Syn Rotamers Research Articles

Exploring the mechanisms of excited-state intramolecular proton transfer in hydroxyphenyl-benzimidazole derivatives: A theoretical perspective

We conducted a comprehensive theoretical exploration for the ESIPT mechanism in a set of HBI derivatives in THF solution (Cpd-A and Cpd-B, and three isomers: Cpd-1, Cpd-2 and Cpd-3), employing time-dependent density functional theory (TD-DFT) methods for the excited-state calculations. An energy scan for the excited-state proton transfer pathway indicates that both Cpd-A and Cpd-B exhibit a low transition barrier from Enol* to Keto*, with the energy of Keto* much lower than Enol* state, which implies a rapid ESIPT process. The high instability of Enol* state contradicts the experimental observed dual emission bands for Cpd-A, where the emission band predominantly contributed from Keto* state. We propose a new mechanism to account for this dual fluorescence phenomenon of Cpd-A, where the overall fluorescence band can be ascribed to the emissions from both Keto* and a stable rotamer of Cpd-A. Calculations suggest that Cpd-A can exist in both syn and anti rotamers, with a relatively low isomerization barrier of 14.0 kcal/mol. The coexistence of two stable isomers in solution gives rise to the phenomenon of dual emission for Cpd-A. Further investigation for the substituent effects on the ESIPT dynamics of three isomers (Cpd-1, Cpd-2 and Cpd-3) indicates that varying substituent positions can have a substantial impact on both ESIPT process and excited-state charge transfer. The methoxy group substitution proximate to the hydroxy functional group decreases the energy barrier for Enol*-Keto* transition, and also promotes a more substantial charge transfer. Our study demonstrates a new mechanism of the dual fluorescence observed for the target HBI derivatives, offering a novel understanding for the ESIPT mechanism in solvent.

Properties of 3-fluoroprop-2-enoic acids, chemical shifts and indirect spin-spin coupling constants: A DFT study

Nuclear magnetic resonance (NMR) parameters, shielding constants, and indirect spin-spin coupling constants (SSCC) in a large set of model compounds were calculated using the combination of the B3PW91, B3LYP, and BHandH functionals with the 6-311+(d,p), 6-311++G(d,p), 6-311++G(2d,p), and 6-311++G(3df, 3pd) basis sets, in order to verify the most appropriate methods for calculating these parameters. Selected methods were applied to calculate the NMR parameters in (2E)- and (2Z)-3-fluoroprop-2-enoic acids. Optimization of structures revealed four stable rotamers of each isomer, E and Z, of 3-fluoroprop-2-enoic acid. The internal molecular energy of s-cis and s-trans syn rotamers indicated that they are favorable in solution. All rotamers of 3-fluoroprop-2-enoic acid are coplanar except E s-trans anti, which has a "twisted" structure due to repulsion between hydrogen atoms CFH and HO. Topological analysis of the electronic structure of molecules including properties of critical points revealed noncovalent F...OH and F...HO bonds in Z s-trans syn and anti rotamers, respectively. The molecules of acid tend to form dimers and trimers in solution via hydrogen bonds O...H, CH...O, and CH...F, with binding energies ranging from a few to over a dozen kcal per mol. Theoretical chemical shifts and SSCCs were analyzed in detail to find a dependence on the geometry of individual rotameters. Calculations revealed a 5J(F,H) of -31 Hz in Z s-trans-anti rotamer containing the F...HO hydrogen bond, while this SSCC ranges from -1.9 to 1.4 Hz in the remaining rotamers. Intermolecular SSCCs across hydrogen bonds range from -3 to 7 Hz in dimers and trimers. Theoretical NMR parameters were compared with available experimental data.

