Aplicació de metodologies quimiomètriques a l'estudi de l'efecte del solvent sobre els aspectes termodinàmics i estructurals dels equilibris àcid-base dels polinucleòtids

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(1)Aplicació de metodologies quimiomètriques a l'estudi de l'efecte del solvent sobre els aspectes termodinàmics i estructurals dels equilibris àcid-base dels polinucleòtids Anna de Juan Capdevila. Aquesta tesi doctoral està subjecta a la llicència ReconeixementSenseObraDerivada 4.0. Espanya de Creative Commons.. NoComercial. –. Esta tesis doctoral está sujeta a la licencia Reconocimiento - NoComercial – SinObraDerivada 4.0. España de Creative Commons. This doctoral thesis is licensed under the Creative Commons Attribution-NonCommercialNoDerivs 4.0. Spain License..

(2) em o. 1. DEPARTAMENT DE. PROGRAMA. o. m. 0. o. QuiMICA ANALInCA DE LA UNIVERSITAT DE BARCELONA. QuiMICA ANALIncA DEL MEDI AMBIENT I DE LA POL·LUCIO. (BIENNI 1988-1990). DE DOCTORAT:. APLICACIO DE L'EFECTE. o. m. METODOLOGIES. QUIMIOMETRIQUES A L'ESTUDI DE. DEL SOLVENT SOBRE ELS ASPECTES. ESTRUCTURALS DELS EQUILIBRIS. Memoria. ACID-BASE. TERMODINAMICS. DELS. POLINUCLEOTIDS. presentada per Anna de Juan i Capdevila per optar al Ciencies Quimiques.. Directors: Enric Casassas i Sima i Gemma Fonrodona. I. grau de Doctor. en. Baldajos.. Barcelona, julio1 de 1997.. "alliilillii�TliIMr 0700452390.

(3) Enric Casassas i. Sima, catedratic emerit del Departament de Quimica Analitica. de la Universitat de del mateix. Barcelona, i Gemma Fonrodona Baldajos, professora titular. departament,. CERTIFIQUEN:. que la present. quimiometriques estructurals dels nostra. a. memoria, que duu per titol: "Aplicacio. de. metodologies. l'estudi de l'efecte del solvent sobre els aspectes termodinamics i. equilibris. acid-base dels. direccio per Anna de Juan i. polinucleotids", ha estat realitzada sota la. Capdevila al Departament de Quimica Analitica de. Universitat de Barcelona i que tots els resultats presentats son fruit de les. experiencies. realitzades per I' esmentada doctoranda.. Barcelona, juliol de 1997.. Enric Casassas i Simo. Gemma Fonrodona. la. Baldajos.

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(6) INDEX. INDEX. OBJECTIVES. STRUCTURE OF THE WORKS PRESENTED. I. GENERAL INTRODUCTION. CHAPTER 1. SOLVENTS AND SOLUTE/SOLVENT IN"TERACTIONS. .1-1. 1.1 Historical evolution of solvent to the. properties. 1.2. The. description:. from the bulk. microscopic parameters. ET(30) polarity. scale:. a. .I-I. uniparametric microscopic. approach. .. .1-7. 1.3. The solvatochromic .. comparison. a. multiparametric. .. microscopIC approach. 1.4. Solute behaviour Free. method:. vs.. .1-10. solvent effect: the establishment of Linear. Energy Relationships (LFER). .1-18.

(7) 1.4.1.. Hard-modelling methods. .I-22. 1.4.2.. Soft-modelling methods. .I-24. CHAPTER 2. SOLVENT MIXTURES. 2.1.. Looking. for the. perfect. .I-35. solvent: the alternative of solvent. mixtures. .I -35. 2.2. The water-dioxane. 2.3. Acid-base. .I-40. example. equilibria. in water/dioxane mixtures. .I-42. 2.3.1. Potentiometric studies. .I-43. 2.3.2. Data treatment. .I-45. CHAPTER 3. POL YNUCLEOTIDES IN WATERIDIOXANE MIXTURES. .I-48. 3.1. Structure of the. polynucleotides. and. particularities. of their. acid-base eq uilibria. 3.2. The environments. hydroorganic. .I -48. media used. as. emulators. of biological. •........................................................................................................... 3.3. Presentation of the. homopolynucleotides studied. •...................... .I-56. .I-59.

