Rare Tautomers of Artificially Expanded Genetic Letters and their Effects on the Base Pair Stabilities

In order to expand the existing genetic letters, it is necessary to design robust nucleotides that can function naturally in living cells. Therefore, it is desirable to examine the roles of recently-proposed second-generation artificially genetic letters in producing stable duplex DNA. Herein, a reliable dispersion-corrected density functional theory method is used to shed light on the electronic structures and properties of different rare tautomers of proposed expanded genetic letters and their effects on the base pair stabilities in the duplex DNA. It is found that the rare tautomers are not only stable in the aqueous medium but can also pair with natural bases to produce stable mispairs. Except for J and V, all of the artificial genetic letters are found to produce mispairs that are about 1–7 kcal mol⁻¹ more stable than their complementary counterparts. They are also appreciably more stable than the naturally occurring G : C, A : T, and G : T pairs. Mainly attractive electrostatic interactions and polarity of the monomers are responsible for the higher base pair stabilities.     

PtII Coordination to N1 of 9‐Methylguanine: Why it Facilitates Binding of Additional Metal Ions to the Purine Ring

The preparation and X‐ray crystal structure analysis of {trans‐[Pt(MeNH₂)₂(9‐MeG‐N1)₂]} ? {3 K₂[Pt(CN)₄]} ? 6 H₂O ( 3 a ) (with 9‐MeG being the anion of 9‐methylguanine, 9‐MeGH) are reported. The title compound was obtained by treating [Pt(dien)(9‐MeGH‐N7)]²⁺ ( 1 ; dien=diethylenetriamine) with trans‐[Pt(MeNH₂)₂(H₂O)₂]²⁺ at pH 9.6, 60 °C, and subsequent removal of the [(dien)Pt^II] entities by treatment with an excess amount of KCN, which converts the latter to [Pt(CN)₄]^2?. Cocrystallization of K₂[Pt(CN)₄] with trans‐[Pt(MeNH₂)₂(9‐MeG‐N1)₂] is a consequence of the increase in basicity of the guanine ligand following its deprotonation and Pt coordination at N1. This increase in basicity is reflected in the pK_a values of trans‐[Pt(MeNH₂)₂(9‐MeGH‐N1)₂]²⁺ (4.4±0.1 and 3.3±0.4). The crystal structure of 3 a reveals rare (N7,O6 chelate) and unconventional (N2,C2,N3) binding patterns of K⁺ to the guaninato ligands. DFT calculations confirm that K⁺ binding to the sugar edge of guanine for a N1‐platinated guanine anion is a realistic option, thus ruling against a simple packing effect in the solid‐state structure of 3 a . The linkage isomer of 3 a , trans‐[Pt(MeNH₂)₂(9‐MeG‐N7)₂] ( 6 a ) has likewise been isolated, and its acid–base properties determined. Compound 6 a is more basic than 3 a by more than 4 log units. Binding of metal entities to the N7 positions of 9‐MeG in 3 a has been studied in detail for [(NH₃)₃Pt^II], trans‐[(NH₃)₂Pt^II], and [(en)Pd^II] (en=ethylenediamine) by using ¹H NMR spectroscopy. Without exception, binding of the second metal takes place at N7, but formation of a molecular guanine square with trans‐[(Me₂NH₂)Pt^II] cross‐linking N1 positions and trans‐[(NH₃)₂Pt^II] cross‐linking N7 positions could not be confirmed unambiguously, despite the fact that calculations are fully consistent with its existence.     

The Role of Substituent Effects in Tuning Metallophilic Interactions and Emission Energy of Bis‐4‐(2‐pyridyl)‐1,2,3‐triazolatoplatinum(II) Complexes

The photoluminescence spectra of a series of 5‐substituted pyridyl‐1,2,3‐triazolato Pt^II homoleptic complexes show weak emission tunability (ranging from λ=397–408 nm) in dilute (10^?6 M ) ethanolic solutions at the monomer level and strong tunability in concentrated solutions (10^?4 M ) and thin films (ranging from λ=487–625 nm) from dimeric excited states (excimers). The results of density functional calculations (PBE0) attribute this “turn‐on” sensitivity and intensity in the excimer to strong Pt–Pt metallophilic interactions and a change in the excited‐state character from singlet metal‐to‐ligand charge transfer (¹MLCT) to singlet metal‐metal‐to‐ligand charge transfer (¹MMLCT) emissions in agreement with lifetime measurements.     

