A presente tese relata a síntese e a análise conformacional das: N-metóxi-N-metil- 2-feniltiopropanamidas 4\'-substituídas (I), N-metóxi-N-metil-2- fenilssulfinilpropanamidas 4\'-substituídas (II) e N-metóxi-N-metil-2- fenilssulfonilpropanamidas 4\'-substituídas (III), através da espectroscopia no Infravermelho na região da banda da carbonila (vco), apoiada por cálculos teóricos. A análise conformacional de (I) indicou, através de dados de DFT/cc-pVDZ a existência de um equilíbrio entre duas conformações gauche devido à ocorrência de uma forte interação orbitalar estabilizante π*co/σc-s nas mesmas. A série dos derivados sulfinilados (II) apresentou-se como um par de diastereoisômeros. A análise conformacional para o diast1 (par enantiomérico CRSS/CSSR), através do cálculo HF/6-31G** e IV, indicou a existência de um equilíbrio conformacional entre dois confôrmeros quasi-cis (q-c1 e q-c2) e outro gauche (g), sendo os confôrmeros quasi-cis (q-c1 e q-c2) mais estáveis devido à interação de transferência de carga Oσ-(CO)→Sσ+SO mais intensa do que a interação Oσ-(SO)→Cσ+CO presente no confôrmero gauche (g). A análise para o diast2 utilizando-se o cálculo HF/6-31G** indicou a presença dos confôrmeros quasi-gauche (q-g), e quasi-cis (q-c3) sendo o primeiro mais estável no estado gasoso por apresentar uma interação transferência de carga cruzada Oσ-(CO)→Sσ+SO e Oσ-(SO)→Cσ+CO. Os dados de cálculo HF/6-31G** para os derivados sulfonilados (III) indicaram um equilíbrio conformacional entre duas conformações gauche (g1 e g2) decorrente de uma interação Coulômbica e de transferência de carga cruzada Oδ-(SO2)→Cδ+CO e Oδ-(CO)→Sδ+SO2. A presente Tese também relata a obtenção de compostos ß-lactâmicos acilados no carbono C3 e C4. As N-metóxi-N-metil-2-feniltiopropanamidas-4\'-substituídas (I) agem como acilantes do anel ß-lactâmico (N-fenil-2-azetidinona) para obtenção dos derivados ß-lactâmico C3 acilados. A reação foi realizada com sucesso, contudo, a purificação dos compostos alvo não se mostrou eficaz obtendo-se apenas as 3-[2- (4\'-feniltio)propanoil]-N-fenil- e 3-[2-(4\'- clorofeniltio)propanoil]-N-fenil-2-azetidinonas através de um processo de cristalização. Para a obtenção dos derivados ß-lactâmicos C4 acilados utilizou-se a N-metóxi-N-metil-4-oxo-1-fenilazetidina-2- carboxamida como acilante dos carbânions derivados de 4\'-fenilmetilssulfóxidos [4\'-YPhS(O)CH3 Y= OMe, Me, H]. Esta reação forneceu as 1-fenil- (4-fenilssulfinilacetil- 3 4\'-substituídos)-2-azetidinonas correspondentes com bons rendimentos. A redução destas azetidinonas-sulfóxidos forneceu as azetidinonas-sulfetos correspondentes também com bons rendimentos / This thesis reports the synthesis and the conformational analysis of: N-methoxy-N- methyl-2-[(4\'-substituted)-phenylthio]-propanamides (I), N-methoxy-N-methyl-2-[(4\'- substituted)-phenylsulfinyl]-propanamides (II) and N-methoxy- N-methyl-2-[(4\'- substituted)-phenylsulfonyl]-propanamides (III) by Infrared spectroscopy through the analysis of the carbonyl stretching band supported by theoretical calculations. The conformational analysis of (I) through DFT computations have indicated the equilibrium of two gauche conformations due to a strong stabilizing π*co/σc-s orbital interaction. The group of sulfinyl derivatives (II) exist as a diastereomeric pair. The conformational analysis of diast1 (enantiomeric pair CRSS/CSSR) through IR and HF/6-31G** has shown the existence of an equilibrium between two quasi-cis (q-c1 and q-c2) and one gauche (g) conformers, being the quasi-cis conformers the more stable ones due to the Oσ-(CO)→Sσ+SO charge transfer interaction which in turn is stronger than the Oσ-(SO)→Cσ+CO orbital interaction which takes place in the gauche (g) conformer. As for diast2 the HF/6-31G** computations along IR data has indicated 2 the occurrence of the quasi-gauche (q-g) and quasi-cis (q-c ) conformers, being the former the more stable one in gaseous phase due to the Oσ-(CO)→Sσ+SO e Oσ-(SO)→Sσ+CO crossed charge transfer. The HF/6-31G** and