(8) 3.4.. Study. of the monomeric units of the. polynucleotides:. the model. of cyclic nucleotides. 3.5.. .I-60. Study of the homopolynucleotide. 3.5.1. Potentiometric. 3.5.2.. .I-62. monitoring. .I-64. Spectrometric monitoring. .I -65. 3.5.2.1. UV-visible spectrometry. .I-69. 3.5.2.2. Circular dichroism spectrometry. .I-70. (CD). 3.5.3. Data treatment. 3.5.3.1.. .I-72. data set. .I 76. 3.5.3.1.1.. Principal Component Analysis (PCA). .I-76. 3.5.3.1.2.. Evolving Factor Analysis (EFA). .I-77. Exploratory analysis. 3.5.3.1.3. Fixed-size. of a. spectrometric. Moving Window-Evolving Factor .I-81. Analysis (FSMW-EFA). 3.5.3.2. Resolution ofa. 3.5.3.2.1.. -. spectrometric. data set... Alternating Least Squares method (ALS). .I-83. .I-87.

(9) II. RESULTS.. CHAPTER 4. ON THE MICROSCOPIC DESCRIPTION OF SOLVENT SPACE. I. Solvent classification based. on. solvatochromic parameters. A. comparison with the Snyder .11-1. approach. CHAPTER 5. GOING FROM PURE SOLVENTS TO SOLVENT MIXTURES: THE WATER-DIOXANE EXAMPLE.. 5.1.. Microscopic. acid-base. characterization of the mixture and determination of. equilibria.. IT. Correlation of acid-base. properties. of solutes with the. polarity parameters and. other. solvatochromic parameters of dioxane-water mixtures. IT-12. >+. ITI. Determinaci6n del. Er(30). para mezclas. parametro de polaridad-polarizabilidad. 5.2.. Y correlaci6n de este. dioxano-agua. IV. Solvatochromic parameters for constants. Part I.. 1t. IT-21. binary mixtures. and. a. correlation with. equilibrium. Dioxane-water mixtures. Modelling. con. 11-26. of solvent-dependent processes in water-dioxane mixtures:. proposals for the establishment of Linear Free Energy Relationships. (LFER).. V. Assessment of solvent parameters and their correlation with. dioxane-water mixtures. using factor analysis. protonation constants in 11-42.

(10) VI. Factor. Analysis applied to the study. electrolyte nature. on. the. of the effect of solvent. composition and. of the inert. protonation constants in dioxane-water mixtures. CHAPTER 6. THE ACID-BASE. II-52. EQUILIBRIA OF. POL YNUCLEOTIDES IN WATER-DIOXANE MIXTURES.. 6.1. The. use. of curve resolution. techniques. to. interpret the multivariate. monitoring of biochemical processes: improvement and understanding the chemometric. procedures.. VIT. Assessment of new constraints. applied to the Alternating Least Squares (ALS). method. VIII.. .I1-63. Comparison between the Trilinear Decomposition (TLD). Squares (ALS) methods. 6.2.. of. and the. Alternating Least. for the resolution of three-way data sets. Application of curve. dependent transitions. resolution. of some. techniques. to the. II-75. study of pH. homopolynucleotides in water-dioxane. mixtures.. IX.. Application of a self-modeling. curve. resolution. approach to the study. on. the acid-base and. copper(II)-complexing behaviour ofpolyuridylic. X.. Three-way. resolution. curve. applied to the study of solvent. and conformational transitions related to the. XI. A. acid. on. the. protonation ofpolycytidylic. soft-modeling approach to interpret thermodynamic and. polynucleotides. effect. of solvent effects II-95. thermodynamic. acid. II-114. conformational transitions of .II-124.

(11) III. GENERAL DISCUSSION AND CONCLUSIONS.. CHAPTER 7. GENERAL DISCUSSION. CHAPTER 8. CONCLUSIONS. IV. REFERENCES. v. SUMMARY IN CATALAN.. .III-I. III-37.

