The Structure of N1‐Hydroxylophine N3‐Oxide (=1‐Hydroxy‐2,4,5‐ triphenyl‐1H‐imidazole 3‐Oxide) in the Solid State

The crystal structure of 1‐hydroxy‐2,4,5‐triphenyl‐1H‐imidazole 3‐oxide ( 1 ) has been determined from laboratory X‐ray powder‐diffraction data. The two independent molecules in the asymmetric unit form chains via O? H???O hydrogen bonds related by a twofold screw axis. One of the O???O distances is extremely short (2.32(1) and 2.43(1) Å). Solid‐state NMR spectroscopy (CPMAS) combined with calculation of absolute shieldings (GIAO/B3LYP/6‐31G*) allowed us to determine that the compound behaves as if the O? H???O hydrogen bond has the proton in the middle (single‐well potential), resulting in the near identity of both ¹⁵N‐NMR signals.     

Solid‐State and Solution Structural Studies of 4‐{[C(E)]‐1H‐Azol‐1‐ylimino)methyl}pyridin‐3‐ols

The new N‐salicylideneheteroarenamines 1 – 4 were prepared by reacting the biologically relevant 3‐hydroxy‐4‐pyridinecarboxaldehyde ( 5 ) with 1H‐imidazol‐1‐amine ( 6 ), 1H‐pyrazol‐1‐amine ( 7 ), 1H‐1,2,4‐triazol‐1‐amine ( 8 ), and 1H‐1,3,4‐triazol‐1‐amine ( 9 ). Solution ¹H‐, ¹³C‐, and ¹⁵N‐NMR were used to establish that the hydroxyimino form A is the predominant tautomer. A combination of ¹³C‐ and ¹⁵N‐CPMAS‐NMR with X‐ray crystallographic studies confirms that the same form is present in the solid state. The stabilities and H‐bond geometries of the different forms, tautomers and rotamers, are discussed by using B3LYP/6‐31G** calculations.     

Solid‐State NMR Characterization of Wilkinson’s Catalyst Immobilized in Mesoporous SBA‐3 Silica

The Wilkinson’s catalyst [RhCl(PPh₃)₃] has been immobilized inside the pores of amine functionalized mesoporous silica material SBA‐3 and The structure of the modified silica surface and the immobilized rhodium complex was determined by a combination of different solid‐state NMR methods. The successful modification of the silica surface was confirmed by ²⁹Si CP‐MAS NMR experiments. The presence of the T_n peaks confirms the successful functionalization of the support and shows the way of binding the organic groups to the surface of the mesopores. ³¹P‐³¹P J‐resolved 2D MAS NMR experiments were conducted in order to characterize the binding of the immobilized catalyst to the amine groups of the linkers attached to the silica surface. The pure catalyst exhibits a considerable ³¹P‐³¹P J‐coupling, well resolvable in 2D MAS NMR experiments. This J‐coupling was utilized to determine the binding mode of the catalyst to the linkers on the silica surface and the number of triphenylphosphine ligands that are replaced by coordination bonds to the amine groups. From the absence of any resolvable ³¹P‐³¹P J‐coupling in off‐magic‐angle‐spinning experiments, as well as slow‐spinning MAS experiments, it is concluded, that two triphenylphosphine ligands are replaced and that the catalyst is bonded to the silica surface through two linker molecules.     

Synthesis and antimicrobial activity of N‐substituted N′‐[6‐methyl‐2‐oxido‐1,3,2‐dioxaphosphinino(5,4‐b)pyridine‐2‐yl]ureas

N‐Substituted N′‐[6‐methyl‐2‐oxido‐1,3,2‐dioxaphosphinino(5,4,‐b)pyridine‐2‐yl]ureas have been accomplished by condensation of equimolar quantities of chlorides of various carbamidophosphoric acids ( 3 ) with 3‐hydroxyl‐6‐methyl‐2‐pyridinemethanol (lutidine diol) ( 4 ) in the presence of triethylamine in dry toluene–tetrahydrofuran (1:1) mixture at 45–50°C. Their structures were established by elemental analyses, IR, ¹H NMR, ¹³C NMR, and ³¹P NMR spectral data. Their antifungal and antibacterial activity is also evaluated. Most of these compounds exhibited moderate antimicrobial activity in the assays. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:509–512, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10181     