vco data for the sulfonylated derivatives (III) have shown the existence of the equilibrium between two gauche (g1 and g2) conformations which are stabilized through Oδ-(SO2)→Cδ+CO and Oδ-(CO)→Sδ+SO2 electrostatic and charge transfer interactions. This Thesis also deals with the preparation of some C3 and C4 acylated ß-lactamic compounds. The N-methoxy- N-methyl-2-[(4\'-substituted)-phenylthio-propanamides (I) act as acylating agents of the ß-lactamic ring (N-phenyl-2-azetidinone) in order to obtain the C-3 acylated ß-lactamic derivatives. These reactions gave the target products contaminated with starting material in good yields except for the 3-[2- (4\'phenylthio)propanoyl]-N-phenyl- and 3-[2-(4\'-chlorophenylthio)propanoyl]-N- phenyl-2-azetidinones which were obtained in pure form after crystallization. As for the C-3 acylated ß-lactamic derivatives they were obtained from the reaction of N-methoxy-N-methyl-4-oxo-1-phenylazetidine-2-carboxamide and the appropriate carbanions of 4\'-substituted phenylmethylsulfoxides. This reaction gave the corresponding 1-phenyl- (4-substituted-phenylsulfinylacetyl)-2-azetidinones in good yields. The corresponding azetidinone-sulfides were obtained from the reduction of the azetidinone-sulfoxides.

Orientador: Roberto Rittner / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-11T06:54:29Z (GMT). No. of bitstreams: 1 daSilva_JulioCesarAraujo_M.pdf: 2287772 bytes, checksum: ee8613d61a9f9feb9fa6894b5197e36f (MD5) Previous issue date: 2008 / Resumo: Neste trabalho é apresentado o estudo conformacional dos agonistas muscarinicos da acetilcolina (ACh+): carbacol, metacolina e pilocarpina. O estudo baseou-se na análise das constantes de acoplamento 3JHH e nos dados obtidos pelos cálculos teóricos ab initio. O comportamento conformacional destes compostos é descrito principalmente por apenas dois dos seus ângulos diedros. Os resultados dos cálculos teóricos realizados com o nível teórico B3LYP/6- 311+G(d,p), bem como os dados experimentais, apontaram a conformação gauche como a predominante para todos os compostos estudados para o diedro responsável pela atividade farmacológica dos agonistas independente do solvente utilizado. Atribui-se a estabilização da forma gauche a interação eletrostática entre o atomo de nitrogênio positivamente carregado e o átomo de oxigênio da porção éster (OCH2). Os cálculos teóricos mostraram que os conformeros mais estáveis possuem uma distância N+/O menor. Em adição, estudos de NBO mostraram a importância das interações hiperconjugativas sC5H5 s* C6N7 e sC5H5s* O4C5 na maior estabilização dos conformeros gauche. Os conformeros mais estáveis para cada composto sao: aceticolina, TG-; carbacol, AG+; metacolina, TG+; pilocarpina, TG+C / Abstract: This work describes the conformational analysis of muscarine agonists of acetylcholine (ACh+): carbachol, metacholine and pilocarpine. It was performed from the analysis of 3JHH coupling constants and from ab initio theoretical calculations. Their conformational behavior is discussed taking into account the most important dihedral angles. Both the results from theoretical calculations at B3LYP/6-311+G(d,p) as the experimental data indicated that the gauche conformer is predominant, considering the dihedral angle wich is responsible by their pharmacological activity regardless the solvente employed. The stabilization of the gauche conformer was ascribed to the eletrostatic interaction between the positively charged nitrogen atom and the (OCH2) oxygen atom of the ester fragment. This was confirmed by the N+/O smaller distance for the most stable conformers. In addition, NBO data showed the relevant role of sC5H5 s* C6N7 e sC5H5s* O4C5 hyperconjugative interactions of the gauche conformers. The most stable conformers for the above compounds are: : acetycholine, TG-; carbachol, AG+; methacholine, TG+; pilocarpine, TG+C / Mestrado / Quimica Organica / Mestre em Química