(12) OBJECTIVES. The main. goal. thermodynamical. of this. project. is the. qualitative. and. of all the. quantitative description. and conformational transitions related to the acid-base behaviour of. several. polynuc1eotides in biological. special. environments has been carried out. aqueous nature of the. environments of low. polarity.. The emulation of these. by using water-dioxane mixtures. media and present the desired low. biological. that. polarity. the. keep. due to the. features of their cosolvent.. Owing. to. polynuc1eotides. the. complexity. associated with the macromolecular nature of the. and with the mixed character of the solvent used,. research must be carried out before. facing specifically. polynucleotide behaviour in water-dioxane mixtures.. some. fundamental. the research about the acid-base. These. previous. studies. include,. on one. hand, the detailed characterization of the water-dioxane mixtures and the interpretation of their effect. on. the acid-base behaviour of single solutes and,. the monomeric units of the. In all the work constant concern.. Solvation. performed,. the careful treatment of the. attention has been focused. Special. monitoring. effect, and. on. the. interpretation. of the macromolecular. been tackled. by using. equilibria. different kinds of. whereas the latter has been solved with the do not need the. species in. postulation. solution.. the other hand, the. study. of. polynuc1eotides in these mixtures.. Energy Relationships (LSER), behaviour. to the solvent. on. of. on. experimental. data has been. a. the establishment of Linear. models that relate the solute behaviour. of the multivariate data. polynucleotides.. hard-modelling application. of any chemical model to. and. coming. The former. from the. problem. has. soft-modelling methods,. of curve resolution methods, which. interpret. the variation of the different.

(13) STRUCTURE OF THE WORK PRESENTED. The series of articles included in this. the. study. which. of the acid-base behaviour of. begins with. project shows. in low. polynucleotides. the selection and assessment of the solvent. later characterization of the water-dioxane mixtures. microscopic characterization of their effect. on. bulk. monitoring. and the. I presents. an. the transition from the. solvent). to. the. solvent features in the. proposed by. solvents and with the. simple. solutes. interpretation. Kamlet et. according. to. are. used to structure the. quantify. the. of the acid-base behaviour of the. of the. mixtures formed. by changing. microscopic descriptors and. are. filled. covers a. space in solvent. by. members.. the infinite number of. wide. zone. of the solvent. project. Articles II,. proportion. polarity. scheme of Snyder.. microscopic properties. the. the. microscopic features of their. compared with the classical. determination of the. to characterize the. global solvent. space and has been selected for the later studies in this. experimental. The. description,. to characterize the. hydrogen-bonding. solvent mixtures. The water-dioxane system. hydroorganic. (articles II-VI) and finishes. macroscopic properties (suitable. similarity. the. interpretation. overview of the evolution in the solvent. al.. to the. used in the. (articles VII-XI).. The gaps among the groups of pure solvents. include the. descriptors. (article I), follows with. cybotactic region around the solutes).. This solvent classification is later. possible. polarity environments,. microscopic parameters (more appropriate. solute/solvent interactions groups built. hydroorganic. in these solvent mixtures. Thus, article. enhancing. of these. the acid-base behaviour of. with the multivariate. polynucleotides. the whole process followed in. III and IV. related to several. of dioxane from 0 to 100 %.

(14) (v/v). and the determination of. the mixtures. between. to. explain. alternatives to. fit the. are. data to. experimental. abstract model. into. (FA). of Factor. use. composition. and. presented and interpreted.. more. accurate behaviour models. Two. study.. the first involves. use. of. an. Analysis (FA). initial chemical. chemically meaningful. a. and solvent. a. possible. robust strategy. postulated chemical model (hard-modelling approach). a. which do not need the. between different sets of. solute property under. the. on. solutes dissolved in. simple. are. descriptors. proposed to build these LSER models:. and the latter combines the. (TF A),. microscopic parameters. devoted to the establishment of. the solvent effect are. constants of. Simple correlations. constants and solvent. protonation. Articles V and VI. protonation. characterized.. previously. microscopic parameters, between. some. and. Factor. Target. and transform. expression. LSER. Analysis an. (TFA) (soft-modelling. approach).. Once the water-dioxane system has been characterized and processes have been. analyzed. acid-base behaviour of. in it, the. study. polynuc1eotides,. can. output coming from these experiments is been. previously. focused. on. the. simple acid-base. some. of macromolecular processes, such. be carried out.. not a trivial. improvement. Handling. task; therefore,. of the. the. the. experimental. some. used. currently. as. research has. resolution. curve. method, the Alternating Least Squares method (ALS), through the proposal and assessment of. VII).. The. new. constraints to be used in the iterative resolution. performance. Decomposition (TLD) (article VIII).. ,. of this. another. method. curve. Simulated data with. a. has. been. large variety. used in both chemometric studies. After. with. compared. resolution method with. a. procedure (article. different. of. thermodynamical acid. polyuridylic. macromolecular. having confirmed. equilibria,. the. articles. IX-XI. acid. (polyC). and. studies carried out in aqueous solution. Articles IX and X of the. respectively,. compilation. pH-dependent. transitions of the. and of their related. cyclic. are. polyU-H. in. from the. detail. equilibria acid. coming. specifically and the. improved. coming. explain. polyadenylic. water-dioxane mixtures and compares these results with others. description. of the. suitability. and conformational transitions related to the acid-base. (polyU), polycitydylic. background. of features and real data have been. ALS method to handle data with the features of the multivariate output. monitoring. Trilinear. the. the. of the. (polyA). from. previous. oriented to the. polyC-H systems,. monomeric nuc1eotides. Article XI shows. of the results shown in articles IX and X and makes. in. an. a. intercomparison.