Synthesis, spectral characterization and conformational assignment of N-formyl-2,7-diaryl-1,4-diazepan-5-ones as potent antibacterial agents and type I DHQase inhibitors

• Four N -formyldiazepan-5-ones are synthesized and characterized by IR, mass and NMR spectra. • The conformational assignment is made by NMR spectral studies. • All the formamides prefer to adopt flattened boat conformations. • Antibacterial efficacy for 9-12 have been evaluated by resazurin reduction assay. • Molecular docking is performed for 9-12 with type 1 3-DHQase protein target. Four new N -formyl-1,4-diazepan-5-ones 9-12 have been synthesized and their spectral characterization is made using IR, mass and NMR spectra. In NMR spectra, the compounds 9-12 show doubling of NMR spectral signals due to the delocalization of nitrogen lone pair into the carbonyl П cloud and thereby creating a partial double character at N C(= O ) bond which results in an equilibrium between syn and anti rotamers. The preferred conformations of N -formyl-1,4-diazepan-5-ones 9-12 are arrived from the NMR spectral data, dihedral angles (°) and destabilizing strain factors. The syn and anti rotamers of these compounds prefer to adopt equilibrium between flattened boat conformations with quasi-axial orientations of aryl groups at C-2 and C-7. Furthermore, all the compounds are active against all the tested bacterial strains. The compounds 9 & 10 against E. coli strain, compound 11 against B. cereus strain and compounds 11 & 12 against S. typhi strain show equal potency as that of standard drug Streptomycin. Hence, the formamides 9-12 are believed to be good antibacterial agents. The synthesised molecules are subjected to molecular docking studies with 3-dehydroquinate dehydratase (DHQase) protein. The molecular modelling studies exhibit high inhibition and binding energy are conforming to antibacterial activity. The compounds 9-12 exhibit better docking score and glide energy than that of DHQase co-crystallized ligand.

Losses of CO and CO2 upon collision-activated dissociation of substituted 2-methoxyphenoxides after methyl radical loss

Some deprotonated, substituted 2-methoxyphenols fragment by methyl radical loss followed by competing losses of CO and CO2 upon collisional activation in linear quadrupole ion trap mass spectrometers. These reactions were examined experimentally and computationally in order to determine their mechanisms. For deprotonated vanillin, the CO loss was found to involve ring contraction, with the highest free energy barrier of 58.0 kcal mol−1 (for the syn rotamer; here, syn refers to the relationship between the aldehyde oxygen atom and the oxygen atom of the methoxy group) for the entire process. The atoms lost in this fragmentation are the oxygen atom that was bound to the first eliminated methyl group and the aromatic carbon atom bound to this oxygen. Examination of carbon-13 labeled vanillin supports these assignments. Examination of several model compounds revealed that this reaction requires the presence of an electron-withdrawing substituent in the para-position relative to the phenol moiety. In contrast, the CO2 loss from deprotonated vanillin occurs via ring opening followed by re-cyclization and then ring contraction, leading to the loss of CO2 in a process wherein the highest free energy barrier is 84.5 kcal mol−1 (for the syn isomer). The atoms lost in this fragmentation are the carbon and oxygen atoms from the phenoxide group and the oxygen atom that was bound to the first eliminated methyl group, which is supported by examination of carbon-13 labeled vanillin. Despite the higher total free energy requirement, the CO2 loss is competitive with CO loss, possibly due to favorable entropy and low activation energy (free energy barrier of 48.9 kcal mol−1) for the first reaction step (the analogous value for CO loss is 58.0 kcal mol−1). The extent of CO2 loss is strongly affected by substituents – it either is not observed or is very slow for the other compounds studied here. For example, it is substantially less favorable than CO loss (highest free energy barrier 60.9 kcal mol−1) for deprotonated acetovanillone for which the first reaction step for CO2 loss has a substantially greater free energy barrier (60.6 kcal mol−1) than for vanillin.

