PCM Model Research Articles

Mechanism of the Pechmann Reaction: A Theoretical Study

One of the most widespread synthetic routes to coumarins is the condensation of esters and phenols via the Pechmann reaction. Despite the industrial and technological importance of the reaction, its mechanism is still poorly understood. We have explored several possible reaction paths by DFT calculations at the M05-2X/6-31+G* level. Amphoteric groups and the solvent have a crucial role in the frequent proton-transfer steps of the mechanisms; therefore, we have employed a mixed solvent model, where we combined the implicit PCM model together with an explicit water molecule placed at the actual proton transfer region. The Gibbs free-energy profiles of the possible routes suggest that three parallel channels (featuring water elimination, trans-esterification, and electrophilic attack) operate simultaneously. Enolic routes have prohibitively high activation barriers rendering these paths untenable. The calculated profiles indicate that in each feasible route the first elementary step has the highest activation energy. Reaction intermediates identified on the free-energy profiles can explain several experimental observations.

Effect of solvent polarity on photophysical parameters of 3-aminoflavone

Photophysical behavior of 3-amino flavone (3AF) in different media has been studied using steady state and time-resolved fluorescence spectroscopy in combination with DFT and TD DFT B3LYP/6-31G (d,p) calculations involving the ground and the excited state geometry optimization. Comparison of experimental solvatochromic shifts with the calculated energies in different solvents (PCM model) allows to conclude that the excited state of 3AF, corresponding to the π → π* ( S 0 → S 1) transition, has a partial CT nature. The lifetime and quantum efficiency measurements in function of solvent polarity shown that in weakly polar solvents the radiationless rate constant is very high. On the basis of TD DFT calculations for singlet and triplet state distribution in different environments (PCM model) we hypothesize that in weakly polar solvents the intersystem crossing may be a prevailing relaxation process.

Theoretical Investigation of Solvation Effects on the Tautomerism of Maleic Hydrazide

A DFT study is used to calculate structural data of tautomers of maleic hydrazide (MH) in the gas phase and selected solvents such as benzene (non‐polar solvent), tetrahydrofuran (polar aprotic solvent) and methanol (protic solvent), dimethyl sulfoxide (polar aprotic solvent) and water (protic solvent) using PCM model. All tautomers are optimized at the B3LYP/6−31++G(d,p). The results show that the tautomer MH2except in methanol is more stable than the other tautomers but in methanol MH5 (Diol) is more stable. In addition, stability of the tautomers in deferent solvents shows interesting results. Variation of dipole moments and NBO charges on atoms in the solvents were studied.

Computational Model for Predicting Experimental RNA and DNA Nearest-Neighbor Free Energy Rankings

Hydrogen-bonding, intrastrand base-stacking, and interstrand base-stacking energies were calculated for RNA and DNA dimers at the MP2(full)/6-311G** level of theory. Standard A-form RNA and B-form DNA geometries from average fiber diffraction data were employed for all base monomer and dimer geometries, and all dimer binding energies were obtained via single-point calculations. The effects of water solvation were considered using the PCM model. The resulting dimer binding energies were used to calculate the 10 unique RNA and 10 unique DNA computational nearest-neighbor energies, and the ranking of these computational nearest neighbor energies are in excellent agreement with the ranking of the experimental nearest-neighbor free energies. These results dispel the notion that average fiber diffraction geometries are insufficient for calculating RNA and DNA stacking energies.

Evaluation of future hydrological cycle under climate change scenarios in a mesoscale Alpine watershed of Italy

