystal X-ray diffraction and is verified using computation.

Ethylene-Bridged Hexadentate Bis(amidines) and Bis(amidinates) with Variable Binding Sites.

Hexadentate bis(amidines) form versatile networks of hydrogen bonds both in solid state and solution, as revealed by X-ray crystallography, IR, and NMR spectroscopy. Moreover, the corresponding bis(amidinates) produce blue and green emissions in THF solution. Tethered tetradentate bis(amidines) have emerged in coordination chemistry, enantioselective catalysis, as building blocks for polyfunctional heterocycles, and in photoluminescent materials. The next generation of flexible bis(amidine)/bis(amidinate) platforms with up to six N-donor sites has now been established.

From One-Pot NH-Sulfoximidations of Thiophene Derivatives to Dithienylethene-Type Photoswitches.

Thiophene NH-sulfoximines have been synthesized using a one-pot NH-sulfoximidation reaction of thiophenes. The reactivity of the products was investigated, and the developed protocols were used for the synthesis of a new class of dithienylethene-type photoswitches containing a sulfoximidoyl group.

Origin of Shielding and Deshielding Effects in NMR Spectra of Organic Conjugated Polyynes.

Nucleus independent chemical shifts (NICS) for conjugated polyynes H(C≡C) nH are reported ( n = 2-10). There is marked shielding within the carbon chain, gradually decreasing with radial distance and transitioning to a weakly deshielding region at 2.5-3.0 Å, as well as other trends. Interestingly, the magnitude of the shielding is only very weakly dependent upon the chain length or distance from the termini. 1H and 13C NMR chemical shifts are also computed and the trends analyzed.

Three-Fold Intramolecular Ring Closing Alkene Metatheses of Square Planar Complexes with cis Phosphorus Donor Ligands P(X(CH2) mCH═CH2)3 (X = -, m = 5-10; X = O, m = 3-5): Syntheses, Structures, and Thermal Properties of Macrocyclic Dibridgehead Diphosphorus Complexes.

Reactions of cis-PtCl2(P((CH2) mCH═CH2)3)2 and Grubbs' first generation catalyst and then hydrogenations afford cis- PtCl2(P((CH2) n)3 P) ( cis-2; n = 2 m + 2 = 12 (b), 14 (c), 16 (d), 18 (e), 20 (f), 22 (g); 6-40%), derived from 3-fold interligand metatheses. The phosphite complexes cis-PtCl2(P(O(CH2) m*CH═CH2)3)2 are similarly converted to cis- PtCl2(P(O(CH2) n*O)3 P) ( cis-5; n* = 8 (a), 10 (b), 12 (c), 10-20%). The substitution products cis- PtPh2(P((CH2) n)3 P) ( cis-6c,d) and cis- PtI2(P(O(CH2)10O)3 P) are prepared using Ph2Zn and NaI, respectively. Crystal structures of cis-2c,d,f, cis-5a,b, and cis-6c show one methylene bridge that roughly lies in the platinum coordination plane and two that are perpendicular. The thermal behavior of the complexes is examined. When the bridges are sufficiently long, they rapidly exchange via an unusual "triple jump rope" motion over the PtX2 moieties. NMR data establish Δ H⧧, Δ S⧧, and Δ G298K⧧/Δ G393K⧧ values of 7.8 kcal/mol, -27.9 eu, and 16.1/18.8 kcal/mol for cis-2d, and a Δ G393K⧧ of ≥19.6 kcal/mol for the shorter bridged cis-2c. While cis-2c,g gradually convert to trans-2c,g at 150-185 °C in haloarenes, trans-2c,g give little reaction under analogous conditions, establishing the stability order trans > cis. Similar metathesis/hydrogenation sequences with octahedral complexes containing two cis phosphine ligands, fac-ReX(CO)3(P((CH2)6CH═CH2)3)2 (X = Cl, Br), give fac- ReX(CO)3( P(CH2)13 CH2)((CH2)14)( P(CH2)13 CH2) (19-50%), which are derived from a combination of interligand and intraligand metathesis. The relative stabilities of cis/ trans and other types of isomers are probed by combinations of molecular dynamics and DFT calculations.

tRNAPyl: Structure, function, and applications.

Pyrrolysine is the 22nd proteinogenic amino acid encoded into proteins in response to amber (TAG) codons in a small number of archaea and bacteria. The incorporation of pyrrolysine is facilitated by a specialized aminoacyl-tRNA synthetase (PylRS) and its cognate tRNA (tRNAPyl). The secondary structure of tRNAPyl contains several unique features not found in canonical tRNAs. Numerous studies have demonstrated that the PylRS/tRNAPyl pair from archaea is orthogonal in E. coli and eukaryotic hosts, which has led to the widespread use of this pair for the genetic incorporation of non-canonical amino acids. In this brief review we examine the work that has been done to elucidate the structure of tRNAPyl, its interaction with PylRS, and survey recent progress on the use of tRNAPyl as a tool for genetic code expansion.

Syntheses, structures, and stabilities of aliphatic and aromatic fluorous iodine(I) and iodine(III) compounds: the role of iodine Lewis basicity.