Synthesis, spectral characterization, solution and solid-state conformations of N-nitroso-2,7-diaryl-1,4-diazepan-5-ones by NMR and XRD studies

Nitroso derivative of 2,7-diaryl-1,4-diazepan-5-ones 9–12 are synthesized and characterized using spectroscopic techniques such as IR, EI-MS and NMR spectra. The stereochemical investigation of nitroso compounds has been carried out with 1D (1H, 13C & DEPT-135) and 2D (COSY & HSQC) NMR spectral data. Rotational isomers (syn and anti rotamers) of 9–12 are identified and categorized by room temperature NMR spectral studies. Furthermore, the conformation of the ring and the orientation of NN=O function have been arrived on the basis of chemical shifts, coupling constants and dihedral angles. In solution state, syn and anti rotamers of the compounds 9–11 exist in equilibrium between flattened boat conformation with quasi-axial orientations of the aryl groups at C-2 and C-7. Nevertheless, compound 12 and its syn and anti rotamers prefer to adopt equilibrium between chair conformations with axial orientation of aryl substituents. In order to validate the solution state conformation, the compound 12 is crystallized and the crystal structure is solved by single crystal XRD study. The compound 12 exists in an alternate chair conformation and aryl groups at C-2 & C-7 occupy axial orientations in solid state also.

Vibrational Spectroscopy of a Potential Interstellar Ion: Protonated Methyl Formate

Abstract The abundance of methyl formate (MF, HCOOCH3) in star-forming regions of the interstellar medium (ISM) suggests the presence of protonated MF (H+MF). However, no spectroscopic data exist for isolated H+MF. Here, we address the vibrational properties of H+MF and its H+MF-L n≤2 clusters (L = Ar/N2) by infrared photodissociation (IRPD) spectroscopy and density functional theory calculations. Protonation of MF occurs at the CO oxygen, resulting in four different isomers arising from the syn/anti (s/a) and cis/trans (c/t) orientation between OCH3 and the excess proton. H+MF photofragments into protonated methanol by CO elimination. The IRPD spectrum exhibits redshifted OH stretch bands of the most stable H+MF(t/s) and H+MF(c/a) conformers because of the high internal energy required for dissociation. Tagging of H+MF with inert ligands drastically reduces both the internal energy and the dissociation threshold. The resulting higher-resolution IRPD spectra allow determination of the most stable H+MF rotamers as (t/s) and (c/a). In the cold H+MF-L dimers, the ligand forms an OH...L hydrogen bond, while bonding to the positively charged 2pz orbital of the carbonyl C atom is less favorable. The latter allows estimation of the free OH stretch fundamental of the most stable H+MF(t/s) rotamer as 3545 ± 5 cm−1. While for neutral MF the more stable syn rotamer MF(s) dominates the population in both the laboratory and the ISM (>99%), the anti conformer is substantially populated for H+MF (∼30%), which is rationalized by protonation-induced isomerization. This mechanism may lead to an enhanced abundance of MF(a) in certain regions of the ISM.

Far-Infrared Synchrotron Spectroscopy of a Potentially Important Interstellar Isotopologue of Vinyl Alcohol: CH2CHOD.

The far-infrared spectrum (100-500 cm-1) of a d1 isotopologue of the astrophysically important molecule, vinyl alcohol, is reported. We observed several low energy (OD) torsional bands: the fundamental and first two hot bands of the syn rotamer and the fundamental and first hot band of the (higher energy) anti rotamer. While the bands corresponding to the anti rotamer are somewhat obscured by rotational lines of water (making a full spectroscopic analysis unfeasible at this stage), the syn-vinyl alcohol bands are not, and a global fit was performed that included 4404 distinct infrared lines assigned in this work, in addition to 59 previously reported microwave lines. This simultaneous analysis of the torsional fundamental, torsional hot band, and pure rotational band of syn-vinyl alcohol allowed for determination of spectroscopic parameters in the first two torsionally excited states and for refinement of them in the ground state. These parameters should be useful in searches for both cold and warm CH2CHOD in interstellar molecular clouds.

Axial ligand mediated switchable rotary motions in a ferrocene-bridged diiron(III) porphyrin dimer

In the present work, we have utilized ferrocene-bridged diiron(III) porphyrin dimer and investigate the rotary motions mediated by axial ligands exploiting conformational flexibility of the ferrocene linker. Diiron(III) porphyrin dimer can switch easily between the syn and anti rotamers reversibly based on the axial coordination and thereby forming complexes with different structure and properties for the development of synthetic molecular machines. While the five-coordinate diiron(III) complex with chloride axial ligand and its μ-oxo dimer are in syn-conformation, their six-coordinate complexes are stabilized in anti-conformation. All the complexes are isolated in the solid state and five-coordinate complexes are also structurally characterized. Spectroscopic investigation through UV–visible spectra, solid-state Mössbauer, EPR, and 1H NMR studies confirm the presence of high and low-spin diiron(III) porphyrins, respectively, for five and six-coordinate complexes.