Alkyl‐Tethered Bis‐Phosphoryl Compounds with two 1,3,2‐Benzodiazaphosphorinone Units; Oxidation,Complexation, and X‐Ray Structure Analysis of Selected Compounds

The reaction of the bis‐chlorophosphines 1 a – 1 d with bis(2‐chloroethyl)amine hydrochloride in the presence of triethylamine and with various trimethylsilylamines led to a new class of bis‐phosphorus ligands 2 a – 2 c and 3 a – 3 g . ³¹P‐NMR studies suggested that the bis‐phosphorus ligands undergo rotation reactions about the alkyl bridge in polar solvents. Compounds 2 a – 2 c showed initially only one sharp singlet each in their ³¹P‐NMR spectra. After a few days at room temperature, two signals were observed. Similar results were observed for 3 a – 3 g . In the solid state, the two phosphorus atoms in 2 c are not equivalent, as was confirmed by the observation of two signals in the solid state ³¹P‐NMR spectrum. Oxidation reactions of 2 a – 2 c by the hydrogen peroxide‐urea 1 : 1 adduct (NH₂)₂C(:O) · H₂O₂ led to the formation of the corresponding phosphoryl compounds 4 a – 4 c . Reaction of 2 a and 3 a with Pt[COD]Cl₂ (COD = 1.5‐Cyclooctadiene) furnished the complexes 5 and 6 . The NMR spectra suggested that the two chlorine atoms are in cis position. X‐ray structure analyses were conducted for 2 a , which exhibits twofold symmetry; 2 c , which is linked into dimers by hydrogen bonds C–H…O; and 6 , confirming the cis configuration.     

Synthesis of Enantiomerically Pure 1,5,5‐Trideuterated cis‐ and trans‐2,4‐Dioxa‐3‐phosphadecalins. 31P‐NMR Evidence of Covalent‐Bond Formation and the Stereochemical Implications in the Course of the Inhibition of δ‐Chymotrypsin

The irreversible inhibition of δ‐chymotrypsin with the enantiomerically pure, P(3)‐axially and P(3)‐equatorially X‐substituted cis‐ and trans‐configurated 2,4‐dioxa‐3‐phospha(1,5,5‐²H₃)bicyclo[4.4.0]decane 3‐oxides (X=F, 2,4‐dinitrophenoxy) was monitored by ³¹P‐NMR spectroscopy. ¹H‐Correlated ³¹P{²H}‐NMR spectra enabled the direct observation of the vicinal coupling (³J) between the P‐atom of the inhibitor and the CH₂O moiety of Ser¹⁹⁵ (=‘Ser¹⁹⁵’(CH₂O)), thus establishing the covalent nature of the ‘Ser¹⁹⁵’(CH₂O? P) bond in the inhibited enzyme. The stereochemical course of the phosphorylation is dependent on the structure of the inhibitor, and neat inversion, both inversion and retention, as well as neat retention of the configuration at the P‐atom was found.     

Low‐Energy‐Barrier Proton Transfer Induced by Electron Attachment to the Guanine⋅⋅⋅Cytosine Base Pair