(15) between the chemical conclusions related to these two H system. This last article stresses. experimental. multivariate. biomacromolecular of information that. as. monitoring. equilibria through can. well the. and the. curve. polynucleotides. big potential resolution. be obtained when this. for the. polyA use. of. study. of. of the combined. techniques. systematic exposition. and to the. of all the different kinds. approach is followed..

(16) ARTICLES PRESENTED. I. Solvent classification based. solvatochromic parameters. A. on. comparison. with the. Snyder approach. A. de Juan, G. Fonrodona and E. Casassas. Trends in. 16. Analytical Chemistry,. II. Correlation of acid-base. properties. (1997). 52-62.. of solutes with the. polarity parameters. and other. solvatochromic parameters of dioxane-water mixtures. E. Casassas, G. Fonrodona and A. de Juan.. Inorganica. Chimica Acta, 187. III. Determinacion del con. (1991). de. parametro. 187-195.. polaridad-polarizabilidad 1t.. Y correlacion de este. ET(30) para mezclas dioxano-agua.. E. Casassas, G. F onrodona and A. de Juan. Anales de. Quimica,. 87. (1991). 611-615.. IV.Solvatochromic parameters for. binary. mixtures and. a. correlation with. equilibrium. constants. Part I. Dioxane-water mixtures.. E.. Casassas, G. Fonrodona and A. de Juan.. Journal. of Solution Chemistry,. 21. (1992). 147-162.. V. Assessment of solvent parameters and their correlation with. dioxane-water mixtures. protonation. constants in. using factor analysis.. E. Casassas, G. Fonrodona, A. de Juan and R. Tauler.. Chemometrics and Intelligent Laboratory. VI. Factor. inert E.. Analysis applied. to the. Systems,. 12. (1991). study of the effect of solvent composition and of the. electrolyte nature on the protonation constants. in dioxane-water mixtures.. Casassas, N. Dominguez, G. Fonrodona and A. de Juan.. Analytica. Chimica Acta, 283. 29-38.. (1993). 548-558..

(17) VII. Assessment of. constraints. new. applied. to the. Alternating. Least. Squares (ALS). method. A. de Juan, Y. Vander. Analytica. Chimica Acta,. VIII.Comparison. (1997) (in press).. between the Trilinear. Squares (ALS) methods A. de. R. Tauler and D.L. Massart.. Heyden,. Juan, S.C. Rutan,. Decomposition (TLD). of. a. Alternating. Least. for the resolution of three-way data sets. R. Tauler and D.L. Massart.. Submitted to Chemometrics and Intelligent Laboratory. IX.Application. and the. self-modeling. curve. resolution. Systems.. approach. to the. study. of solvent. effects. on. A. de. Juan, G. Fonrodona, R. Gargallo, A. Izquierdo-Ridorsa, R. Tauler and E.. the acid-base and. copper(II)-complexing behaviour of polyuridylic. acid.. Casassas. Journal. X.. ofInorganic Biochemistry,. Three-way. curve. thermodynamic. resolution. and. 63. applied. conformational. (1996). to. 155-173.. the. transitions. study of related. solvent to. the. effect. on. protonation. the. of. polycytidylic acid. A. de. Juan, A. Izquierdo-Ridorsa, R. Gargallo, R. Tauler, G. Fonrodona and. E.. Casassas.. Analytical Biochemistry (1997) (in press).. XI.A. soft-modeling approach. to. interpret thermodynamic. and conformational transitions. of polynucleotides. A. de Juan, A.. Izquierdo-Ridorsa,. R.. Tauler, G. Fonrodona and E.. Biophysical Journal (1997) (accepted for publication).. Casassas..

