Search

The new terthiophene sulfonamide derivative, TTS, was synthesized and its IR, VCD, UV and ECD spectra were measured and interpreted by means of the DFT calculations. The TTS conformational space analyzed at the molecular mechanics, B3LYP/TZVP/PCM, and B3LYP/def2TZVP/PCM levels, was reduced to 72 conformers none of which appeared to be definitely dominant. A detailed examination of the slight deviations in mutual positions of the three thiophene rings revealed that for each conformer an additional 16 minima are apparently important but only six of them appear to be meaningful in 300 K. Apart from the permanent stereogenic center at the C6 carbon atom, the N-atom constitutes another (labile) stereogenic center connected to the presence of a lone electron pair at this very atom. This is significant because we found that the most stable conformers exhibit almost exclusively the (S)-configuration at the N-atom. The experimental IR and VCD spectra of TTS were fairly well reproduced if its monomers and dimers were taken into account. On the other hand, the experimental ECD spectra were difficult to reproduce because the spectra with slightly deviated thiophene rings produce practically mirror image ECD spectra. Calculated and recorded VCD spectra confirm configuration at the C6 of TTS, which was earlier predicted using stereochemical model for 1,2-addition to N-sulfinylimines proposed by Ellman.

Undecathiophenes substituted by chiral and achiral groups were studied using DFT method. The substituent shift from one end to the other was monitored for: relative energy, the SRCM chirality measure, the chiral Wiener index, the HOMO-LUMO gap, HOMA and NICS aromaticity indices, and theoretical VCD spectrum. For both, all-trans and one-cis conformations, structures substituted at the end were ca. 10 kJ/mol more stable than the other isomers. The SRCMs fluctuations with the conformation made this parameter not useful, but, the topological chiral Wiener index displayed regular yet non-linear changes with the substituent position enabling differentiation of the chiral systems. The HOMO-LUMO gap increased with the substituent shift towards the central ring. It varies regularly with the Wiener index for all-trans but irregularly for one-cis conformers, indicating strong response of the gap on slight conformational changes. The aromaticity indices adopted to linear systems indicated the all-trans to be a bit less delocalized than the one-cis isomers. Finally, the calculated VCD spectra were indicated possibility to monitor the position of the chiral substituent along the all-trans and one-cis structures.

The primary purpose of this work was to demonstrate the suitability of circular dichroism (CD) spectroscopy in stereochemical studies of α,β-unsaturated oximes, with particular emphasis on determination of E and Z geometry of the oxime double bond. As models for this study, O-phenyl and O-triphenylmethyl (trityl) oximes of 4-hydroxy-2-methylcyclopent-2-en-1-one were selected. These model compounds differ in both absolute configuration at C4 carbon atom and E-Z configuration of the oxime double bond. The basic dichroic technique applied was electronic circular dichroism (ECD) assisted by quantum-chemical calculations and vibrational circular dichroism (VCD) for selected cases. Such an approach enabled effective implementation of both goals. Thus, we were able to associate the signs of Cotton effects in the range of 190-240 nm with the absolute configuration at C4 and within 240-300 nm with the E- or Z-geometry of the oxime double bond. Within this work, optical activity of the protecting trityl group was also studied towards formation of the propeller-shaped conformations by using the same combined CD/DFT methodology. As shown, the helical structure of the trityl group has a considerable influence on the ECD spectra. However, the MPM and PMP conformers of the trityl group are in fact almost equally populated in the conformational equilibrium, making it impossible to distinguish them. On the other hand, rotamers of the hydroxyl group at C4 show a decisive impact on the VCD spectra in both phenoxy and trityl oximes.

We studied the conformation and hydration of the SO 3 -Ph-BTP ligand used as hydrophilic actinide and lanthanide separating agent using DFT methods. To avoid a large conformational space, changes in conformation and hydration were considered step-by-step. The central BTP system of the SO 3 -Ph-BTP ligand can be slightly non-planar in the gas phase, but in an aqueous solution it adopts the planar BTP- cc -aq conformation, known from metal complexes with BTP-like ligands. Out of a dozen conformations of protonated BTP, the most stable appeared to be the one protonated at the pyridine N-atom. The analysis of the conformation and hydration of the larger Ph-BTP system indicates that in water the proton dissociates from the protonated BTP core to form a hydronium ion, which additionally interacts with two water molecules H-bonded to triazine's N2-atoms. Considering 24 different protonated Ph-BTP conformers surrounded by five water molecules led us to the conclusion that the core of the most stable form is practically identical to the most stable hydrated and protonated BTP form. Modelling the hydration of both every part of the SO 3 -Ph-BTP ligand independently and the whole SO 3 -Ph-BTP ligand indicated that the hydronium ion formed near the SO 3 H groups can migrate and be stabilized near the center of the SO 3 -Ph-BTP ligand. Thus, in the process of actinide and lanthanide extraction from acidic solutions, the metal ions compete with the hydronium ion for the position at the ligand center.