Abstract. We investigate future (2045–2054) hydrological cycle of the snow fed Oglio (≈1800 km2) Alpine watershed in Northern Italy. A Stochastic Space Random Cascade (SSRC) approach is used to downscale future precipitation from three general circulation models, GCMs (PCM, CCSM3, and HadCM3) available within the IPCC's data base and chosen for this purpose based upon previous studies. We then downscale temperature output from the GCMs to obtain temperature fields for the area. We also consider a projected scenario based upon trends locally observed in former studies, LOC scenario. Then, we feed the downscaled fields to a minimal hydrological model to build future hydrological scenarios. We provide projected flow duration curves and selected flow descriptors, giving indication of expected modified (against control run for 1990–1999) regime of low flows and droughts and flood hazard, and thus evaluate modified peak floods regime through indexed flood. We then assess the degree of uncertainty, or spread, of the projected water resources scenarios by feeding the hydrological model with ensembles projections consistent with our deterministic (GCMs + LOC) scenarios, and we evaluate the significance of the projected flow variables against those observed in the control run. The climate scenarios from the adopted GCMs differ greatly from one another with respect to projected precipitation amount and temperature regimes, and so do the projected hydrological scenarios. A relatively good agreement is found upon prospective shrinkage and shorter duration of the seasonal snow cover due to increased temperature patterns, and upon prospective increase of hydrological losses, i.e. evapotranspiration, for the same reason. However, precipitation patterns are less consistent, because HadCM3 and PCM models project noticeably increased precipitation for 2045–2054, whereas CCSM3 provides decreased precipitation patterns therein. The LOC scenario instead displays unchanged precipitation. The ensemble simulations indicate that several projected flow variables under the considered scenarios are significantly different from their control run counterparts, and also that snow cover seems to significantly decrease in duration and depth. The proposed hydrological scenarios eventually provide a what-if analysis, giving a broad view of the possible expected impacts of climate change within the Italian Alps, necessary to trigger the discussion about future adaptation strategies.

Thermodynamics of boroxine formation from the aliphatic boronic acid monomers R-B(OH)2 (R = H, H3C, H2N, HO, and F): a computational investigation.

Boroxines are the six-membered cyclotrimeric dehydration products of organoboronic acids, 3R–B(OH)2 → R3B3O3 + 3H2O, and in recent years have emerged as a useful class of organoboron molecules with applications in organic synthesis both as reagents and catalysts, as structural components in boronic-acid-derived pharmaceutical agents, and as anion acceptors and electrolyte additives for battery materials [Korich, A. L.; Iovine, P. M. Dalton Trans. 2010, 39, 1423−1431]. Second-order Møller–Plesset perturbation theory, in conjunction with the Dunning–Woon correlation-consistent cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, and aug-cc-pVTZ basis sets, was used to investigate the structures and relative energies of the endo–exo, anti, and syn conformers of the aliphatic boronic acids R–B(OH)2 (R = H, H3C, H2N, HO, and F), as well as the thermodynamics of their boroxine formation; single-point calculations at the MP2/aug-cc-pVQZ, MP2/aug-cc-pV5Z, and CCSD(T)/aug-cc-pVTZ levels using the MP2/aug-cc-pVTZ optimized geometries were also performed in selected cases. The endo–exo conformer was generally lowest in energy in vacuo, as well as in PCM and CPCM models of aqueous and carbon tetrachloride media. The values of ΔH(298)(0) for boroxine formation via dehydration from the endo–exo conformers of these aliphatic boronic acids ranged from −2.9 for (H2N)3B3O3 to +12.2 kcal/mol for H3B3O3 at the MP2/aug-cc-pVTZ level in vacuo; for H3B3O3, the corresponding values in PCM/UFF implicit carbon tetrachloride and aqueous media were +11.2 and +9.8 kcal/mol, respectively. On the basis of our calculations, we recommend that ΔHf(298K) for boroxine listed in the JANAF compilation needs to be revised from −290.0 to approximately −277.0 kcal/mol.

DFT/TDDFT investigation of the electronic structures and optoelectronic properties of phosphorescent iridium (III) complexes with non-conjugated cyclometalated carbene ligands

This work investigates the electronic structures and spectroscopic properties of several cyclometalated iridium carbene complexes possessing at least one functionalized methylene moiety, (dfpmb)(dfbmb)Ir(mptz) (2), (dfbmb)2Ir(mptz) (3), and (dfbmb)2Ir(mpmtz) (4) (dfpmbH =1-difluorophenyl-3-methyl-benzimidazoline-2-ylidene; dfbmbH = 1-(2,4-difluorobenzyl)-3-(methylbenzimidazolium; mptzH = 4-methyl-2-(5-(trifluoromethyl)-2H-1,2,4-triazol-3-yl)pyridine); mpmtzH = 4-methyl-2-(3-methylene-5-(trifluoromethyl)- 2H-1,2,4-triazole-3-yl)pyridine) on the basis of their prototype (dfpmb)2Ir(mptz) (1) via DFT and TDDFT methods. A careful examination of results shows: (1) the patterns of the occupied orbitals for 1–4 are almost the same, with the HOMO being an admixture of the Ir atom and benzyl part, whereas the LUMO is predominately delocalized over the ancillary chelate mptz or mpmtz; (2) complexes 1–3, and especially 4, all exhibit blue emission with maximum wavelengths at 506, 495, 486, and 478 nm, respectively; (3) complex 4 with the highest (relative) component of 3MLCT can be reasonably expected to have a higher radiative transition rate constant (kr ) among 1–4. From the highest absorption peaks, eventually, the molar extinction coefficient discrepancy between experiment and calculations might be tentatively attributable to the synergism of the intrinsic imperfection of the PCM model and the simplification of chemical computations.

