N-Heterocyclic carbenes (NHCs) are known to stabilize some metal atoms in different oxidation states mostly by their strong σ-donation. After the successful syntheses of cyclic alkyl(amino) carbenes (cAACs), they have been proven to be much more effective in stabilizing electron rich species. In cAAC, one of the σ-withdrawing and π-donating nitrogen atoms of NHC is replaced by a σ-donating quaternary carbon atom leading to a lower lying LUMO. This makes the acceptance of π-back-donation from the element bound to the carbene carbon atom of cAAC energetically more advantageous. Further evidence suggests that the carbene carbon of cAAC can use the lone pair of electrons present on the adjacent nitrogen in a more controlled way depending on the accumulation of electron density on the bound metal. It has been found that cAAC can be utilized as excellent ligand for the stabilization of a complex with three coordinate metal center [(cAAC)2M(I)-Cl; M = Fe, Co, Cr]. Complex (cAAC)2M(II)Cl2 [M = Fe, Co, Cr] was prepared by reacting anhydrous M(II)Cl2 with two equiv of cAAC followed by treatment with one equiv of KC8 (reducing agent) to obtain (cAAC)2M(I)-Cl. The corresponding cation (cAAC)2M(+) was isolated when (cAAC)2M(I)-Cl was reacted with sodium-tetraarylborate (lithium) in toluene or fluorobenzene. The CV of cation (cAAC)2M(+) [M = Co, Fe] suggests that it can reversibly undergo one electron reduction. The cations of Co and Fe were reduced with Na(Hg) or KC8, respectively. (cAAC)2Co(I)Cl can be directly reduced to (cAAC)2Co(0) when reacted with one equiv of KC8. Analogous (cAAC·)2Zn(II) and (cAAC)2Mn complexes are prepared by reduction of (cAAC)MCl2 [M = Zn, Mn] with two equiv of KC8 in the presence of one equiv of cAAC. The square planar (cAAC)2NiCl2 complex was directly reduced by two equiv of LiN(iPr2) (KC8) to (cAAC)2Ni(0). The (cAAC)2Pd(0) and (cAAC)2Pt(0) complexes are prepared by substituting all four triphenylphosphines of (Ph3P)4M(0) [M = Pd, Pt] by two cAACs. Cation (cAAC)2M(+) [M = Cu, Au] was reduced with sodium/potassium to obtain the neutral analogue [(cAAC)2Cu, (cAAC)2Au]. Two coordinate Zn/Mn/Cu/Au are stabilized by two neutral carbene ligands possessing radical electrons on the carbene carbon atoms, while analogous complexes of Co/Fe/Ni/Pd/Pt contain metals in the zero oxidation state. The ground electronic structure of (cAAC)2M was thoroughly studied by theoretical calculations. In this Account, we summarize our developments in stabilizing metal complexes with low coordinate metal atoms in two, one, and most significantly in their zero oxidation states by utilizing cAACs as ligands.

Dengue is a vector-borne viral disease, caused by the Flavivirus, Dengue virus (DENV). About 400 million cases and 22000 deaths occur due to dengue throughout the world each year. It is reported in more than 100 countries in the tropics and subtropical regions. A positive-stranded enveloped RNA virus, DENV is principally transmitted by Aedes mosquitoes. It has four antigenically distinct serotypes DENV-1 to 4, with different genotypes, having three structural proteins and seven non-structural proteins. Clinical symptoms of dengue range from mild fever to severe Dengue Haemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS), with thrombocytopenia, leucopenia, and increased vascular permeability. Though primary infection causes activation of immune responses against that DENV serotypes, the severity of the disease in enhanced via heterotypic infection by various serotypes and also by antibody dependent enhancement (ADE). The first licensed DENV vaccine was tetravalent CYD Denvaxia, but it was not approved in all countries. Lack of suitable animal model, proper mechanistic study in pathogenesis and ADE, are the main hindrances in vaccine development. This review summarizes the current knowledge on DENV epidemiology, biology, disease etiology in the context of prevention and protection from dengue virus disease.