The photoelectron spectrum of the anion of the guanine ??? cytosine base apair (GC)^.? is recorded for the first time. The observed variation in the spectral peak‐height ratios with the source conditions suggests the presence of two or more anionic isomers. Two maxima of the broad bands in the photoelectron spectrum were measured at about 1.9 and about 2.6 eV. These values are very well reproduced by the vertical detachment energies of the B3LYP/6‐31++G(d,p) calculated low‐energy anionic structures, which are 1) the Watson–Crick base‐pair anion with proton transferred from N1 of guanine to N3 of cytosine, 2) its analogue in which the proton is transferred from N9 of guanine to N7 of guanine, and 3) the global minimum geometry, which is formed from the latter anion by rotation of guanine about the axis approximately defined by C2 of guanine and C4 of cytosine. Furthermore, a minor difference in the stabilities of the two lowest energy anions explains the experimentally observed source (temperature) dependence of the PES spectrum. A rational procedure, based on the chemistry involved in the formation of anionic dimers, which enables the low‐energy anions populated in the photoelectron spectrum to be identified is proposed. In contrast to the alternative combinatorial approach, which in the studied case would lead to carrying out quantum chemical calculations for 2000–2500 structures, the procedure described here reduces the computational problem to only 15 geometries.     

Polymorphism vs. Desmotropy: The Cases of 3‐Phenyl‐ and 5‐Phenyl‐ 1H‐pyrazoles and 3‐Phenyl‐1H‐indazole

Two desmotropes, 3‐phenyl‐1H‐pyrazole ( 1a ) and 5‐phenyl‐1H‐pyrazole ( 1b ) have been isolated and the conditions for their interconversion established. The X‐ray structure of 1b has been determined (a=10.862(1), b=5.7620(5), c=12.927(2) Å, β=111.435(2)°, space group P2₁/c), and both tautomers 1a and 1b were characterized by NMR in the solid state (¹³C‐ and ¹⁵N‐CPMAS). In the case of 3‐phenyl‐1H‐indazole ( 2a ), two concomitant polymorphs have been analyzed by X‐ray crystallography, and their NMR spectral properties were determined. The low‐melting‐point polymorph, at 106.7°, contains three molecules in the asymmetric unit (a=41.086(1), b=7.3860(2), c=23.391(1) Å, β=117.697(1)°, space group C2/c) and the high‐melting‐point one, 115.3°, six molecules (a=13.7818(4), b=13.7976(5), c=18.9445(5) Å, α=94.300(3), β=95.131(3), γ=119.428(3)°, space group P‐1). Here, too, it has been experimentally determined how to transform one form into the other. Density‐functional‐theory calculations at the B3LYP/6‐31G** level have been performed in both examples to rationalize the stability of the different tautomers.     

Probing the interaction of the potassium channel modulating KCNE1 in lipid bilayers via solid‐state NMR spectroscopy

KCNE1 is known to modulate the voltage‐gated potassium channel α subunit KCNQ1 to generate slowly activating potassium currents. This potassium channel is essential for the cardiac action potential that mediates a heartbeat as well as the potassium ion homeostasis in the inner ear. Therefore, it is important to know the structure and dynamics of KCNE1 to better understand its modulatory role. Previously, the Sanders group solved the three‐dimensional structure of KCNE1 in LMPG micelles, which yielded a better understanding of this KCNQ1/KCNE1 channel activity. However, research in the Lorigan group showed different structural properties of KCNE1 when incorporated into POPC/POPG lipid bilayers as opposed to LMPG micelles. It is hence necessary to study the structure of KCNE1 in a more native‐like environment such as multi‐lamellar vesicles. In this study, the dynamics of lipid bilayers upon incorporation of the membrane protein KCNE1 were investigated using ³¹P solid‐state nuclear magnetic resonance (NMR) spectroscopy. Specifically, the protein/lipid interaction was studied at varying molar ratios of protein to lipid content. The static ³¹P NMR and T₁ relaxation time were investigated. The ³¹P NMR powder spectra indicated significant perturbations of KCNE1 on the phospholipid headgroups of multi‐lamellar vesicles as shown from the changes in the ³¹P spectral line shape and the chemical shift anisotropy line width. ³¹P T₁ relaxation times were shown to be reversely proportional to the molar ratios of KCNE1 incorporated. The ³¹P NMR data clearly indicate that KCNE1 interacts with the membrane. Copyright © 2017 John Wiley & Sons, Ltd.     