A DFT study of the enantioselective reduction of oxime ethers promoted by chiral spiroborate esters

AbstractMechanisms of borane reduction of the (E)‐acetophenone O‐methyl oxime catalyzed by the easily prepared and stable spiroborate ester 1, derived from diphenylvalinol has been reported for the first time using density functional theory. Two reaction pathways are investigated at the B3LYP/6‐31G(d,p) level of theory. The calculated results reveal that this reaction is accomplished via four steps. All the reactants, products, transition states, and intermediates have been optimized at the B3LYP/6‐31G (d,p) level. The analysis of these results reveals that one pathway is more energetically favorable than the other, and its associated product is in good agreement with the experimental result. The solvent effect has been further considered at the B3LYP/6‐31G(d,p) level in the solvent THF using the PCM model, and the results indicate that it has no great influence on the enantioselectivity of this reduction. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012

Theoretical investigation of one- and two-photon spectra of pyrazabole chromophores

An extensive series of pyrazabole chromophores containing pseudo-conjugated systems have been theoretically constructed and investigated on the one-photon absorption (OPA) and two-photon absorption (TPA) properties by using density functional theory and Zerner’s intermediate neglect of differential overlap methods. The results indicated that all the pyrazabole chromophores show strong OPA at around 400 nm and intense TPA properties in the range of 500–600 nm with TPA cross sections (δ max) as large as 540–3,560 GM, which are excellent candidates for optical power limiting materials. It is noteworthy that the δ max values of the two constructed pyrazaboles, PA3 and PAF2, are 308.8 GM at 772.0 nm and 157.8 GM at 834.4 nm, respectively, which may be particularly attractive as probes for two-photon fluorescence imaging. The influence of incorporating electron acceptors in the central core, π-conjugated bridge and terminal groups on OPA and TPA properties was analyzed in detail to derive structure–property relationships and to lay the guidelines for both spectral tuning and amplification of molecular TPA in the target region. Meanwhile, the solvent effects on these properties were taken into account within the PCM model. The solvent has a significant impact on the TPA properties for chromophore PA3 and leads to the two-photon absorption spectra (λ max ) red-shift and δ max enhancing relative to those in gas phase. In addition, from the calculations of molecule AlA2, we can draw the conclusion that the compounds with the Al2N4 center behave similarly to pyrazabole chromophores in the linear optical and TPA properties and increase TPA cross sections to some extent.

Electronic, optical and charge transfer properties of α,α′-bis(dithieno[3,2- b:2′,3′- d]thiophene) (BDT) and its heteroatom-substituted analogues

The ground state geometry of α,α′-bis(dithieno[3,2- b:2′,3′- d]thiophene) (BDT) and its heteroatom-substituted analogues have been optimized using B3LYP/6-31G ∗∗ and PBE0/6-31G ∗∗ level of theories. The absorption spectra have been computed in the presence and absence of solvent at PCM and CPCM models. The designed analogues where sulfur was substituted by NH (NHBDT), oxygen (OBDT) are blue shifted while BH substituted one (BHBDT) is red shifted. The vertical ionization potentials of NHBDT and OBDT are comparatively smaller than BDT revealing that injection barrier for hole would be small. The calculated vertical electronic affinity of BHBDT is 3.32 eV while its vertical ionization potential is 6.53 eV. Balanced hole and electron reorganization energies predicted that it would be good ambipolar material.