The title molecules are sought in connection with various synthetic applications. The aliphatic fluorous alcohols Rfn CH2OH (Rfn = CF3(CF2) n-1; n = 11, 13, 15) are converted to the triflates Rfn CH2OTf (Tf2O, pyridine; 22-61%) and then to Rfn CH2I (NaI, acetone; 58-69%). Subsequent reactions with NaOCl/HCl give iodine(III) dichlorides Rfn CH2ICl2 (n = 11, 13; 33-81%), which slowly evolve Cl2. The ethereal fluorous alcohols CF3CF2CF2O(CF(CF3)CF2O) x CF(CF3)CH2OH (x = 2-5) are similarly converted to triflates and then to iodides, but efforts to generate the corresponding dichlorides fail. Substrates lacking a methylene group, Rfn I, are also inert, but additions of TMSCl to bis(trifluoroacetates) Rfn I(OCOCF3)2 appear to generate Rfn ICl2, which rapidly evolve Cl2. The aromatic fluorous iodides 1,3-Rf6C6H4I, 1,4-Rf6C6H4I, and 1,3-Rf10C6H4I are prepared from the corresponding diiodides, copper, and Rfn I (110-130 °C, 50-60%), and afford quite stable Rfn C6H4ICl2 species upon reaction with NaOCl/HCl (80-89%). Iodinations of 1,3-(Rf6)2C6H4 and 1,3-(Rf8CH2CH2)2C6H4 (NIS or I2/H5IO6) give 1,3,5-(Rf6)2C6H3I and 1,2,4-(Rf8CH2CH2)2C6H3I (77-93%). The former, the crystal structure of which is determined, reacts with Cl2 to give a 75:25 ArICl2/ArI mixture, but partial Cl2 evolution occurs upon work-up. The latter gives the easily isolated dichloride 1,2,4-(Rf8CH2CH2)2C6H3ICl2 (89%). The relative thermodynamic ease of dichlorination of these and other iodine(I) compounds is probed by DFT calculations.

Octahedral Werner complexes with substituted ethylenediamine ligands: a stereochemical primer for a historic series of compounds now emerging as a modern family of catalysts.

As reported by Alfred Werner in 1911-1912, salts of the formally D3 symmetric [Co(en)3]3+ (en = ethylenediamine) trication were among the first chiral inorganic compounds to be resolved into enantiomers, the absolute configurations of which are denoted Λ (left handed helix) or Δ (right handed helix). After a >100 year dormant period during which few useful reactions of these substitution inert complexes were described, carbon substituted derivatives have recently been found to be potent catalysts for enantioselective organic synthesis. This review systematically outlines the fascinating range of stereoisomers that can arise, such as conformers associated with the five membered chelate rings (λ/δ), alignment modes of the C-C bonds with the C3 symmetry axis (lel/ob), geometric isomers (fac/mer), and configurational diastereomers (R/S) arising from carbon stereocenters. These analyses demonstrate a profound stereochemical diversity that can be applied in catalyst optimization. Efforts are made to bridge the often orthogonal nomenclature systems inorganic and organic chemists employ to describe these phenomena.

Ruthenium(II) arene complexes with chelating chloroquine analogue ligands: synthesis, characterization and in vitro antimalarial activity.

Three new ruthenium complexes with bidentate chloroquine analogue ligands, [Ru(η(6)-cym)(L(1))Cl]Cl (1, cym = p-cymene, L(1) = N-(2-((pyridin-2-yl)methylamino)ethyl)-7-chloroquinolin-4-amine), [Ru(η(6)-cym)(L(2))Cl]Cl (2, L(2) = N-(2-((1-methyl-1H-imidazol-2-yl)methylamino)ethyl)-7-chloroquinolin-4-amine) and [Ru(η(6)-cym)(L(3))Cl] (3, L(3) = N-(2-((2-hydroxyphenyl)methylimino)ethyl)-7-chloroquinolin-4-amine) have been synthesized and characterized. In addition, the X-ray crystal structure of 2 is reported. The antimalarial activity of complexes 1-3 and ligands L(1), L(2) and L(3), as well as the compound N-(2-(bis((pyridin-2-yl)methyl)amino)ethyl)-7-chloroquinolin-4-amine (L(4)), against chloroquine sensitive and chloroquine resistant Plasmodium falciparum malaria strains was evaluated. While 1 and 2 are less active than the corresponding ligands, 3 exhibits high antimalarial activity. The chloroquine analogue L(2) also shows good activity against both the chloroquine sensitive and the chloroquine resistant strains. Heme aggregation inhibition activity (HAIA) at an aqueous buffer/n-octanol interface (HAIR(50)) and lipophilicity (D, as measured by water/n-octanol distribution coefficients) have been measured for all ligands and metal complexes. A direct correlation between the D and HAIR(50) properties cannot be made because of the relative structural diversity of the complexes, but it may be noted that these properties are enhanced upon complexation of the inactive ligand L(3) to ruthenium, to give a metal complex (3) with promising antimalarial activity.