(18) I. GENERAL INTRODUCTION..

(19) 1.1. A historical review of the. description. .... CHAPTER I.. SOLVENTS AND SOLUTE/SOLVENT INTERACTIONS.. 1.1 A historical review of the to. bulk. properties. microscopic parameters. Progress. the. description of solvents: from. in all fields of chemistry has been. understanding. was. processes. seen. as. much. was. active element. an. more. always. in. been. than "container of solutes". For them, the for the evolution of the chemical. responsible. of the alchemists. concerns. solvent, the so-called alkahest. For this. utopian. substance.. discovery of new solvents. Though. and processes. appeared during this period; however,. this. the first to. remained in solution,. solution after. question. though. applying. in. an. numerous. increase the. attempts. a. universal. were. made at. was never. attained,. general understanding. elementary rules,. such. as. the. of the. "like solves like". the concept of solution remained vague and the loss. this. was. theory.. widely accepted. He. "aqueous" form,. the suitable. the identification of. specific objective. helped to. of the nature of a substance with dissolution was. was. centuries,. some. role of solvents and solutes in solution. Certain. Helmont. developments. occurring in solution (Boerhaave,1733), (Reichardt,1988).. One of the main. revealing. the. of solvents and solutions. From earliest times, there have. researchers for whom the solvent solvent. closely connected to. procedure.. 1-1. argued. In the 17th century, Van. that the substance. as. such. and believed it could be recovered from. This alternative. gradually acquired general.

(20) 1.1. A historical review of the. description. .... acceptance by the end of the 19th century, supported by Van't Hoffs theory of osmotic. theory of electrolyte dissociation.. pressure and by Arrhenius's. The first solvent effects. reported. Berthelot and Pean de Saint Gilles. chemical reactions in 1862. concerning. haloalkanes became. a. such. as. revealed. the. of tertiary amines with. alkylation. separated from the. medium in which it is. The influence of solvents in chemical. Claisen. (Wis1icenus,1896) in1896. on. of reference and many fundamental statements in this. (Menshutkin,1890).. separately by. Within the kinetic field, Menshutkin' s. the solvent effect. "a chemical reaction cannot be. remain valid. the first to notice the solvent effect in the rate of. (Berthelot,1862).. contribution in 1890. point. were. also date from the end of the 19th century. Thus,. from studies conducted. performed". equilibria. was. (Knorr, 1896) and Wislicenus. Knorr. (Claisen, 1896),. study,. the keto-enol tautomerism of 1,3-. on. dicarbony1 compounds.. The. description. key. to. of the solvent. and extent of the was. considered. refractive index be the best. highly. explaining. the solvent effect in all chemical. itself, thus leading. to. nonstructured dielectric continuum and. (n) and. the relative. properties by. suitable for. solutes. For. permittivity. or. characterizing. the bulk. long time,. a. dielectric constant. solvent, do. (6). solvent effects. Indeed, the solvent around solutes. uniform medium, but molecules that interact. The. as. structured dis continuum. complete description the. of. a. measurement of. longer. consisting. the. supposed. properties. to. while. specific caused. be considered. as a. of individual solvent. solvent must then include both. former. mainly. related. (e.g., electrostatic contributions) and the. solute/solvent. as. specifically with each other and with solutes.. microscopic parameters, interactions. a. were. not take into account the. can no. good. the solvent. macroscopic properties,. solute/solvent interactions and often fail to correlate variations in solute. by. a. constants such. physical. which it could be described. These. lies in. of both the nature. simpler interpretation. a. possible interactions performed on the a. phenomena. interactions. (e.g.,. is. an. 1-2. easy. nonspecific. latter to the. hydrogen-bonding).. macroscopic properties. to. macroscopic. task, there is. solvent/solvent. quantitation. Whereas no. the. and. of. specific. experimental. direct instrumental.