Synthesis,Characterization, and Electro‐Optical Properties of ZnII Complexes with π‐Conjugated Terpyridine Ligands

Leading light : A series of zinc(II) bis‐terpyridine complexes (see picture) is investigated by means of DFT calculations combined with Bader's quantum theory of atoms in molecules. Raman spectroscopy experiments and studies of the electro‐optical properties of the complexes in solution and the solid state are also performed to examine their potential as new emissive materials in light‐emitting devices.

     

Ligand Design for Site‐Selective Metal Coordination: Synthesis of Transition‐Metal Complexes with η6‐Coordination of the Central Ring of Anthracene

A polycyclic aromatic ligand for site‐selective metal coordination was designed by using DFT calculations. The computational prediction was confirmed by experiments: 2,3,6,7‐tetramethoxy‐9,10‐dimethylanthracene initially reacts with [(C₅H₅)Ru(MeCN)₃]BF₄ to give the kinetic product with a [(C₅H₅)Ru]⁺ fragment coordinated at the terminal ring, which is then transformed into the thermodynamic product with coordination through the central ring. These isomeric complexes have markedly different UV/Vis spectra, which was explained by analysis of the frontier orbitals. At the same time, the calculations suggest that electrostatic interactions are mainly responsible for the site selectivity of the coordination.     

Synthesis,Coordination Chemistry and Bonding of Strong N‐Donor Ligands Incorporating the 1H‐Pyridin‐(2E)‐Ylidene (PYE) Motif

A range of N‐donor ligands based on the 1H‐pyridin‐(2E)‐ylidene (PYE) motif have been prepared, including achiral and chiral examples. The ligands incorporate one to three PYE groups that coordinate to a metal through the exocyclic nitrogen atom of each PYE moiety, and the resulting metal complexes have been characterised by methods including single‐crystal X‐ray diffraction and NMR spectroscopy to examine metal–ligand bonding and ligand dynamics. Upon coordination of a PYE ligand to a proton or metal‐complex fragment, the solid‐state structures, NMR spectroscopy and DFT studies indicate that charge redistribution occurs within the PYE heterocyclic ring to give a contribution from a pyridinium–amido‐type resonance structure. Additional IR spectroscopy and computational studies suggest that PYE ligands are strong donor ligands. NMR spectroscopy shows that for metal complexes there is restricted motion about the exocyclic C? N bond, which projects the heterocyclic N‐substituent in the vicinity of the metal atom causing restricted motion in chelating‐ligand derivatives. Solid‐state structures and DFT calculations also show significant steric congestion and secondary metal–ligand interactions between the metal and ligand C? H bonds.     

Reversible α‐Hydrogen and α‐Alkyl Elimination in PC(sp3)P Pincer Complexes of Iridium

Despite significant progress in recent years, the cleavage of unstrained C(sp³)? C(sp³) bonds remains challenging. A C? C coupling and cleavage reaction in a PC(sp³)P iridium pincer complex is mechanistically studied; the reaction proceeds via the formation of a carbene intermediate and can be described as a competition between α‐hydrogen and α‐alkyl elimination; the latter process was observed experimentally and is an unusual way of C(sp³)? C(sp³) bond scission, which has previously not been studied in detail. Mechanistic details that are based upon kinetic studies, activation parameters, and DFT calculations are also discussed. A full characterization of a C? C agostic intermediate is presented.     

Novel Platinum(II) Complexes with Dipyridyl Containing Chelating Ligands and their Products with the Model Nucleobases 1‐Methylthymine and 1‐Methyluracil

The reactions of [Pt(dpma)(H₂O)₂]²⁺ (dpma = 2,2′‐dipyridylmethylamine) and [Pt(dpk)(H₂O)₂]²⁺ (dpk = 2,2′‐dipyridylketone) with the model nucleobases 1‐methylthymine (1‐MeT) and 1‐methyluracil (1‐MeU) were studied. Reaction products were characterized by ¹⁹⁵Pt NMR spectroscopy and by X‐ray structure analysis. The symmetric dpma and dpk diaqua complexes form dinuclear complexes with 1‐methylthymine, acting as secondary bridging ligand via its N3 and O4 donor atoms. [Pt₂(dpma)₂(1‐MeT)₂](ClO₄)₂ · H₂O ( 5 ) and [Pt₂(dpk)(dpk · H₂O)(1‐MeT)₂](PF₆)₂ · 4 H₂O ( 6 ) both show a head‐to‐head arrangement. Biological tests show a significant in vitro antitumor activity of [Pt(dpk)Cl₂] against the human glioma cell line U 87.     