Orientador: Rogerio Custodio / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-11T20:32:26Z (GMT). No. of bitstreams: 1 Souza_KelyFerreirade_M.pdf: 2708513 bytes, checksum: 018efeaf228676a57ca3b884dc55ca80 (MD5) Previous issue date: 2008 / Resumo: Piroxicam é um fármaco com atividade analgésica, antiinflamatória e antipirética de uso muito difundido. Apresenta algumas reações adversas, dentre as quais a possibilidade de foto-sensibilidade cutânea após exposição do paciente à radiação solar. Por este motivo, o fármaco tem sido alvo de inúmeros estudos, mas até os dias atuais não se conhece o mecanismo envolvido na foto-sensibilidade. Com o objetivo de buscar maiores informações sobre o fármaco, o presente trabalho partiu de estudos preliminares tanto da forma ceto quanto da enólica, através do método AM1. Os resultados, em conjunto com dados experimentais, apontaram para o Piroxicam enol como principal tautômero envolvido nos mecanismos de foto-toxicidade. Construiu-se então uma superfície de potencial para o Piroxicam enol, agora com o método DFT/B3LYP/CEP-31G(d,p). Estudaram-se as barreiras de interconversão entre os confôrmeros mais estáveis através do método QST2. Calculou-se o espectro eletrônico destas espécies empregando o método TD-DFT/B3LYP/CEP-31G(d,p) utilizando-se o modelo PCM para inclusão do efeito de solvente. De posse do confôrmero de maior interesse, partiu-se para o estudo de uma proposta de mecanismo obtida da literatura para a reação entre o Piroxicam enol e a molécula de oxigênio no primeiro estado excitado singlete. Partindo-se da otimização em DFT/B3LYP/CEP-31G(d,p) das geometrias das espécies envolvidas no mecanismo, realizou-se a busca por estados de transição entre as mesmas através dos métodos QST2 e QST3. Estruturas de transição entre os caminhos testados foram obtidas, mostrando a possibilidade do mecanismo ocorrer. Os resultados do trabalho apontam, ainda, para um dos confôrmeros como o mais provável de se envolver em foto-reações / Abstract: Piroxicam is a widely used drug with analgesic, antiinflamatory and antipiretic properties. Undesirable side effects are observed in some patients, among which the photosensitivity skin after exposure to solar radiation. For that reason the drug has been widely studied, but until the present days the mechanism involved in the photosensitivity is still unknown. Looking for more information about the drug, preliminary studies were carried out on two tautomers of Piroxicam ¿ ceto and enol structures, using the AM1 method. The calculated and experimental data suggest that Piroxicam Enol is the main tautomer involved in the phototoxicity mechanisms. A new potential surface, now using the DFT/B3LYP/CEP- 31G(d,p) method, was calculated. The interconversion barriers were studied using the QST2 method. The electronic spectrum was calculated with the TD-DFT/B3LYP/CEP- 31G(d,p) method and the solvent effect was investigated applying the PCM model. The predominant conformer was studied in combination with the singlet excited oxygen molecule and a mechanism proposed in the literature was investigated. From the optimized geometries of the species involved in this mechanism, the transition states between them were studied using the QST2 and QST3 methods indicating a feasible reaction path. The results also show one of the conformers as the most important agent responsible by the photochemical sensitivity / Mestrado / Físico-Química / Mestre em Química

Orientador: Roberto Rittner / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-04T14:36:06Z (GMT). No. of bitstreams: 1 Mesquita_AlexandrePinto_M.pdf: 3953195 bytes, checksum: 418e539bcacd86a111fd5ab90fb668d9 (MD5) Previous issue date: 2005 / Mestrado / Quimica Organica / Mestre em Química