The steroidal alkaloid solasodine (1) undergoes inversion of configuration at the C-22 spiro atom when treated with acetic anhydride-pyridine at ambient temperature. The basic solvolysis of the N, O-diacetyl derivative (2) reverses the reaction, yielding the starting solasodine (1). The mechanisms of both processes (acetylation and deacetylation) were studied in terms of possible reaction pathways.

The primary goal of this work is to clarify why 2-(hydroxymethyl)-2,5,7,8-tetramethyl-chroman-6-ol {(S)-TMChM} deviates from the chromane helicity rule under solvent change. The rule, applicable to determining the absolute configuration of molecules containing the chromane chromophore, binds the sign of the 1Lb Cotton effect (CE) with the helicity of the dihydropyran ring. In case of TMChM, however, this CE exhibits extreme solvent dependence: it is negative in non-coordinating solvents and positive in coordinating ones, irrespective of the helicity of the heterocyclic ring. TD-DFT calculations using PCM and hybrid solvation models were performed to explain origin of this phenomenon. It turned out that the 1Lb CE sign directly depends on the position of the phenolic OH group at carbon atom C6 (OHC6). In the absence of interactions with solvents (as in CCl4 or nC6H14) or when a solvent plays proton donor role (as in CHCl3), the OHC6 lies in the phenyl plane and the 1Lb CE sign follows the P/M helicity rule. In contrast, in proton acceptor solvents, like DMSO, CH3OH or CH3CN, the OHC6 group is deflected from the phenyl plane, and the 1Lb CE sign of individual (S)-TMChM conformers depends on the sector in which the OHC6 is located. Thus, in solution, the 1Lb CE sign is an average over different orientations of the OHC6 group and can be positive (as in DMSO and CH3OH) or negative (as in CH3CN) which means that it does not follow the chromane helicity rule. The impact of OHC6 on the 1Lb CE sign and thus the conclusions for the stereochemistry of chromans are demonstrated here for the first time. Additionally, a comparison of experimental and simulated ECD spectra, supported by VCD data, allowed to determine the geometry of intermolecular clusters formed in different solvents.

The IR and vibrational circular dichroism (VCD) spectra of both enantiomers of Me-, iPr-, nBu-, Ph-, and CH2 Ph-substituted isoindolinones in solution and KBr pellets were measured and interpreted by DFT calculations. The spectra in solution revealed no important differences in the C=O stretching vibration region while the interpretation of very distinct spectra taken in pellets required determining the crystal structures. The studied compounds crystallized in the P21 21 21 (Me, iPr, CH2 Ph), P31 (nBu), and P21 (Ph) space groups. We found that the quality of simulated spectra strongly depends on the substituent, the structure of the molecular cluster assumed, basis set, and use of the dispersion correction. The IR spectra can be reproduced well based on the simplest linear arrangement of hydrogen-bonded chains mimicking the molecular arrangement in the crystals. We found no common approach to reproduce all the registered VCD spectra in the crystal phase. For the Me and nBu isoindolinones, the VCD pattern was the best reproduced by full optimization of the selected large molecular clusters. For iPr, Ph and CH2 Ph derivatives optimizing only the position of H-atoms in a fragment frozen as in the crystal provides the best results. Such an approach can reduce the computation time from months to one week.

Two enantiomers of 2-methyl-N-(1-thien-2-ylethyl)propane-2-sulfonamide (TSA) were synthesized, and their VCD, ROA, IR, and Raman spectra were registered. The solved (S)-TSA X-ray structure shows a disorder connected to the presence of two TSA conformers differing by a slight rotation of the thiophene ring. Two molecules in the unit cell of the monoclinic P21 crystal form a net of NH···OS and C*H···OS hydrogen bonds. Out of a series of computational levels tested to interpret the spectra, the B3LYP functional combined with the def2TZVP basis set satisfactorily reproduces the experimental VCD and ROA spectra. To simulate the VCD spectra of TSA enantiomers in KBr pellets, dimers and tetramers, with two different positions of the thiophene ring, were considered. The VCD spectra measured in CDCl3 are completely different from those taken in KBr due to the conformational freedom of TSA in chloroform. Seven TSA conformers fall into two groups of opposite configurations at the pyramidal N atom forming the additio...