The cyclic alkyl(amino) carbene (cAAC) bonded chlorophosphinidene (cAAC)PÀCl (2/2')w as isolated from the direct reaction between cAAC and phosphorus trichloride (PCl 3 ). Compound 2/2' has been characterizedb y NMR spectroscopy and mass spectrometry. 31 PNMR investigations [d % 160 ppm (major) and d % 130 ppm (minor)] reveal that there are two different Pe nvironments of the PÀCl unit. X-ray single-crystal determinations uggests ac o-crystallization of two conformational isomers of (cAAC)PÀCl (2/2'); the major compound possessing ac AACÀPCl unit with C cAAC ÀP1 .75 .T his CÀPb ond length is very close to that of (NHC) 2 P 2 [NHC = N-heterocyclic carbene].T he residual density can be interpreted as ac onformational isomer with as horter C cAAC ÀPb ond similar to an on-conjugated phosphaalkene [RÀP=CR 2 ]. Our study shows an unprecedented example of two conformational isomersw ith different C carbene Àelementb onds. Additionally,B r( 3c/3c'), I( 4c/4c'), and H( 5c/5c')a nalogues [(Me 2 -cAAC)PÀX; X= Br (3), I( 4), H( 5)] of 2c/2c'[(Me 2 -cAAC)PÀCl] were also synthesized and characterized by NMR spectroscopy suggesting similare quilibrium in solution. The unique property of cAAC and the required electronegativity of the X( X= Cl, Br,I ,a nd H) atom play ac rucial role for the existence of the two isomersw hichw ere further studied by theoretical calculations.Since the synthetic reports of stable and isolable singlet Nheterocyclic carbenes (NHCs) in 1988 by Bertrand et al. [1] and in 1991 by Arduengo et al., [2] syntheses and characterization of severals table carbenes have been reported. [3] The use of carbenes has brought numerousb reakthroughs in the field of homogenous catalysis [4] and NHCs have been utilized as strong s-donors in different fields of chemistry. [5] The carbene carbon atom of an NHC is bound to two s-withdrawing and p-donating nitrogen atoms. [5] Consequently,t he accumulationo fe lectron density in the p z -orbital of the carbenec arbon atom is reasonably high leading to the weak p-accepting property of NHC. [6] Theoretical studies as well as experimental evidence have shown that non-negligible p-back-donation occurs in the bondingb etween NHCs and transition metals. [7] The syntheses of cyclic alkyl(amino)c arbenes (cAACs) [8] were reported in 2005 by Bertrande tal. One s-withdrawing and p-donating nitrogen atom of an NHC is replaced by a s-donating quaternary carbon atom in cAAC leading to al ower lying LUMO. cAACs are superior ligands for the stabilization of various unstable chemicals pecies, [9] radicals, [10] and elements in their different oxidation states [11] due to their stronger p-accepting properties. This is energetically advantageous for acceptance of pback donation from the element bound to the carbene carbon atom (C cAAC )o fc AAC (see the Supporting Information). [3b, 12, 13] The electronic properties of C cAAC and the accumulation of electron densities on the elements (E) are very important since they control the chemical behavior of the cAAC-containing compo...

The bisadduct (cAAC)2NiIICl2 [1; cAAC = cyclic (alkyl)(amino)carbene] was directly synthesized by treating cAAC with NiCl2. Compound 1 was reduced to (cAAC)2Ni0 (2) by using lithium diisopropylamide or KC8. Crystals of 2 were stable under an inert gas for several months and decomposed upon heating above 165 °C. On the basis of the calculated natural bond orbital charge values of the nickel atom in 2, the oxidation state of nickel was determined to be between NiI and Ni0 (+0.34). Theoretical calculations suggested a closed‐shell singlet electronic configuration of 2 with little biradical character. Ab initio multiconfigurational C(R)ASSCF/CASPT2 calculations predicted a closed‐shell singlet electronic configuration (Ni0), whereas excited spin states possessed NiI character with unpaired electrons on neighboring carbon atoms. The catalytic activity of complex 2 was investigated for the homocoupling of various unactivated aryl chlorides/fluorides. The biaryls were obtained in good yields at moderate temperature. Theoretical studies showed that an intermediate containing NiIII was more favored than one with NiIV.