Half rotations leading to retention of stereochemistry in epoxide ring opening by selenocyanate ion: Insights from DFT modeling

Stilbene oxide on reaction with selenocyanate ion in methanol (Culvenor et al., J Chem Soc 1949, 278) has been found to yield the corresponding stilbene with the deposition of metallic Se. For this reaction, a tentative mechanism involving “two half rotations” around the carbon–carbon bond based on the observed stereospecificity and formation of episelenide intermediate has been suggested. This reaction has been modeled at B3LYP/6-31+G(d) level and the potential energy surface of the reaction has been explored. Computations suggest a backside attack of the selenocyanate ion to one of the epoxide carbon atoms to form a prereactive complex, two successive half-rotations around the carbon–carbon bond in the opposite direction, the formation and decomposition of episelenide intermediate, and finally trans-stilbene. Calculations besides agreeing excellently with experiment reveal many interesting mechanistic details that experimentalists could not unravel. Wiberg bond order analyses reveal the smooth progress in the bond changes during the course of the reaction. Solvent effect through PCM model calculations with methanol as solvent does not alter the gas phase results significantly. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011

Reaction Mechanism and Chemoselectivity of Intermolecular Cycloaddition Reactions between Phenyl-Substituted Cyclopropenone Ketal and Methyl Vinyl Ketone

In this paper, the mechanisms of the intermolecular [3+2] and [1+2] cycloaddition reactions of 1,1/1,3-dipolar π-delocalized singlet vinylcarbenes, which is obtained from cyclopropenone, with an electron-deficient C═O or C═C dipolarophile, to generate five-membered ring products are first disclosed by the density functional theory (DFT). Four reaction pathways, including two concerted [3+2] cycloaddition reaction pathways and two stepwise reaction pathways (an initial [1+2] cycloaddition and then a rearrangement from the [1+2] cycloadducts to the final [3+2] cycloadducts), are investigated at the B3LYP/6-31G(d,p) level of theory. The calculated results reveal that, in contrast to the concerted C═O [3+2] cycloaddition reaction pathway, which is 7.1 kcal/mol more energetically preferred compared with its stepwise reaction pathway, the C═C dipolarophile favors undergoing [1+2] cycloaddition rather than concerted [3+2] cycloaddition (difference of 5.3 kcal/mol). The lowest free energy barrier of the C═O concerted [3+2] cycloaddition reaction pathway shows that it predominates all other reaction pathways. This observation is consistent with the finding that the C═O [3 + 2] cycloadduct is the main product under experimental conditions. In addition, natural bond orbital second-order perturbation charge analyses are carried out to explain the preferred chemoselectivity of C═O to the C═C dipolarophile and the origins of cis-stereoselectivity for C═C [1+2] cycloaddition. Solvent effects are further considered at the B3LYP/6-31G(d,p) level in the solvents CH(3)CN, DMF, THF, CH(2)Cl(2), toluene, and benzene using the PCM model. The results indicate that the relative reaction trends and the main products are insensitive to the polarity of the reaction solvent.

Theoretical study of the neutral hydrolysis of methyl formate via a concerted and stepwise water-assisted mechanism using free-energy curves and molecular dynamics simulation

A procedure previously described by us is used for the theoretical study of chemical reactions in solution by means of molecular dynamics simulation, with solute–solvent interaction potentials LJ (12-6-1) derived from ab initio quantum calculations. We apply the procedure to the case of the neutral hydrolysis of methyl formate, HCOOCH3 + 3H2O → HCOOH + CH3OH + 2H2O in aqueous solution, via concerted and stepwise water-assisted mechanisms. We use the solvent as reaction coordinate, and the free-energy curves for the calculation of the activation energies. The theoretical calculation for the thermodynamics of this hydrolysis reaction in aqueous solution, assisted by three water molecules, is in agreement with the available experimental information. In particular our study gives values of ΔG ≠ = 28.88 and 28.17 kcal/mol for the concerted and stepwise mechanisms, close to the experimental activation barrier of 28.8 kcal/mol, and a significant improvement over the values of 48.05 and 45.66 kcal/mol found in another similar study using the PCM model.

Conformational analysis of 4,4-dimethyl-4-silathiane and its S-oxides

4,4-Dimethyl-4-silathiane and its S-oxides [n = 0 (1), 1 (2), 2 (3)] were studied experimentally by variable temperature dynamic NMR spectroscopy down to 103 K and the frozen ring inversion was revealed for all three compounds. The barriers for the degenerate ring inversion in 1 and 3 were measured to be 4.8 and 5.0 kcal/mol at the coalescence temperatures of 111 and 116 K, respectively, and practically coincide with the calculated barriers of 4.60 kcal/mol in 1 and 4.46 kcal/mol in 3. The frozen equilibrium mixture 2-ax/2-eq contains 37% of the 2-ax and 63% of the 2-eq conformer. The ring inversion barrier proved to be ca. 4.8 kcal/mol. Calculations at the B3LYP/6-311+G(d,p) level of theory showed the 2-ax conformer to be 0.90 kcal/mol more stable than the 2-eq conformer in the gas phase whereas in solution the relative stability of the conformers calculated using the PCM model at the same level of theory is inverted to become 0.19 (in CHCl3) or 0.36 kcal/mol (in DMSO) in favor of the 2-eq conformer. The chair–chair interconversion mechanism of sulfoxide 2 includes two intermediate energetically equivalent 1,4-twist forms and the 2,5-boat transition state: 2-ax (chair) ⇆ 2 (1,4-twist) ⇆ [2 (2,5-boat)]≠ ⇆ 2 (1,4-twist) ⇆ 2-eq (chair). The calculated ring inversion barriers are 5.1 (2-ax → 2-eq) and 4.2 kcal/mol (2-eq → 2-ax) in the gas phase, and 4.03 and 4.22 kcal/mol, respectively, in chloroform. Copyright © 2011 John Wiley & Sons, Ltd.