The aim of the present work was to verify the usefulness of dimolybdenum tetrakis(μ-pivalate) and tetrakis(μ-isovalerate) as auxiliary chromophores for determining the absolute configuration of optically active vic-diamines, vic-amino alcohols, α-amino and α-hydroxy acids by means of electronic circular dichroism (ECD). To this end, a series of measurements designed to check the dependence of ECD and UV-Vis spectra on time and concentration was carried out. The experimental results were supported by a separate set of detailed DFT calculations. The results obtained allowed us to determine the most probable structure of dominating chiral complexes formed in situ in solution for all ligands studied.

In this paper we provide a computational study of the l-methionine conformational landscape and VCD spectra in the gas phase and a water environment simulated by implicit PCM and the hybrid model, i.e., a combination of explicit "microsolvation" and implicit models. In the gas phase, two groups of conformers differing in H-bonding, i.e., OH···NH2 and NH···O═C, could be distinguished based solely on the IR ν(OH) and ν(NH) stretching vibrations range. On the other hand, VCD better reflected chain differences. The most stable OH···NH2 conformer was predicted to be easily detected, and the presence of two out of four NH···O═C conformers could be confirmed. Three zwitterionic methionine conformers were shown to dominate in water. Their VCD spectra, simulated within the hybrid model at the B3LYP-IEF-PCM/aug-cc-pVDZ level of theory, indicated that they could be recognized in the mixture. Use of the hybrid model is crucial for good reproduction of the hydrogen bonding pattern in the VCD spectra of methionine in water solution. However, the 1300-800 cm(-1) region of the skeleton vibrations of methionine appeared to be relatively insensitive to the model of the solvent.

Chiral quaternary ammonium salts, catalysts for chiral Darzens reaction of α-chloroacetic acid esters with benzaldehyde to yield glycidates in phase-transfer catalysis conditions, were studied by using the DFT/B3LYP/6-31G∗∗ calculations. Structure and energetics of several complexes between the chiral Darzens reaction catalysts and α-haloacetic ester carboanion were examined. Based on comparison of the complex stabilization energies and experimental ee values it was shown that the complex interaction energy alone is not a crucial parameter for catalyst to be efficient in asymmetric synthesis. A catalyst design was also tried, however, despite the interaction energy for the designed catalyst increased the geometrical arrangement of the reactant and the catalyst favoured a racemic rather than an asymmetric reaction.

The Darzens reaction leading to α,β-epoxy esters was modelled at the B3LYP/aug-cc-pVDZ level. Experimentally, the reaction proceeds at boundary between two phases, water and a non-polar, therefore, the two environments were considered in the simulations. The calculations show the Darzens reaction to be a stepwise process both in the gas phase and in solvents (toluene, acetonitrile, and water). In all considered environments, the first barrier, TS1, associated with formation of an intermediate, is much higher than TS2 associated with the closing of the epoxy ring with the simultaneous Cl− ion release. Therefore, the first process is the rate limiting step of the reaction. TS1 is the lowest for the gas phase, next in toluene, whereas the highest in acetonitrile and water. The same holds true for the small TS2 barrier which is especially low in toluene (0.45 kcal/mol = 157 cm−1). However, the barrier is genuine, because the collective Cl–C4 elongating along with epoxy closing/opening mode in the intermediate and in the product have energies definitely below the barrier.

Based on the B3LYP and MP2/aug-cc-pVDZ calculations, 51 cysteine conformers were found to be stable in the gas phase. The calculations were repeated for the most stable eight structures by using the aug-cc-pVTZ basis set. To estimate the influence of water on the cysteine conformation, the IEF-PCM/B3LYP/aug-cc-pVDZ calculations were carried out and showed 44 neutral and 12 zwitterion conformers to be stable in the water solution. The most stable cysteine structure in water appeared to be the zwitterionic conformer quite similar to the molecule observed in the crystal state.