Reduction of the neutral carbene tetrachlorosilane adduct (cAAC)SiCl4 (cAAC=cyclic alkyl(amino) carbene :C(CMe2)2 (CH2)N(2,6-iPr2C6H3) with potassium graphite produces stable (cAAC)3Si3, a carbene-stabilized triatomic silicon(0) molecule. The Si-Si bond lengths in (cAAC)3Si3 are 2.399(8), 2.369(8) and 2.398(8) Å, which are in the range of Si-Si single bonds. Each trigonal pyramidal silicon atom of the triangular molecule (cAAC)3Si3 possesses a lone pair of electrons. Its bonding, stability, and electron density distributions were studied by quantum chemical calculations.

Compound (Me2 -cAAC:)2 Co(0) (2; Me2 -cAAC:=cyclic (alkyl) amino carbene; :C(CH2 )(CMe2 )2 N-2,6-iPr2 C6 H3 ) was synthesized by the reduction of the precursor (Me2 -cAAC:)2 Co(I) Cl (1) with KC8 in THF. The cyclic voltammogram of 1 exhibited one-electron reduction, which suggests that synthesis of a bent 2-metallaallene (2) from 1 should be possible. Compound 2 contains one cobalt atom in the formal oxidation state zero, which is stabilized by two Me2 -cAAC: ligands. Bond lengths from X-ray diffraction are 1.871(2) and 1.877(2) Å with a C-Co-C bond angle of 170.12(8)°. The EPR spectrum of 2 exhibited a broad resonance attributed to the unique quasi-linear structure, which favors near degeneracy and gives rise to very rapid relaxation conditions. The cAACCo bond in 2 can be considered as a typical Dewar-Chatt-Duncanson type of bonding, which in turn retains 2.5 electron pairs on the Co atom as nonbonding electrons.

Uracil-DNA glycosylase (UDG), a key highly conserved DNA repair enzyme involved in uracil excision repair, was discovered in Escherichia coli . The Bacillus subtilis bacteriophage, PBS-1 and PBS-2, which contain dUMP residues in their DNA, express a UDG inhibitor protein, Ugi which binds to UDG very tightly to form a physiologically irreversible complex. The X-ray analysis of the E. coli UDG ( Ec UDG)-Ugi complex at 3.2 A resolution, leads to the first structure elucidation of a bacterial UDG molecule. This structure is similar to the enzymes from human and viral sources. A comparison of the available structures involving UDG permits the delineation of the constant and the variable regions of the molecule. Structural comparison and mutational analysis also indicate that the mode of action of the enzyme from these sources are the same. The crystal structure shows a remarkable spatial conservation of the active site residues involved in DNA binding in spite of significant differences in the structure of the enzyme-inhibitor complex, in comparison with those from the mammalian and viral sources. Ec UDG could serve as a prototype for UDGs from pathogenic prokaryotes, and provide a framework for possible drug development against such pathogens with emphasis on features of the molecule that differ from those in the human enzyme.

Radicals are an important class of species which act as intermediates in numerous chemical and biological processes. Most of the radicals have short lifetimes. However, radicals with longer lifetimes can be isolated and stored in a pure form. They are called stable radicals. Over the last five decades, the syntheses of several stable radicals have been reported. Recently, highly unstable radicals have been successfully stabilized via strong σ-donation of singlet carbenes. Cyclic aklyl(amino) carbene (cAAC) is regarded as a stronger σ-donor and a better π-acceptor when compared with that of an N-heterocyclic carbene (NHC). In this article we review preferentially the results of our group to generate stable radical centers on the carbene carbon atoms by employing the so far hidden and unique ability of the cAACs. We focus on the development of new synthetic routes to stable and isolable radicals containing silicon atoms. All the compounds have been well characterized by single crystal X-ray analysis; the mono-radicals have been distinguished by EPR spectroscpy and the ground state of the diradicals has been studied by magnetic susceptibility measurements and theoretical calculations. Many of these compounds are studied by cyclic voltammetry and are often converted to their corresponding radical cations or radical anions via electron abstraction or addition processes. Some of them are stable, having long lifetimes and hence are isolated and characterized thoroughly. Not much information has been obtained on the short lived persistent radical species. Herein, we discuss some of the examples of such a type of species and focus on what kind of chemical reactions are initiated by these short-lived radical species in solution. We also briefly mention the syntheses and charaterization of the so far reported stable silicon centered radicals.