One‐ and two‐dimensional NMR characterization of N‐vinyl‐2‐pyrrolidone/methyl acrylate copolymers

N‐vinyl‐2‐pyrrolidone/methyl acrylate (V/M) copolymers were prepared by free‐radical bulk polymerization using benzoyl peroxide as an initiator. The copolymer composition of these copolymers was calculated from ¹H NMR spectra. The radical reactivity ratios for N‐vinyl‐2‐pyrrolidone (V) and methyl acrylate (M) were r_V = 0.09, r_M = 0.44. These reactivity ratios for the copolymerization of V and M were determined using the Kelen–Tudos and nonlinear least‐squares error‐in‐variable methods. The ¹³C{¹H} and ¹H NMR spectra of these copolymers overlapped and were complex. The complete spectral assignment of the ¹³C and ¹H NMR spectra were done with distortionless enhancement by polarization transfer and two dimensional ¹³C‐¹H heteronuclear single quantum correlation spectroscopic experiments. The two‐dimensional ¹H‐¹H homonuclear total correlation spectroscopic NMR spectrum showed the various bond interactions, thus inferring the possible structure of the copolymers. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2225–2236, 2002     

One‐ and two‐dimensional NMR characterization of N‐vinyl‐2‐pyrrolidone/methyl acrylate copolymers

N‐vinyl‐2‐pyrrolidone/methyl acrylate (V/M) copolymers were prepared by free‐radical bulk polymerization using benzoyl peroxide as an initiator. The copolymer composition of these copolymers was calculated from ¹H NMR spectra. The radical reactivity ratios for N‐vinyl‐2‐pyrrolidone (V) and methyl acrylate (M) were r_V = 0.09, r_M = 0.44. These reactivity ratios for the copolymerization of V and M were determined using the Kelen–Tudos and nonlinear least‐squares error‐in‐variable methods. The ¹³C{¹H} and ¹H NMR spectra of these copolymers overlapped and were complex. The complete spectral assignment of the ¹³C and ¹H NMR spectra were done with distortionless enhancement by polarization transfer and two dimensional ¹³C‐¹H heteronuclear single quantum correlation spectroscopic experiments. The two‐dimensional ¹H‐¹H homonuclear total correlation spectroscopic NMR spectrum showed the various bond interactions, thus inferring the possible structure of the copolymers. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2225–2236, 2002     

On RNA Triplet Interactions: NMR Study of the Short Intramolecular Duplex Formed by r[GCAm1G‐p‐O(CH2CH2O)6‐p‐UGCC], Preliminary Communication

The flexible hexaethylene‐glycol linker enhances the stability of the duplex between the two tetranucleotides in compound 1 sufficiently to allow determination of the solution structure by NMR. At 4.8°, two of the three possible imino NH protons are detected as sharp signals and establish the presence of two G⋅C Watson‐Crick base pairs. Through assignment of all but one of the non‐labile protons and measurement of ¹H,¹H and ¹H,³¹P coupling constants, as well as NOEs of labile and non‐labile protons, it was possible for the first time to derive detailed structural information on such a short duplex. It forms an A‐type double helix over the full length, including the dangling nucleotides. Small variations of coupling constants and a broadening of the H−C(8) signal of m¹G4 indicate that the two nucleotides connected to the linker are conformationally slightly distorted and/or more flexible than the unlinked end of the duplex.     