A new oxidizing system for olefins, consisting of benzeneseleninic anhydride and trimethylsilyl triflate, was studied. The highly reactive benzeneseleninyl cation is presumably formed under these conditions. It has been shown that different products are formed with this species depending on the specific structure of olefin. The 1,1-disubstituted olefins afforded mostly α,β-unsaturated carbonyl compounds. The sterically encumbered tri- or tetrasubstituted olefins yielded 1,2- or 1,4-dihydroxylated products, presumably via four-membered cyclic intermediates.

A new oxidizing system for olefins, consisting of benzeneseleninic anhydride and trimethylsilyl triflate, was studied. The highly reactive benzeneseleninyl cation is presumably formed under these conditions. It has been shown that different products are formed with this species depending on the specific structure of olefin. The 1,1-disubstituted olefins afforded mostly α,β-unsaturated carbonyl compounds. The sterically encumbered tri- or tetrasubstituted olefins yielded 1,2- or 1,4-dihydroxylated products, presumably via four-membered cyclic intermediates.

The DFT calculations using B3PW91 hybrid functional and 6-311++G** basis set were performed for the two most stable isomers of cytisine ( 1a and 1b ). The conformation 1a differs from 1b by the orientation ( equatorial and axial , respectively) of the hydrogen atom at the piperidine nitrogen atom. In terms of the Gibbs free energy, the conformation 1a is less stable than 1b by 0.25 kcal mol −1 , only. The isomers are separated by 3.6 kcal mol −1 —an activation energy barrier, which is higher in energy than the vibrational modes inverting one isomer into another. Presence of such a barrier explains the existence of the two isomers ( equatorial and axial ) observed previously in apolar solvents.

Infrared and Raman spectra were recorded for solid cytisine—an agonist of nicotinic acetylcholine receptors (nAChRs), and analysed with help of the semiempirical (AM1) and ab initio {DFT(B3PW91)/6-311++G∗∗} calculations performed for monomeric and associated structures (dimer, trimer and tetramer). Among two stable conformers of cytisine (1a and 1b) identified in solution, only one (1a) is present in the solid state, where it is stabilized by intermolecular H-bonds (  C  O ⋯ HN  ). Two different environments for the associated molecules give two different spectral properties. Two component bands can be distinguished for the piperidine ν(NH) and γ(NH) as well as for the pyridine ν(CH), ν(CO) and ν(CC) contours.

Model chiral β -lactam molecules, (3 S )-and (4 R )-fluoro-2-azetidinone, were calculated at the B3PW91/aug-cc-pVTZ level, to be hydrogen bonded with the achiral HX molecule (X=F, Cl, Br). Two stable structures of the complex are possible: a cyclic or a bent H-bond, in which the HX molecule interacts with the CO group and is either close to NH or CH 2 (CHF) moiety, respectively. The VCD effect of these two forms differs in several respects, however, the main difference is the sign of the VCD rotational strength of the ν (HX) stretching vibrations revealing the geometry of the hydrogen bond complex.

The theoretical geometries, rotational constants, VCD, and IR spectra for the chiral ( S )-HXCCCFH (X=F, Cl, Br) allene molecules were calculated at the B3PW91/aug-cc-pVTZ level. We have shown that there is plausible adequacy between IR spectrum of ( S )-1,3-difluoroallene molecule calculated at B3PW91/aug-cc-pVTZ level and experimental spectra of the racemate system. For the other molecules studied, the experimental spectra were not published, yet, although, some results reported earlier for alkilohalogenoallenes are in line with our findings. The halogen influence on the VCD and IR spectra of the studied molecules is discussed.

Halogenoazetidinones are important as synthetic intermediates for preparation of halogen β-lactam (2-azetidinone) antibiotics and as building blocks for carbohydrates and amino acids. In this paper, we consider the influence of the halogen atom, substituted at the C4 position of the 2-azetidinone ring, on the geometry, IR, Raman, and vibrational circular dichroism spectra. The vibrational spectra were calculated for the chiral 4-(R)-X-2-azetidinone (X=F, Cl or Br) molecules at the B3PW91/aug-cc-pVTZ level. It was shown that the geometry of the molecules studied do not change much upon the change of the halogen atom. In case of the vibrational spectra, the position but even more the intensities depend strongly on the kind of halogen substituent.

DFT (B3PW91/6-31G** and B3PW91/6-311G**) calculations were performed for dibenzylcarbamic acid, either monomer or dimer (DBCAD). Six possible structures of the dimer were considered. Calculated geometrical parameters of the most stable dimer were compared with those published for the dibenzylcarbamic acid dimer crystalline solid. The calculated IR spectrum was used for the assignment of the frequencies observed in the experimental IR spectrum of dimer dibenzylcarbamic acid.