Theoretical insight to intermolecular hydrogen bond interactions between methyl N-(2-pyridyl) carbamate and acetic acid: substituent effects, cooperativity and energy decomposition analysis

In the present work, the hydrogen bond (HB) interactions between substituted syn and anti rotamers of methyl N-(2-pyridyl) carbamate and acetic acid were investigated using quantum mechanical (QM) calculations. The rotamers have two typical active sites to form hydrogen bonds with acetic acid, such that four stable complexes are found on the potential energy surface. The complexes in which the oxygen atom of carbamate acts as proton acceptor are stabilized by EWSs and are destabilized by EDSs. The trend in the effects of substituents is reversed in the other two complexes, in which the nitrogen atom of ring is involved in the interaction. According to energy data, the substituent effects on the interaction energy can be expressed by Hammett constants. The natural resonance theory (NRT) model was used to investigate the charge distribution on the carbamate group and to discuss the interaction energies. The individual HB energies were estimated to evaluate their cooperative contributions on the interaction energies of the complexes. In addition, the localized molecular orbital energy decomposition analyses (LMO-EDA) demonstrate that the electrostatic interactions are the most important stabilizing components of interactions.

Jet-Cooled Spectroscopy of ortho-Hydroxycyclohexadienyl Radicals.

The electronic spectra of the ortho-hydroxycyclohexadienyl radical have been observed following the supersonic expansion of the electric discharge products of phenol and water. Hydrogen atoms, split from water, add to the phenol ring at the ortho position, generating syn and anti rotamers with respect to the hydroxyl group. The D1 ← D0 transitions were recorded by resonance-enhanced multiphoton ionization spectroscopy. The spectrum of each isomer was isolated through hole-burning spectroscopy. The assignment and symmetry of the excited state are evaluated through ab initio calculations and are employed to assign each spectrum. Both rotamers are calculated to have a puckered ring in the excited state, leading to C1 symmetry. The spectrum of the anti isomer is assigned well using this symmetry; however, the syn isomer is assigned better in the C s symmetry of the ground state. We use Duschinsky matrices as a tool for the spectroscopist to determine which point group to use when ab initio calculations are ambiguous.

Stereochemical investigation of N-formyl-2,7-diphenyl-1,4-diazepan-5-ones by NMR spectroscopy and single crystal X-ray diffraction studies

A series of N-formyl-2,7-diphenyl-1,4-diazepan-5-ones 11–15 are synthesized in significant yields (86–92%) from their corresponding 2,7-diphenyl-1,4-diazepan-5-ones 6–10 using acetic-formic anhydride. Synthesized compounds 11–15 are characterised by their analytical and spectral (IR, Mass, 1D & 2D NMR) data. All the N–formyl compounds 11–15 show doubling of NMR signals due to the existence of syn and anti rotamers at RT which are unambiguously assigned by HETCOR spectra and ASIS method. The preferred conformation has been arrived by considering the chemical shifts, coupling constants, dihedral angles and destabilizing strain factors. The N-formyl-2,7-diphenyl-1,4-diazepan-5-ones 11–15 are best accommodated in a coplanar orientation of formyl function and flattened boat conformation of the ring where the phenyl groups are occupying pseudo-axial orientations in solution state. Further, dynamic NMR study is carried out for 14 from 28 °C to 116 °C and the calculated average energy barrier is 84.4 kJ mol−1. The single crystal X-ray diffraction study on N-formyl-2,7-diphenyl-1,4-diazepan-5-one 13 shows that the molecule adopts distorted boat conformation with coplanar orientation of formyl group.