A Computational Study on the Chemical Fixation of Carbon Dioxide with Epoxide Catalyzed by LiBr Salt

The chemical fixation of carbon dioxide with 2,3-epoxypropyl phenyl ether catalyzed by LiBr salt to produce a five-membered cyclic carbonate, 4-(phenoxymethyl)-1,3-dioxolan-2-one, has been extensively investigated at the B3LYP density functional level of theory. The solvent effects have been studied by means of a PCM model. All possible pathways are examined, and their corresponding energetics are demonstrated. Our results reveal that the overall reaction comprises three main steps: epoxide ring-opening, carbon dioxide insertion, and ring-closure of cyclic carbonate, none of which contains significantly large barriers. On the basis of the computed free energies of activation, the rate-determining step can be the ring-opening of epoxide or the ring-closure of cyclic carbonate with variation in the reaction conditions in N-methylpyrrolidinone (NMP) solvent. Our calculations indicate that path 2 is more favorable than path 1 in the gas phase, while both of them exist possibly in NMP solvent. The overall reaction is exothermic. Furthermore, the free energy profiles of all reaction pathways along the minima energy path in the gas phase and in NMP solvent were obtained and compared. It is shown that NMP solvent does not change the general trends for the reaction potential energy surfaces.

Evidence for the Role of Tetramethylethylenediamine in Aqueous Negishi Cross-Coupling: Synthesis of Nonproteinogenic Phenylalanine Derivatives on Water

The structure of the alkylzinc-tetramethylethyl-enediamine (TMEDA) cluster cation 3 has been determined in the gas phase by a combination of tandem mass spectrometry, infrared multiphoton dissociation (IRMPD) spectroscopy, and DFT calculations. Both sets of experimental results establish the existence of a strongly stabilizing interaction of TMEDA with the zinc cation. High-level DFT calculations on the alkylzinc-TMEDA cluster cation 3 allowed the identification of two low energy conformers, each featuring a four-coordinate zinc atom with a bidentate TMEDA ligand, and internal coordination from the carbonyl group of the Boc group to zinc. The experimental IRMPD spectrum is reproduced with an appropriately weighted combination of the IR spectra of the two conformers identified by theory. DFT calculations on the structure of the alkylzinc halide 2 with coordinated TMEDA using the PCM model of water solvent suggest that TMEDA can promote ionization of the zinc-iodine bond in organozinc iodides under aqueous conditions, providing a credible explanation for the role of TMEDA in stabilizing the carbon-zinc bond. Reaction of the serine-derived iodide 1 with aryl iodides "on water", promoted by nano zinc in the presence of PdCl(2)(Amphos)(2) (5 mol %) and TMEDA, leads to the formation of protected phenylalanine derivatives 4 in reasonable yields. In the case of ortho-substituted aryl iodides and aryl iodides that are solids at room temperature, conducting the reaction at 65 °C gives improved results. In all cases, the product 5 of reductive dimerization of the iodide 1 is also isolated.

Chemical Reactivity of Atrazine Employing the Fukui Function

In the present work we calculated reactivity descriptors for atrazine at MP2/6-311++G(2d,2p)//B3LYP/6-311++G(2d,2p) level in order to analyze its reactivity. Reactivity descriptors such as ioniza- tion energy, molecular hardness, electrophilicity, condensed Fukui function and total energies were determined to identify changes in the reactivity of atrazine in the gas and aqueous phases. The influence of the solvent was taken into account with the PCM model. The values of the reactivity descriptors indicated that the interaction of atrazine with water diminished its reactivity in comparison with the exhibited in gas phase. Also, it was found that the electrophilic and free radical attacks were equivalent and they were located on all the cases in the ethylamine and isopropylamine groups.