The oxetane⋯HCl and thietane⋯HCl complexes have recently been studied by rotational spectroscopy in a supersonic jet. In this Letter we report on stability, axial, and equatorial HCl arrangement in the complexes studied by means of MP2 calculations. The shape of the potential functions was studied for the ring-puckering and HCl inversion motions. For the oxetane complex, the barrier of the ring-puckering is small enough to be overcome by the ring-puckering vibration. For the thietane complex, the analogous barrier is higher than the vibration energy. Therefore, one oxetane and two thietane complex conformations were observed in the experiment.

The theoretical thermodynamic stability was calculated for products of cycloaddition of vinylimine to ketene and isocyanic acid to allene by using the MP2, DFT(B3PW91), and HF methods involving the 6-311++G** basis set. These cycloaddition reactions could yield fourteen different molecules; practically however, free Gibbs energies calculated for the considered molecules suggest that only 4- and 3-methylene-β-lactams can be formed in observable amounts. For these particular isomers the heats of formation, geometry, rotational constants, harmonic vibrational frequencies, infrared intensities, Raman activities, depolarisation ratios, and 1H, 13C, 17O and 15N NMR spectra were evaluated and discussed. The PED analysis carried out for theoretical IR spectra allowed us to assign vibrations of the two isomers. The IR and NMR assignments form a basis for the elucidation of future experimental data.

Theoretical Gibbs free energies have been determined for a set of cycloaddition products of allene with CO 2 , CS 2 or OCS molecules, and of CH 2 C X with CH 2 C Y molecule (X, Y=O, S). Each of the cycloaddition reactions leads to one or two isomeric products with four-membered heterocyclic ring. Theoretical thermochemical data suggest that the isomers in which sulphur atom is build into the four-membered ring can be easily formed in different reactions whereas formation of those with oxygen atom in the ring strongly depends on the considered reaction. Analysis of the theoretical 1 H and 13 C chemical shifts forms a basis for the detection of the isomer traces in reaction mixtures as well as for the elucidation of future experimental spectra.

Theoretical infrared spectra of diketene (4-methylene-2-oxetanone), its 3- and 2-methylene isomers and their mono- and disulphur analogues were calculated at the MP2/6-311++G∗∗ level. The effect of methylene and sulphur substitution on the IR spectra is discussed in terms of potential energy distribution (PED) analysis.

Vibrational circular dichroism (VCD) chirality transfer occurs when an achiral molecule interacts with a chiral one and becomes VCD-active. Unlike for H-bonds, for organic electron donor-acceptor (EDA) complexes this phenomenon remains almost unknown. Here, the VCD chirality transfer from chiral quinine to achiral BF3 is studied at the B3LYP/aug-cc-pVDZ level. Accessibility of four quinine electron donor sites changes with conformation. Therefore, the quinine conformational landscape was explored and a considerable agreement between X-ray and the most stable conformer geometries was achieved. The BF3 complex through the aliphatic quinuclidine N atom is definitely dominating and is predicted to be easily recognizable in the VCD spectrum. Out of several VCD chirality transfer modes, the ν(s)(BF3) mode, the most intense in the entire VCD spectrum, satisfies the VCD mode robustness criterion and can be used for monitoring the chirality transfer phenomenon in quinine···BF3 system.

Stabilization energies of the electron donor–acceptor sulfinimine···BF3 complexes calculated at either the B3LYP/aug-cc-pVTZ or the MP2/aug-cc-pVTZ level do not allow to judge, whether the N- or O-atom in sulfinimine is stronger electron-donor to BF3. The problem seems to be solvable because chirality transfer phenomenon between chiral sulfinimine and achiral BF3 is expected to be vibrational circular dichroism (VCD) active. Moreover, the bands associated with the achiral BF3 molecule are predicted to be the most intense in the entire spectrum. However, the VCD band robustness analyses show that most of the chirality transfer modes of BF3 are unreliable. Conversely, variation of VCD intensity with change of intermolecular distance, angle, and selected dihedrals between the complex partners shows that to establish the robustness of chirality transfer mode. It is also necessary to determine the influence of the potential energy surface (PES) shape on the VCD intensity. At the moment, there is still no universal criterion for the chirality transfer mode robustness and the conclusions formulated based on one system cannot be directly transferred even to a quite similar one. However, it is certain that more attention should be focused on relation of PES shape and the VCD mode robustness problem. Chirality. © 2011 Wiley Periodicals, Inc.