Conformational dynamics of 4-formylaminoantipyrine based on NMR and theoretical calculations

We investigated the metamizole metabolite 4-formylaminoantipyrine (4-FAA) by 1H dynamic nuclear magnetic resonance. 4-FAA exhibits a carbon-nitrogen partial double bond that rotates slowly enough, on a resonance time scale, to provide the simultaneous spectra of two rotamers. We examined various solvents in an attempt to understand how protic and aprotic environments influence the anti and syn rotamer equilibriums. Moreover, we compared experimental data and theoretical calculations to evaluate the thermodynamic parameters of the rotational process.

Conformational behavior, redox and spectroscopic properties of gold dithiolene complexes: [Au(iPr-thiazYdt)2]−1 (Y = O, S, Se)

Three monanionic gold dithiolene complexes with different exocyclic chalcogen atoms (O, S, Se) on the N-isopropyl-1,3-thiazoline-2-chalcogenone-4,5-dithiolate ligand, have been synthetized with the aim of modulating their properties. Due to the presence of the isopropyl (iPr) group in the plane of the thiazoline-2-chalcogenone ring, different syn and anti rotamers can exist, in solution and in the solid state. Characterization of these complexes by spectroscopic and electrochemical methods was carried out in order to investigate the influence of the size, electronegativity and polarizability of the exocyclic chalcogen atom. The molecular structure of the three anionic complexes [Au(iPr-thiazYdt)2]−1, with Y=O, S, Se, were established by single crystal X-ray diffraction studies. Theoretical calculations carried out at the DFT levels were realized on the three possible rotamers, syn/syn, syn/anti and anti/anti of the trans-[Au(iPr-thiazYdt)2]−1 complexes.

Synthesis and Structure of a Functionalized [9]Cycloparaphenylene Bearing Three Indeno[2,1-a]fluorene-11,12-dione-2,9-diyl Units.

A synthetic pathway to a functionalized [9]cycloparaphenylene bearing three indeno[2,1-a]fluorene-11,12-dione-2,9-diyl units in the macrocyclic ring structure ([3]CIFO) has been developed. The 1H and 13C NMR spectra show that only the anti rotamer (anti-[3]CIFO) is produced. DFT calculations indicate that the anti rotamer is thermodynamically more stable than the syn rotamer by 4.3 kcal/mol, and the rotational barrier from the anti to syn rotamer is estimated to be 23.3 kcal/mol. The UV-vis and fluorescence spectra and cyclic voltammogram of anti-[3]CIFO were investigated.

A Very Rare Example of a Structurally Characterized 3'-GMP Metal Complex. NMR and Synthetic Assessment of Adducts Formed by Guanine Derivatives with [Pt(Ltri)Cl]Cl Complexes with an N,N',N″ Tridentate Ligand (Ltri) Terminated by Imidazole Rings.

[Pt(N(R)-1,1'-Me2dma)Cl]Cl complexes with tridentate ligands (bis(1-methyl-2-methylimidazolyl)amine, R = H; N-(methyl)bis(1-methyl-2-methylimidazolyl)amine, R = Me) were prepared in order to investigate Pt(N(R)-1,1'-Me2dma)G adducts (G = monodentate N9-substituted guanine or hypoxanthine derivative). Solution NMR spectroscopy is the primary tool for studying metal complexes of nucleosides and nucleotides because such adducts rarely crystallize. However, [Pt(N(H)-1,1'-Me2dma)(3'-GMPH)]NO3·5H2O (5) was crystallized, allowing, to our knowledge, the first crystallographic molecular structure determination for a 3'-GMP platinum complex. The structure is one of only a very few structures of a 3'-GMP complex with any metal. Complex 5 has the syn rotamer conformation, with 3'-GMP bound by N7. All Pt(N(R)-1,1'-Me2dma)G adducts exhibit two new downfield-shifted G H8 signals, consistent with G bound to platinum by N7 and a syn/anti rotamer mixture. Anticancer-active monofunctional platinum(II) complexes have bulky carrier ligands that cause DNA adducts to be distorted. Hence, understanding carrier-ligand steric effects is key in designing new platinum drugs. Ligand bulk can be correlated with the degree of impeded rotation of the G nucleobase about the Pt-N7 bond, as assessed by the observation of rotamers. The signals of syn and anti rotamers are connected by EXSY cross-peaks in 2D ROESY spectra of Pt(N(H)-1,1'-Me2dma)G adducts but not in spectra of Pt(N(H)dpa)G adducts (N(H)dpa = bis(2-picolyl)amine), indicating that rotamer interchange is more facile and carrier-ligand bulk is lower in Pt(N(H)-1,1'-Me2dma)G than in Pt(N(H)dpa)G adducts. The lower steric hindrance is a direct consequence of the greater distance of the G nucleobase from the H4/4' protons in the N(R)-1,1'-Me2dma carrier ligand in comparison to that from the H6/6' protons in the N(H)dpa carrier ligand. Although in 5 the nucleotide is 3'-GMP (not the usual 5'-GMP) and the N(H)-1,1'-Me2dma carrier ligand is very different from those typically present in structurally characterized Pt(II) G complexes, the rocking and canting angles in 5 adhere to long-recognized trends.