Orientador: Roberto Rittner Neto / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-04T16:43:04Z (GMT). No. of bitstreams: 1 Martins_CarinaRabelo_M.pdf: 2440804 bytes, checksum: 5902fcc19589dcc81792e0806f7ae9f6 (MD5) Previous issue date: 2005 / Resumo: Este trabalho apresenta estudos sobre o isomerismo conformacional das 2-halociclopentanonas (halo= cloro e bromo) utilizando a constante de acoplamento JHH, cálculos teóricos e a teoria de solvatação. Foi realizada a otimização das geometrias e das energias dos confôrmeros mais estáveis na forma C2 (meia cadeira) dos diferentes compostos, utilizando o programa Gaussian 98, sendo que a conformação mais estável obtida no vácuo foi a pseudo-axial para todos os compostos estudados. Os dados experimentais de JHH dos derivados clorado e bromado, juntamente com o resultado da otimização das geometrias e das energias nos níveis B3LYP e MP2 foram tratados computacionalmente pelos programas Models e BESTFIT, o que permitiu a análise do equilíbrio conformacional destes compostos em diferentes solventes. Os dados obtidos apontam para uma estabilização do confôrmero pseudo-equatorial (de maior momento de dipolo) de acordo com o aumento da polaridade do solvente, conforme o esperado. Estes resultados foram comparados aos resultados obtidos pela análise dos espectros de infravermelho, cujos resultados também mostram a estabilização do confôrmero pseudo-equatorial com o aumento da polaridade do meio. / Abstract: The present work reports an NMR metthod using the variation of the JHH coupling constants with the solvents, togethr with theoretical calculations and solvation theory for the conformational analysis of 2-halocyclopentanones (halo = chlorine and bromine). The results trom Ab initio calculations, performed with GAUSSIAN 98 program using DFT/B3LYP and MP2, showed that the theories for the chlorine and bromine-derivatives. The pseudo-axial half-chair (C2) form is stable, in vapour phase, for both compounds. The H NMR spectra were obtained in solvents of various polarities. The essential parameters for the solvation energy calculations were obtained through MODELS program using the optimized geometries trom Gaussian. The best values of intrinsic coupling constants tor each conformer and the experimental energy difference, in the vapour, phase were obtained through BESTFIT program, using the experimental coupling constants and data from theoretical calculations. These gave that the pseudo-equatorial conformer is stabilized with the increase in the solvent polarity. The results were complemented with data from infrared spectroscopy, which are in complete agreement with theoretical data. / Mestrado / Quimica Organica / Mestre em Química

Orientador: Roberto Rittner Neto / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-27T10:22:25Z (GMT). No. of bitstreams: 1 Duarte_ClaudimarJunker_D.pdf: 13121295 bytes, checksum: 3401d9f1581d3385c70c6c859f152c76 (MD5) Previous issue date: 2015 / Resumo: Neste trabalho, o equilíbrio conformacional de alguns ésteres metílicos de aminoácidos não acetilados (L-Serina, L-Treonina e L-Triptofano) e N-acetilados (Glicina, L-Alanina, L-Serina, L-Treonina e L-Triptofano) foi avaliado através de cálculos teóricos e técnicas experimentais de espectroscopia no Infravermelho e de RMN. A metodologia aplicada baseou-se em RMN de 1H (através do comportamento da constante de acoplamento spin-spin 3JHH) e deconvolução analítica do espectro de infravermelho na região de estiramento da carbonila. Os resultados obtidos foram utilizados para determinar a variação populacional de cada derivado de aminoácido em vários solventes. Além disso, cálculos teóricos em fase isolada e também considerando o efeito do solvente foram realizados para determinar os valores de 3JHH e a frequência de estiramento C=O. Os resultados calculados estão em boa concordância com os valores experimentais e proporcionam informações sobre o comportamento conformacional induzido por cada solvente. Adicionalmente, a análise dos Orbitais Naturais de Ligação e a Teoria Quântica dos Átomos em Moléculas foram empregadas para investigar a importância de efeitos clássicos e não clássicos sobre o equilíbrio conformacional dos sistemas supracitados. Diferente de várias propostas da literatura, foi demonstrado que efeitos estéricos e de hiperconjugação são interações importantes para o equilíbrio