Bonding Analysis of N‐Heterocyclic Carbene Tautomers and Phosphine Ligands in Transition‐Metal Complexes: A Theoretical Study

DFT calculations at the BP86/TZ2P level were carried out to analyze quantitatively the metal–ligand bonding in transition‐metal complexes that contain imidazole (IMID), imidazol‐2‐ylidene (nNHC), or imidazol‐4‐ylidene (aNHC). The calculated complexes are [Cl₄TM(L)] (TM=Ti, Zr, Hf), [(CO)₅TM(L)] (TM=Cr, Mo, W), [(CO)₄TM(L)] (TM=Fe, Ru, Os), and [ClTM(L)] (TM=Cu, Ag, Au). The relative energies of the free ligands increase in the order IMID<nNHC<aNHC. The energy levels of the carbon σ lone‐pair orbitals suggest the trend aNHC>nNHC>IMID for the donor strength, which is in agreement with the progression of the metal–ligand bond‐dissociation energy (BDE) for the three ligands for all metals of Groups 4, 6, 8, and 10. The electrostatic attraction can also be decisive in determining trends in ligand–metal bond strength. The comparison of the results of energy decomposition analysis for the Group 6 complexes [(CO)₅TM(L)] (L=nNHC, aNHC, IMID) with phosphine complexes (L=PMe₃ and PCl₃) shows that the phosphine ligands are weaker σ donors and better π acceptors than the NHC tautomers nNHC, aNHC, and IMID.     

Intramolecular Gas‐Phase Reactions of Synthetic Nonheme Oxoiron(IV) Ions: Proximity and Spin‐State Reactivity Rules

The intramolecular gas‐phase reactivity of four oxoiron(IV) complexes supported by tetradentate N₄ ligands ( L ) has been studied by means of tandem mass spectrometry measurements in which the gas‐phase ions [Fe^IV(O)( L )(OTf)]⁺ (OTf=trifluoromethanesulfonate) and [Fe^IV(O)( L )]²⁺ were isolated and then allowed to fragment by collision‐induced decay (CID). CID fragmentation of cations derived from oxoiron(IV) complexes of 1,4,8,11‐tetramethyl‐1,4,8,11‐tetraazacyclotetradecane (tmc) and N,N′‐bis(2‐pyridylmethyl)‐1,5‐diazacyclooctane ( L ⁸Py₂) afforded the same predominant products irrespective of whether they were hexacoordinate or pentacoordinate. These products resulted from the loss of water by dehydrogenation of ethylene or propylene linkers on the tetradentate ligand. In contrast, CID fragmentation of ions derived from oxoiron(IV) complexes of linear tetradentate ligands N,N′‐bis(2‐pyridylmethyl)‐1,2‐diaminoethane (bpmen) and N,N′‐bis(2‐pyridylmethyl)‐1,3‐diaminopropane (bpmpn) showed predominant oxidative N‐dealkylation for the hexacoordinate [Fe^IV(O)( L )(OTf)]⁺ cations and predominant dehydrogenation of the diaminoethane/propane backbone for the pentacoordinate [Fe^IV(O)( L )]²⁺ cations. DFT calculations on [Fe^IV(O)(bpmen)] ions showed that the experimentally observed preference for oxidative N‐dealkylation versus dehydrogenation of the diaminoethane linker for the hexa‐ and pentacoordinate ions, respectively, is dictated by the proximity of the target C? H bond to the oxoiron(IV) moiety and the reactive spin state. Therefore, there must be a difference in ligand topology between the two ions. More importantly, despite the constraints on the geometries of the TS that prohibit the usual upright σ trajectory and prevent optimal σ_CH–σ* overlap, all the reactions still proceed preferentially on the quintet (S=2) state surface, which increases the number of exchange interactions in the d block of iron and leads thereby to exchange enhanced reactivity (EER). As such, EER is responsible for the dominance of the S=2 reactions for both hexa‐ and pentacoordinate complexes.     