The near ultraviolet photodissociation dynamics of 2- and 3-substituted thiophenols: Geometric vs. electronic structure effects.

The near ultraviolet spectroscopy and photodissociation dynamics of two families of asymmetrically substituted thiophenols (2- and 3-YPhSH, with Y = F and Me) have been investigated experimentally (by H (Rydberg) atom photofragment translational spectroscopy) and by ab initio electronic structure calculations. Photoexcitation in all cases populates the 11ππ* and/or 11πσ* excited states and results in S-H bond fission. Analyses of the experimentally obtained total kinetic energy release (TKER) spectra yield the respective parent S-H bond strengths, estimates of ΔE(A∼-X∼), the energy splitting between the ground (X∼) and first excited (A∼) states of the resulting 2-(3-)YPhS radicals, and reveal a clear propensity for excitation of the C-S in-plane bending vibration in the radical products. The companion theory highlights roles for both geometric (e.g., steric effects and intramolecular H-bonding) and electronic (i.e., π (resonance) and σ (inductive)) effects in determining the respective parent minimum energy geometries, and the observed substituent and position-dependent trends in S-H bond strength and ΔE(A∼-X∼). 2-FPhSH shows some clear spectroscopic and photophysical differences. Intramolecular H-bonding ensures that most 2-FPhSH molecules exist as the syn rotamer, for which the electronic structure calculations return a substantial barrier to tunnelling from the photoexcited 11ππ* state to the 11πσ* continuum. The 11ππ* ← S0 excitation spectrum of syn-2-FPhSH thus exhibits resolved vibronic structure, enabling photolysis studies with a greater parent state selectivity. Structure apparent in the TKER spectrum of the H + 2-FPhS products formed when exciting at the 11ππ* ← S0 origin is interpreted by assuming unintended photoexcitation of an overlapping resonance associated with syn-2-FPhSH(v33 = 1) molecules. The present data offer tantalising hints that such out-of-plane motion influences non-adiabatic coupling in the vicinity of a conical intersection (between the 11πσ* and ground state potentials at extended S-H bond lengths) and thus the electronic branching in the eventual radical products.

Photochemical Reaction of OCSe with ClF in Argon Matrix: A Light-Driven Formation of XC(O)SeY (X, Y = F or Cl) Species.

The photochemistry of OCSe with ClF trapped together in argon matrices at cryogenic temperatures has been explored and the first interhalogen representatives of the elusive XC(O)SeY family, namely syn-ClC(O)SeF, anti-ClC(O)SeF, syn-FC(O)SeCl, and anti-FC(O)SeCl, as well as the hitherto triatomic species ClSeF complexed by a CO molecule, were obtained. Both ClC(O)SeF conformers appear to be produced independently by photolysis of the respective precursors; while formation of both FC(O)SeCl structures is ruled by the presence of an angular molecular complex OCSe···Cl-F formed prior to photolysis. This latter photochemical pathway seems to favor the formation of the less stable anti-FC(O)SeCl structure instead of the more stable syn- one. With the aid of quantum chemical calculations, using ab initio, DFT, TDDFT, and CASSCF methods, the mechanism for this photochemical reaction is rationalized both in terms of radical processes as well as a photoinduced electron transfer occurring into the OCSe···Cl-F complex. Also a singlet-triplet conical intersection between anti and syn rotamers of the FC(O)SeCl molecule is theoretically explored.