The reaction paths of [2 + 2] cycloadditions of allene (H2C=C=CH2) to isocyanic acid (HN=C=O) and ketene (H2C=C=O) to vinylimine (H2C=C=NH), leading to all the possible 14 four-membered ring molecules, were investigated by the MP2/aug-cc-pVDZ method. In the two considered reactions, the 2-azetidinone (beta-lactam) ring compounds were predicted to be the most stable thermodynamically in the absence of an environment. Although 4-methylene-2-azetidinone is the most stable product of the ketene-vinylimine cycloaddition, its activation barrier is higher than that for 4-methylene-2-iminooxetane by ca. 6 kcal/mol. Therefore, the latter product can be obtained owing to kinetic control. The activation barriers in the allene-isocyanic acid reactions are quite high, 50-70 kcal/mol, whereas in the course of the ketene-vinylimine cycloaddition they are equal to ca. 30-55 kcal/mol. All the reactions studied were found to be concerted and mostly asynchronous. Simulation of the solvent environment (toluene, tetrahydrofuran, acetonitrile, and water) by using Tomasi's polarized continuum model with the integral equation formalism (IEF-PCM) method showed the allene-isocyanic reactions remained concerted, yet the activation barriers were somewhat higher than those in the gas phase, whereas the ketene-vinylimine reactions became stepwise. The larger the solvent dielectric constant, the lower the activation barriers found. The lowest-energy pathways in the gas phase and in solvent were confirmed by intrinsic reaction coordinate (IRC) calculations. The atoms in molecules (AIM) analysis of the electron density distribution in the transition-state (TS) structures allowed us to distinguish pericyclic from pseudopericyclic from nonplanar-pseudopericyclic types of reactions.

The reaction paths of [2+2] cycloaddition of the X=C=Y cumulenes were modeled at the MP2/aug-cc-pVDZ level. Cycloadditions of allene and CO2, CS2, or OCS lead in part to the same four-membered products as dimerizations of either ketene or thioketene or addition of ketene and thioketene, respectively. All the reactions studied are concerted and mostly asynchronous. The majority of the allene cycloadditions studied are endoergic and proceed with much higher activation barriers than do the alternative (thio)ketene additions. In comparison with the energy of the substrates, the four-membered cycles incorporating S-atoms are stabilized more than the analogous structures with O-atoms built into the rings. There are also some products that are thermodynamically disfavored, yet seem to be obtainable thanks to a relatively low barrier of the reaction. The AIM analysis of the electron density distribution in the transition state structures allowed distinguishing pericyclic from pseudopericyclic and nonplanar-pseudopericyclic types of reaction.

The conformational landscape of phenylisoserine (PhIS) was studied. Trial structures were generated by allowing for all combinations of single-bond rotamers. Based on the B3LYP/aug-cc-pVDZ calculations 54 conformers were found to be stable in the gas phase. The six most stable conformers were further optimized at the B3LYP/aug-cc-pVTZ and MP2/aug-cc-pVDZ levels for which characteristic intramolecular hydrogen bond types were classified. To estimate the influence of water on PhIS conformation, the IEF-PCM/B3LYP/aug-cc-pVDZ calculations were carried out and showed 51 neutral and six zwitterionic conformers to be stable in water solution. According to DFT calculations, the conformer equilibrium in the gas phase is dominated by one conformer, whereas the MP2 calculations suggest three PhIS structures to be significantly populated. Comparison of DFT and MP2 energies of all 57 structures stable in water indicates that, in practice, one zwitterionic and one neutral conformer determine the equilibrium in water. Based on the AIM calculations, we found that for the neutral conformers in vacuum and in water, d(H...B) is linearly correlated with Laplacian at the H-bond critical point. Figure Phenylisoserine (PhIS) is an active side chain of cytotoxic Paclitaxel medicine. The conformational landscape of phenylisoserine was studied. One zwitterionic and one neutralconformer determine the equilibrium in water whereas in the gas phase the MP2 calculations suggest three PhIS structures to be significantly populated. Electronic supplementary material The online version of this article (doi:10.1007/s00894-010-0783-8) contains supplementary material, which is available to authorized users.