Supramolecular Assembly of Metal Complexes by (Aryl)I⋅⋅⋅d [PtII] Halogen Bonds

The theoretical data for the half-lantern complexes [{Pt( )(μ- )}₂] [ 1 – 3 ; is cyclometalated 2-Ph-benzothiazole; is 2-SH-pyridine ( 1 ), 2-SH-benzoxazole ( 2 ), 2-SH-tetrafluorobenzothiazole ( 3 )] indicate that the Pt ⋅⋅⋅ Pt orbital interaction increases the nucleophilicity of the outer d orbitals to provide assembly with electrophilic species. Complexes 1 – 3 were co-crystallized with bifunctional halogen bonding (XB) donors to give adducts ( 1 – 3 )₂ ⋅ (1,4-diiodotetrafluorobenzene) and infinite polymeric [ 1⋅ 1,1′-diiodoperfluorodiphenyl]_n. X-ray crystallography revealed that the supramolecular assembly is achieved through (Aryl)I ⋅⋅⋅ d [Pt^II] XBs between iodine σ-holes and lone pairs of the positively charged (Pt^II)₂ centers acting as nucleophilic sites. The polymer includes a curved linear chain ⋅⋅⋅ Pt₂ ⋅⋅⋅ I(arene^F)I ⋅⋅⋅ Pt₂ ⋅⋅⋅ involving XB between iodine atoms of the perfluoroarene linkers and (Pt^II)₂ moieties. The ¹⁹⁵Pt NMR, UV/Vis, and CV studies indicate that XB is preserved in CH(D)₂Cl₂ solutions.     

Studies on [PtCl2]‐ or [AuCl]‐Catalyzed Cyclization of 1‐(Indol‐2‐yl)‐2,3‐Allenols: The Effects of Water/Steric Hindrance and 1,2‐Migration Selectivity

The [PtCl₂]‐ or [AuCl]‐catalyzed reaction of 1‐(indol‐2‐yl)‐2,3‐allenols occurred smoothly at room temperature to afford a series of poly‐substituted carbazoles efficiently. Compared with the [PtCl₂]‐catalyzed process, the [AuCl]‐catalyzed reaction represents a significant advance in terms of the scope and the selectivity. Selective 1,2‐alkyl or aryl migration of the gold carbene intermediate was observed: compared with the methyl group, the isopropyl, cyclopropyl, cyclobutyl, and cyclohexyl groups migrate exclusively; the cyclopropyl group shifts selectively over the ethyl group; the 1,2‐migration of a non‐methyl linear alkyl is faster than methyl group; the phenyl group migrates exclusively over methyl or ethyl group. DFT calculations show that water makes the elimination of H₂O facile requiring a much lower energy and validates the migratory preferences of different alkyl or phenyl groups observed.     

Triangular Nickel Complexes Derived from 2‐Pyridylcyanoxime: An Approach to the Magnetic Properties of the [Ni3(μ3‐OH){pyC(R)NO}3]2+ Core

A series of nickel complexes with nuclearity ranging from Ni₃ to Ni₆ have been obtained by treatment of a variety of nickel salts with the 2‐pyridylcyanoxime ligand. The reported compounds have as a common structural feature the triangular arrangement of nickel cations bridged by a central μ₃‐oxo/alkoxo ligand. These compounds are simultaneously the first nickel derivatives of the 2‐pyridylcyanoxime ligand and the first examples of isolated, μ₃‐O triangular pyridyloximate nickel complexes. Magnetic measurements reveal antiferromagnetic interactions promoted by the μ₃‐O and oximato superexchange pathways and comparison of the experimental structural and magnetic data with DFT calculations give an in‐depth explanation of the factors that determine the magnetic interaction in this kind of system.     