Guanine nucleobase adducts formed by a monofunctional complex: [Pt(N-(6-methyl-2-picolyl)-N-(2-picolyl)amine)Cl]Cl

Monofunctional Pt(II) complexes bind to G residues in DNA and, if the carrier ligands are bulky, cause DNA structural distortions that lead to anticancer activity. We assessed the steric effects of the tridentate carrier ligand, N(H)6-Medpa (N-(6-methyl-2-picolyl)-N-(2-picolyl)amine), bearing a 6-methyl group and a 6′-proton projecting toward the nucleobase in Pt(N(H)6-Medpa)G adducts (G=9-ethylguanine, 3′-GMP, 5′-GMP, 5′-GTP). Pt(N(H)6-Medpa)G adducts form syn and anti rotamers with the guanine O6 and the central N–H of N(H)6-Medpa on the same or opposite side of the coordination plane, respectively. Pt(N(H)6-Medpa)G adducts have some properties (ease of rotamer interchange and extent of conversion to bis adducts, Pt(N(H)6-Medpa)G2) intermediate to properties reported for analogs having a tridentate ligand with zero or two methyl groups. However, in comparison, the syn rotamer of Pt(N(H)6-Medpa)G adducts has an unexpectedly high abundance. This result is attributable to guanine base canting, such that the 6-membered guanine ring is positioned away from the bulky 6-Me group. This canting both relieves electrostatic repulsion between the partially positive H6′ and the guanine H8 protons and creates a favorable electrostatic attraction between the H6′ proton and the partially negative guanine O6. This combined information provides insight useful for designing monofunctional anticancer agents.

Synthesis, characterisation, stereochemistry and dynamic NMR studies of N-nitroso and N-formyl-t-3-isopropyl-r-2,c-6-bis(4-methoxyphenyl)piperidin-4-ones

The synthesis, characterisation and stereochemical investigations were made for N-nitroso (2) and N-formyl (3) derivatives of t-3-isopropyl-r-2,c-6-bis(4-methoxyphenyl)piperidin-4-one (1) using IR, mass, 1D and 2D NMR spectral studies. The compound 1 prefers to adopt a chair conformation with equatorial orientations of all substituents. The compounds 2 and 3 showed doubling of all the NMR spectral signals corresponding to syn and anti rotamers at RT and 223K, respectively. The syn and anti rotamers of 2 exist in an equilibrium between alternate chair (CA) and twist boat (TB1) conformations, respectively. The syn and anti rotamers of 3 exist in TB1 conformation. The stereodynamics of compounds 2 and 3 have been investigated using dynamic 1H NMR spectra and the calculated average energy barriers for N-NO and N-CHO rotations are found to be 77.76kJmol−1 and 68.18kJmol−1, respectively.

Synthesis, characterisation, stereochemistry and biological activity of N-formylpiperidin-4-ones

A new series of N-formyl-2,6-bis(4-methoxyphenyl)piperidin-4-ones 5–8 has been synthesized and characterised using IR, mass and 1H, 13C, DEPT and 2D (COSY and HSQC) NMR spectral techniques. The NMR spectral data indicated that the N-formylpiperidin-4-ones 5–8 prefer to exist in a conformational equilibrium between a syn rotamer with a twist boat conformation (TB1) and an anti rotamer with a twist boat conformation (TB2) in solution. The stereodynamics of these systems have been studied by recording the dynamic 1H NMR spectra of compound 5, and the energy barrier for the N-CO rotation was determined to be 64.3kJ/mol. All of the synthesized compounds (5–8) were screened for their biological activity.