(21) 1.1. A historical review of the. the. to. access. obtained. using. environments. Therefore,. microscopic alternative. .... must be. microscopic descriptors. to those. experimental strategies. description. in the determination of. applied. macroscopic physical properties.. the. Given. close. measurements of solute. surrounding. possibility. by measuring. the effect that the former has common. microscopic parameters (Reichardt, 1988).. behaves. probe. as a. in the solvation shell. variations in its. through. and. solvent,. experimental. indirect information about the solvent. obtaining. processes is the. strongly solvent-dependent solvent. of. solutes. information about the solute itself and about the. properties provide. solvent. The. around the solutes. between. relationship. basis for many. scales of. empirical. In these processes, the solute involved in the. reflecting changes. absorption spectra. certain well-known and. on. or. in. thermodynamic. some. solvent. surrounding. kinetic. or. parameters.. The first. empirical. scale. was. defmed. by Winstein. in 1948. (Winstein,1948).. He. proposed a Y parameter to represent the "solvent ionizing power", which was built from the measure. of the kinetic constant related to the SN 1. Additional or. have. also. approach proposed by been. employed. (Drago,1965), (Maria, 1985). proposed. as a measure. negative value. dichloroethane. of the solvent Lewis. of the molar. as. in the. the X scale. enthalpy. establishment. for the adduct. donor solvents measured in. (Gielen, 1963). (Swain, 1955). Equilibrium of a. empirical parameters well known. basicity (Gutmann,1966);. DN is defined. formation between. highly. example as. the. antimony. diluted solutions of 1,2-. inert solvent.. properties, empirical scales using spectroscopic. simplicity. in the. absorption spectra. absorption. are. Swain et al.. Despite the proven value of empirical parameters. of the overall. 2-chloro-2-methylpropane.. Gutmann's donor number, DN, is. pentachloride and electron-pair. solutes. of. examples of scales with kinetic reference processes. the four parameter. processes. solvolysis. bands due to the. data. based. are more. on. kinetic. thermodynamic. generally employed. recording of the related experimental. show. or. measurement.. because. Indeed,. changes in the position, intensity and shape of their. solvent-dependent 1-3. alteration of the energy difference between.

(22) 1.1. A historical review of the. the. ground. description. .... and the excited states of their. potential usefulness of solvatochromic dyes properties (Brooker, 1951). on. In. chromophores. in. solvent. the. quantifying. Seven years later, Kosower set up the first. spectroscopic properties (Kosower, 1958a; 1958b; 1958c).. charge. 1951, Brooker suggested the. transfer transition of. His Z. empirical. polarity. iodide. l-ethyl-4-(methoxycarbonyl)pyridinium. microscopic. as. scale based. scale took the. spectroscopic. reference process.. The many solvatochromic scales which exist. spectroscopic. built from UV, visible. measurements and often take solvent-sensitive n�. transfer transitions. spectral changes solutes of. are. as. reference. due to solvent. empirical. an. spectroscopic effects,. processes.. Though. n*,. many. n�. n*. or. near-IR. or. charge. compounds exhibit. not all of them are suitable for use as reference. solvent scale. An ideal solvatochromic. probe. should fulfil the. following requirements: •. High sensitivity. to. dependent bathochromic corresponding to. the. in. changes or. the. surrounding. hypsochromic. shifts in the. position of the wavelength. absorption band maximum must be. always significantly larger. The solvent. medium.. as. large. as. possible. and. than the instrumental accuracy associated with the. wavelength location. •. Large. molar. absorptivities.. Solvatochromic indicators. solute/solvent interactions. Therefore, the molar must. be. large enough. are. of these substances. absorptivity. in all the solvents studied to allow. one. used to describe. to work with. diluted solutions, in which the existence of spectral shifts induced. interactions caused •. Absorption. by the aggregation of probe molecules. band out of the solvent. solvatochromic shifts is bands of the •. Solubility.. probe. more. and the solvent is absent. probe. different features in order to obtain •. Low not. reactivity.. be altered. by solute/solute. be discarded.. spectral region. The estimation of. accurate if the. The solvatochromic. can. overlap between. or as. small. as. must be soluble. the. the. absorption. possible. ,in solvents with. representative empirical. many. scales.. The chemical nature of the solvent-sensitive. chromophore. by any chemical reaction between the indicator and the. 1-4. highly. must. solvent..