Unsymmetrical Binding Modes of the HOPNO Inhibitor of Tyrosinase: From Model Complexes to the Enzyme

The deciphering of the binding mode of tyrosinase (Ty) inhibitors is essential to understand how to regulate the tyrosinase activity. In this paper, by combining experimental and theoretical methods, we studied an unsymmetrical tyrosinase functional model and its interaction with 2‐hydroxypyridine‐N‐oxide (HOPNO), a new and efficient competitive inhibitor for bacterial Ty. The tyrosinase model was a dinuclear copper complex bridged by a chelated ring with two different complexing arms (namely (bis(2‐ethylpyridyl)amino)methyl and (bis(2‐methylpyridyl)amino)methyl). The geometrical asymmetry of the complex induces an unsymmetrical binding of HOPNO. Comparisons have been made with the binding modes obtained on similar symmetrical complexes. Finally, by using quantum mechanics/molecular mechanics (QM/MM) calculations, we studied the binding mode in tyrosinase from a bacterial source. A new unsymmetrical binding mode was obtained, which was linked to the second coordination sphere of the enzyme.     

Design of Luminescent,Heteroleptic, Cyclometalated PtII and PtIV Complexes: Photophysics and Effects of the Cyclometalated Ligands

Neutral pentafluorophenyl benzoquinolinyl Pt^II [Pt(bzq)(HC^N−κN)(C₆F₅)] ( 1 a – g ) complexes, bearing nonmetalated N-heterocyclic HC^N ligands [HC^N=2,5-diphenyl-1,3,4-oxadiazole (Hoxd) a , 2-(2,4-difluorophenyl)pyridine (dfppy) b , 2-phenylbenzo[d]thiazole (pbt) c , 2-(4-bromophenyl)benzo[d]thiazole (Br-pbt) d , 2-phenylquinoline (pq) e , 2-thienylpyridine (thpy) f , 1-(2-pyridyl)pyrene (pypy) g ], and heteroleptic bis(cyclometalated) Pt^IV fac-[Pt(bzq)(C^N)(C₆F₅)Cl] ( 2 b – g , bzq: benzo[h]quinolinyl) derivatives, generated by oxidation of 1 b – g with PhICl₂, are reported. The oxidation reaction of 1 a evolved with formation of the bimetallic Pt^IV complex syn-[Pt(bzq)(C₆F₅)Cl(μ-OH)]₂ 3 . The crystal structures of 1 a,d,f , 2 b,d,e and 3 were corroborated by X-ray crystallography. A comparative study of the absorption and photoluminescence properties of the two series of complexes Pt^II ( 1 ) and Pt^IV ( 2 ), supported by time-dependent DFT calculations (TD-DFT), is presented. The low-lying transitions (absorption and emission) of Pt^II complexes 1 a – e [solution and polystyrene (PS) films] were assigned to the IL/MLCT mixture located on the cyclometalated Pt(bzq) unit, with minor IL′/ML′CT/LL′CT contributions involving the non-metalated ligand. Complex 1 g , bearing the more delocalized pyridyl pyrene (Hpypy) as an ancillary ligand, shows dual ¹ππ* and ³ππ* (Hpypy) emission in fluid CH₂Cl₂ and dual ³IL/³MLCT [Pt(bzq)] and [³ππ*, Hpypy] phosphorescence at 77 K. Upon oxidation, Pt^IV complexes 2 b – f display (solution, PS) ligand-based phosphorescence that arises from the bzq in 2 b (³LC) or from the second C^N ligand in 2 c – f (³L′C) with some ³LL′CT in 2 f . Despite metalation of the pyrenyl group, 2 g exhibits dual emission ¹ππ*/³ππ* located on the pypy chromophore.     

Zinc Complexes of Cyclodextrin‐bearing 8‐Hydroxyquinoline Ligands: A Comparative Study

The mounting evidence supporting the role of metal ions in several diseases has turned metal‐ion chelation therapy into a promising treatment strategy. The design of efficient metal‐binding ligands requires in‐depth knowledge of molecular structure and stability constants of the complexes formed. This paper presents an extensive overview on the stability of zinc(II) and copper(II) complexes of a series of cyclodextrin‐8‐hydroxyquinoline conjugates. In order to explain the differences observed in the stability constants between the metal complexes of the 6‐functionalized and 3‐functionalized cyclodextrin isomers, conformational analysis and DFT simulations were also performed. Molecular simulations allowed us to clarify the binding mode and to explain the differences in the stability constants of the metal complexes of these derivatives.