conformacional para o equilíbrio conformacional dos diversos derivados de aminoácidos avaliados, enquanto que ligações de hidrogênio apresentam contribuição secundária / Abstract: In this work, the conformational equilibrium of some methyl esters of amino acids non-acetylated (L-Serine, L-Threonine and L-Tryptophan) e N-acetylated (Glycine, L-Alanine, L-Serine, L-Threonine and L-Tryptophan) was evaluated by theoretical calculations and Infrared and 1H NMR spectroscopies. The applied methodology was based on the 1H NMR data (through the behavior of the 3JHH spin spin coupling constant) and analytical deconvolution of infrared spectra on the C=O stretching region. The obtained results were used to determine the populational variation of each amino acid derivative in several solvents. In addition, theoretical calculations in isolated phase and taking into account the solvent effect were carried out in order to obtain the values of 3JHH and C=O stretching vibration. The calculated results are in good agreement with the experimental data and provide insights into the conformational behavior induced by each solvent. Additionally, Natural Bond Orbital analysis and the Quantum Theory Atoms In Molecules were employed to investigate the importance of classic and non-classic effects over the conformational isomerism of aforementioned systems. In disagreement of several publications in the literature, it was found that steric effect and hyperconjugation are interactions important to conformational preferences of all amino acid derivatives evaluated whereas H-bonding plays a secondary role / Doutorado / Quimica Organica / Doutor em Ciências

No description available.

The Morita-Baylis-Hillman (MBH) reaction is a very versatile synthetic protocol to synthesize various useful compounds containing several functional groups. MBH acetates and carbonates are highly valued compounds as they have good potential to be precursors for organic synthesis reactions due to their ease of modification and synthesis. This thesis utilizes Density Functional Theory (DFT) calculations to understand the mechanism and selectivity of an unexpected tandem conjugate addition-elimination (CA-E) reaction of allylic alkylated Morita-Baylis-Hillman C- adducts. This synthetic protocol was developed by Prof. Zhi-Yong Jiang and co-workers from Henan University, China. The reaction required the use of sub-stoichiometric amounts of an organic or inorganic Brøndst base as a catalyst and was achieved with excellent yields (96%) in neat conditions. TBD gave the highest yield amongst the organocatalysts and Cs2CO3 gave the highest yield amongst all screened bases. A possible mechanistic pathway was proposed and three different energy profiles were modeled using 1,5,7-triaza-bicyclo-[4.4.0]-dec-5-ene (TBD), Cs2CO3 and CO32- as catalysts. All three models were able to explain the experimental observations, revealing both kinetic and thermodynamic factors influencing the selectivity of the CA-E reaction. CO32- model gave the most promising result, revealing a significant energy difference of 17.9 kcal/mol between the transition states of the two differing pathways and an energy difference of 20.9 kcal/mol between the two possible products. Although TBD modeling did not show significant difference in the transition states of the differing pathways, it revealed an unexpected secondary non-covalent electrostatic interaction, involving the electron deficient C atom of the triaza CN3 moiety of the TBD catalyst and the O atom of a neighboring NO2- group in the intermediate. Subsequent modeling using a similar substrate proved the possibility of this non-covalent electrostatic interaction, as there was significant overlap of the orbital cloud present in both the Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) of the molecule between the C atom of the triaza moiety belonging to the TBD catalyst and the O atom of the nitro group of the substrate. The Mayer bond order was of the C-O interaction was determined to be 0.138.