Substituent effects on BTP's basicity and complexation properties with LnIIIlanthanide ions

Bis(1,2-4 triazin-3-yl)pyridines “BTPs” represent a new class of N-donor extracting agents that separate trivalent actinides and lanthanides from nuclear waste solutions with high An/Ln separation factors. We report here QM calculations on the effect of Rpara–BTP substituents on the protonation and complexation energies of these ligands (1 ∶ 1 and 1 ∶ 3 complexes with LnIII lanthanides) in the gas phase. Both processes follow similar trends and are highly sensitive to the electron donor/acceptor character and polarizability of R. When compared to R–pyr analogues with pyridine, R–BTPs are found to be intrinsically much more basic, by ca. 20 kcal mol−1. In aqueous solution, however (modelled by the continuum PCM model), BTPs and pyridines have a similar basicity, pointing to the importance of solvent environment on their protonation states. In the optimized Ln(R–BTP)33+ complexes with Ln = La, Eu, Yb, complexation energies Ec3 increase with the intrinsic basicity of the ligands, in the order R = NMe2 > NH2 > OMe > C6H5 > tButyl > Me > H > F > Cl. Furthermore, comparison of complexes with different LnIII cations indicates that their stability increases in the order LaIII < EuIII < YbIII, by the same amount with the different R-substituents. The relative contributions of central pyridinyl and lateral triazinyl nitrogens of BTPs are shown to depend on the stoichiometry of the complex and on the LnIII size, possibly contributing to the subtle AnIII/LnIII discrimination by substituted BTPs.

Conformational analysis, tautomerization, IR, Raman, and NMR studies of benzyl acetoacetate

A complete conformational analysis of the keto and enol forms of benzyl acetoacetate (BAA), a β-dicarbonyl compound, was carried out by ab initio calculations, at the density functional theory (DFT) level. By inspection of all possible conformers and tautomers, 22 stable cis-enol, 28 stable trans-enol, and five keto conformers were obtained. Among all stable cis-enol forms only six of them are engaged in intramolecular hydrogen bond. The hydrogen bond strength of the most stable conformer of BAA is compared with that of acetylacetone (AA) and dimethyl oxaloacetate (DMOA). Harmonic vibrational frequencies of the most stable enol and keto forms and their deuterated analogues were also calculated and compared with the experimental data. According to the theoretical calculations, the hydrogen bond strength of the most stable enol conformer of BAA is 56.7 kJ/mol (calculated at the B3LYP/6-311++G ∗∗ level), about 10 kJ/mol less than that of AA. This weakening of hydrogen bond is consistent with the spectroscopic results. NMR studies indicate that BAA exists mainly as a keto tautomer in all considered solutions. The Gibbs energies for keto/enol tautomerization were calculated at the B3LYP level, with several basis sets, in both gas phase and CH 3CN solution (using PCM model), for the most stable enol and keto conformers.

Phosphonic drugs: Experimental and theoretical spectroscopic studies of fosfomycin

pH and time-dependant changes of fosfomycin molecular structure in an aqueous solution are studied by Raman, NMR, and generalized 2D correlation spectroscopies. Interpretation of the experimental spectra is based on the assumption of formation of different species running on applied physicochemical conditions. Geometries of all possible structures were entirely optimized with the 6-311++G(2df,p) basis set at the B3LYP theoretical level using procedures implemented in the Gaussian ’03 set of programs. Harmonic frequency calculations verified the nature of the studied structures and allowed to simulate obtained Raman spectra. The theoretical NMR shielding was calculated using the GIAO method at the same computational level. In addition, in some cases PCM model was used to monitor the influence of water molecules on the NMR spectra. It is shown that in the pH range of 1–2 of fosfomycin aqueous solution oxirane ring is open sequent to nucleophilic attack and forms 1,2-dihydroxyphosphonic acid with small content of its monodeprotonated species. On the other hand, in pH 7 and higher it appears either as 1,2-epoxypropylphosphonic or 1,2-dihydroxyphosphonic dianion depending upon whether hydrolysis took place or not. It is also discussed that Raman marker bands originating from the individual species of fosfomycin can be used to detect and/or to monitor this antibiotic in an aqueous medium (for example urine samples). Hence, depending upon the structure found in urine one can tell about metabolic processes of this antibiotic in the body.