1‐Phosphabicyclo[3.2.1]octane

1‐Phosphabicyclo[3.2.1]octanes 1‐Phosphabicyclo[3.2.1]octane has been obtained by free‐radical cyclization of (2‐vinyl‐4‐pentenyl)‐phosphane in the presence of AIBN. Another approach to 1‐phosphabicyclo[3.2.1]octanes involves free‐radical cyclization of 2‐methyl‐4‐(2‐propenyl)‐phospholane synthesized by the reaction of [2‐(2‐propenyl)‐4‐pentenyl]‐phosphane with KPH₂/[18]crown‐6 in THF. The bicyclic phosphanes are characterized by reactions with CS₂, selenium, sulfur, NO, CH₃I, and HSO₃F, respectively, structural and analytical data as well as ¹H, ¹³C, ³¹P, ⁷⁷Se NMR spectral measurements. The steric crowding of the phosphanes as complex ligands has been estimated from ³¹P–¹H coupling constants according to the Tolman model. The configuration of the methyl substituents as well as the conformation of the six‐membered ring were determined by NMR parameters (coupling constants, noe's) and proved by X‐ray crystal structure analysis.     

Synthesis and antimicrobial activity of N‐(substituted)‐N‐[1,2,4,8,10,11‐hexachloro‐6‐oxido‐12H‐dibenzo(d,g)(1,3,2)‐dioxaphosphocin‐6‐yl]ureas

Substituted dibenzo dioxaphosphocin‐6‐yl ureas were synthesized by reacting hexachlorophene (4) with different carbamidophosphoric acid dichlorides (3) in the presence of triethylamine in dry toluene at 45‐50 ^oC. Their IR, ¹H, ¹³C and ³¹P NMR spectral data is discussed. These compounds were found to possess good antimicrobial activity.     

Complete 1H, 13C, 19F and 31P NMR data assignment of CWC‐related chemicals N,N‐dialkyl‐P‐alkyl phosphonamidic fluorides

The complete multinuclear ¹H, ¹³C, ³¹P and ¹⁹F NMR data of symmetrically substituted amines containing N,N‐dialkyl‐P‐alkyl phosphonamidic fluorides are presented. Assignment was achieved, using various one‐and two‐dimensional NMR experiments. Copyright © 2010 John Wiley & Sons, Ltd.     

Water Soluble Gold(I)‐diacetyl‐1,3,5‐triaza‐7‐phosphaadamantane‐arylazoimidazole Complexes: Synthesis and Spectroscopic Study

Reaction of [Au(DAPTA)(Cl)] with RaaiR’ in CH2Cl2 medium following ligand addition leads to [Au(DAPTA)(RaaiR’)](Cl) [DAPTA＝diacetyl-1,3,5-triaza-7-phosphaadamantane, RaaiR’＝p-R-C6H4-N＝N- C3H2-NN-1-R’, (1—3), abbreviated as N,N’-chelator, where N(imidazole) and N(azo) represent N and N’, respectively; R＝H (a), Me (b), Cl (c) and R’＝Me (1), CH2CH3 (2), CH2Ph (3)]. The 1H NMR spectral measurements in D2O suggest methylene, CH2, in RaaiEt gives a complex AB type multiplet while in RaaiCH2Ph it shows AB type quartets. 13C NMR spectrum in D2O suggest the molecular skeleton. The 1H-1H COSY spectrum in D2O as well as contour peaks in the 1H-13C HMQC spectrum in D2O assign the solution structure.     

Synthesis of N‐(Substituted aryl/cyclohexyl)‐N'‐[5‐bromo‐5‐nitro‐2‐oxido‐1,3,2‐dioxaphosphorinane‐2‐yl]ureas

N‐(Substituted aryl/cyclohexyl)‐N'‐[5‐bromo‐5‐nitro‐2‐oxido‐1,3,2‐dioxaphosphorinane‐2‐yl]ureas RR'P(O)NHC(O)NHR' (5) were synthesized by the reactions of 2‐bromo‐2‐nitro‐1,3‐propanediol (4) with chlorides of aryl/cyclohexyl carbamidophosphoric acids (3) in the presence of triethylamine at room temperature. Their ir, ¹H, ¹³C and ³¹P nmr spectral data are discussed.     