Full grid-search semiempirical calculations (AM1 and AM1/COSMO) on zwitterionic acetylcarnitine and carnitine, cationic acetylcholine and choline, and 3-acetoxypropanoate and 3-hydroxypropanoate in the gas phase and solution were performed. The calculated ΔH_hydr for hydrolyses of acetylcarnitine to carnitine and of acetylcholine to choline show reasonable agreement with the experimental values in unbuffered solution (acetylcarnitine: -4.63 kcal/mol calc. vs. -7.43 kcal/mol exp.; acetylcholine: -3.20 kcal/mol calc. vs. -3.06 kcal/mol exp.) The results suggest that a change in the conformational populations of acetylcarnitine-carnitine upon hydrolysis maintains a nearly constant polarity, which keeps the work of desolvation of the products to a minimum. Acetylcholine-choline and acetoxypropanoate-hydroxypropanoate present a much higher work of desolvation, therefore yielding a lower free enthalpy of hydrolysis. Ab initio calculations at the RHF/6-31G* level for the carnitines and the cholines, and RHF/6-31+G for the propanoates, were done to calibrate the quality of the AM1 results for both the gas phase and in solution. The calculations in the gas phase involved full optimization of the AM1-optimized structures at the RHF/6-31G* level and RHF/6-31+G level, and single points at the MP2//RHF/6-31G* and MP2//RHF/6-31+G level to estimate correlation effects. The ab initio calculations in solution were single points on the AM1-optimized geometries and used the Tomasi solvent model. The ab initio results confirmed the qualitative reliability of the semiempirical results. The conformational behavior of several 4,4-dimethylmorpholinium rings and 4,4-dimethyl-2-oxo-1,3,6-dioxazaphosphacinium rings was examined by molecular mechanics (AMBER* and AMBER*-GB/SA). The contrast between the behavior of these heterocycles and that of the parent saturated hydrocarbon systems formed a picture of the conformational behavior of these six- and eight-membered heterocycles. Influences of factors such as shortened bond lengths, varied bond angles, presence or absence of lone pairs and substituents, and dipolar alignment are described. Morpholinium rings show increased stabilization of the twist-boat with 1,1,3,3-di<i>gem</i> substitution, as compared to the parent cyclohexane systems. In the gas phase, the lowest chair/twist-boat energy gap is found in 2-(hydroxymethyl)-2,4,4-trimethylmorpholinium at 1.14 kcal/mol. The gap in the congruent hydrocarbon system is 5.23 kcal/mol. Differential solvation destabilizes the lowest energy twist-boat found in the gas phase, increasing the energy gap to 2.62 kcal/mol. The lowest chair/twist-boat energy gap in GB/SA water amounts to 1.45 kcal/mol, stabilized by solvation from an initial 2.13 kcal/mol in the gas phase. In the dioxazaphosphacinium rings, the preferred conformation in the gas phase is the boat-chair (BC) and the populations are conformationally heterogeneous. As substituents approach a 1,1,3,3-di<i>gem</i> pattern, the twist-chair (TC) and twist-boat (TB) conformers are stabilized. Solvation favors boat-boat (BB) conformers, with the substituents exerting influence on the conformational preference only to stabilize the TB in two instances (<i>cis</i>-substituted ring and disubstituted ring). Solvation reduces the heterogeneity of the conformational populations. Modeling of phosphonate moieties required development of molecular mechanics parameters for dimethyl methylphosphonate. Dimethyl methylphosphonate conformations were calculated at the RHF/6-31+G* level. Charges were calculated by the CHelpG scheme. The results were used to generate AMBER* parameters for modeling of alkylphosphonates in the gas phase and in solution. Comparison of the results of our AMBER* parameters against three other common force fields (MM2*, MMX and UFF) showed that AMBER* reproduced better the ab initio results when comparing absolute deviations in bond lengths, bond angles and torsion angles. The modified AMBER* reproduced better than the other three force fields several X-ray geometries of alkylphosphonates. / Ph. D.

Neste trabalho foram realizados estudos conformacionais de algumas lactonas sesquiterpenicas e cálculos teóricos de deslocamento químico. O estudo conformacional é dividido em tres etapas distintas. A primeira etapa se dá pela busca conformacional em mecânica molecular, onde foram encontradas as possíveis conformações assumidas pelo sistema em estudo. Na segunda etapa, as conformações encontradas foram otimizadas em mecânica quântica. O último passo neste estudo foi o cálculode deslocamento químico e a posterior correlação com os dados experimentais. / This work is aimed on the theoretical calculation of chemical shifts of sesquiterpene lactones, based on the conformational preferences of the compounds. This conformational study is set up in three stages. The first one is a conformational search using molecular mechanics, to assess the relevant conformations of the system under study. In the second stage, the conformations are optimized by quantum mechanics, for the refinement of both the structural assignment and energy calculation of the most stable conformers found in the previous step. The last step is the theoretical calculation of chemical shifts. Finally the weighted average of calculated values is compared to experimental data.