Covalent‐Bond Formation in the Course of the Inhibition of δ‐Chymotrypsin with trans‐Decalin‐Type Organophosphates: 31P‐NMR Evidence

Earlier investigations have shown that the irreversible inhibition of δ‐chymotrypsin with the axially substituted trans‐3‐(2,4‐dinitrophenoxy)‐2,4‐dioxa‐3λ⁵‐phosphabicyclo[4.4.0]decan‐3‐one (=2‐(2,4‐dinitrophenoxy)hexahydro‐4H‐1,3,2‐benzodioxaphosphorin 2‐oxide) proceeds under inversion of the configuration at the P‐atom. Since this assignment is based on the comparison of the respective chemical shifts with model compounds, the covalent nature of the binding interaction between enzyme and inhibitor was formulated in analogy. To prove this assumption, inhibition experiments were performed with the deuterated inhibitor (±)‐trans‐3‐(2,4‐dinitrophenoxy)‐2,4‐dioxa‐3λ⁵‐phospha(1,5,5‐²H₃)bicyclo[4.4.0]decan‐3‐one ((±)‐ 6a ). ³¹P{²H}‐NMR‐Spectroscopic monitoring of the reaction of stoichiometric amounts of the enzyme with (±)‐ 6a at pH 7.8 yielded the diastereoisomeric adducts 9 (−3.88 ppm) and 9′ (−3.96 ppm). Comparing the ³¹P chemical shifts of the corresponding deuterated covalent phosphoserine model compounds 8a/8a′ (−6.70 ppm, axial) and 8b/8b′ (−4.11/−4.13 ppm, equatorial) confirmed the inversion of the configuration at the P‐atom. ¹H‐Correlated ³¹P{²H}‐NMR spectra revealed a cross peak of the Ser¹⁹⁵‐H₂ (4.45 ppm) with the P‐atom of the inhibitor at −3.88/−3.96 ppm, thus establishing the covalent nature of the Ser¹⁹⁵−O−P bond.     

Diselenadiphosphetandiselenide und Triselenadiphospholandiselenide – Synthese und Charakterisierung mittels 31P‐ und 77Se‐Festkörper‐NMRSpektroskopie

Diselenadiphosphetane Diselenides and Triselenadiphospholane Diselenides – Synthesis and Characterization by ³¹P and ⁷⁷Se Solid‐State NMR Spectroscopy 1,3‐Diselena‐2,4‐diphosphetane‐2,4‐diselenides (RPSe₂)₂ with R = Me, Et, t‐Bu, Ph, 4‐Me₂NC₆H₄, 4‐MeOC₆H₄ have been synthesized by different methods. The insoluble compounds were investigated by ³¹P and ⁷⁷Se solid‐state NMR and the purity of the compounds has been checked by their CP MAS sideband NMR spectra. The structure of the investigated compounds has been confirmed by the isotropic and anisotropic values of the chemical shifts and the ¹J_P–Se coupling constants. In addition, two new 1,2,4‐triselena‐3,5‐diphospholane‐3,5‐diselenides, (RPSe₂)₂Se (R = Me, Et), formed under similar synthesis conditions, were investigated. Their structure was derived from the ⁷⁷Se satellites of ³¹P solution spectra and from solid‐state spectra. For (t‐BuPSe₂)₂ the experimentally obtained principal values of phosphorus and selenium shielding tensors are compared with values from IGLO calculations (HF und SOS DFPT). The calculated orientations of the principal axes are discussed.     

X‐ray crystal structure,NMR parameters,and conformational study of α‐aminopropanephosphonic acid

X‐ray structural data for α‐aminopropanephosphonic acid (APPA), together with ¹H NMR spectroscopy including PANIC and WIN‐DAISY spectral simulation, and theoretical calculations using the programs VAMP 4.4 (PM3) and GAUSSIAN 92 (3–21G**), confirm an antistaggered relationship between the methyl and phosphonic acid groups in this zwitterionic compound, both in the solid state and in aqueous solution. ³¹P{¹H} and ¹³C{¹H}‐NMR controlled titrations provide information on pK_a values, proton exchange, ion‐specific chemical shifts, and coupling constants in solution. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:314–325, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20609