(23) 1.1. A historical review of the. •. Stability.. The reference solute must be. crystalline substance with. a. defined chemical structure, stable in storage and in solution •. Availability.. The. probe. must be. description. perfectly. a. .. available or, at least,. commercially. .... easily. synthesized.. The evident. shortcoming of all. that the solvent behaviour around the. kind of solute. This bulk solvent. the solvatochromic scales is the inherent. probe molecule. describe the. probes. reference solute. on. empirical. the. sufficiently. small. If this is not the case, the. dispersion. solute/solvent interactions. among the results. are. microscopic environments. There scales: the the. are. will. solvent-dependent. and reference processes which process under. are. a. which the. of as. to the. empirical. forms of solute/solvent interactions in. a. global picture. of the solvent. Both. complementary information they provide,. solute/solvent interactions. on. the. one. a. and. scales. working. solute.. a. The former tries to include all. single parameter,. use. empirical. whereas the latter. hydrogen-bonding, polarizability, ) .... of all these. approaches. can. be. specific parameters. is. equally useful owing. to. global intensity. hand and to the nature of these interactions. 1-5. with. to the solute and the. possible. which is related to the. other.. sound. carelessly averaged. construction of solvatochromic. separate parameter and it is the combined. gives. valuable. more. whose. also reduce the differences between the. probe and around the. approaches. be. only. single probe-based scales, yield. use. associates each kind of solute/solvent interaction (i.e., with. coming. all the indicators considered is. uniparametric and the multiparametric approaches.. possible. that the. values. this average will. processes than. similar. as. study will. around the. two marked. of. use. additional recommendation, the. solvent-dependent. using averaged. provided by. clearly defined,. conclusions about the evolution of. probes. scales. microscopic parameter. Nevertheless,. if the. an. dangerous than assuming. in order to minimize the influence of the different nature of each. meaningful. parameter. As. that around any other. same as. environment around the solutes. Some. microscopic. authors recommend the establishment of from several. less. oversimplification is, however,. properties. is the. assumption. of the on. the.

(24) 1.1. A historical review of the. Most of the. polarity. description. uniparametric. .... solvatochromic scales. scales. In this context, the term which. capability,. depends. on. all. possible. polarity. probes used in these. solvatochromism, such. scales. are. merocyanines. as. Reichardt. (Dimroth,1963),. (Dahne,1975), the �. (Dong,1982).. or. From all the scales. probe,. RPM. scale of Dubois. in this. uniparametric approach reference. the. (i.e., protonation, oxidation, ). .... pyridinium N -phenolate. to the wide. correlation found between. multiparametric approaches. or. the. one. Dahne. of. and Winnik. the. large negative. solvatochromism of its. of solvents covered. uniparametric scales, are. selected. or. by. as. this scale and to the. good. the solvatochromic indicators used in. giving priority. to the. forming. a. specificity. and Fawcett. The most successful and. one. are. source. those. are. basicity. respectively (Taft,1976), (Kamlet,1976), (Kamlet,1977). Owing each of the parameters above caused. an. by. of solutes whose of solute/solvent. and Swain et al.. and. a,. f3. and. polarity-polarizability,. to the. great specificity of. probes. ability to describe variations of solvent. 1-6. is the. Taft and Abboud. The. the careful selection of the solvatochromic. used in their determination and to their proven. are. only kind of. separated in the solvatochromic parameters bond. a. of the exhibited. generally applied multiparametric approach. hydrogen bond acidity, hydrogen. for. proposed by Koppel. (Krigowski,1975). comparison method, proposed by Kamlet,. different solute/solvent interactions. probe. multiparametric approach. possible, by taking pairs only. of the. magnitude. reference solutes sensitive to. more. (Koppel,1971), Krigowski. 1t* related to the. Dong. and. due to the. examples of multiparametric approaches. so-called solvatochromic. uniparametric. has been chosen. difference in solvatochromic behaviour is due to. (Swain,1983).. are. family, ET(30). solute/solvent interaction or, when this is not. and Palm. which. to this. solvatochromic shift. The several parameters. interactions. Known. of. scale. scale of. Py. certain kind of solute/solvent interaction rather than to the. by taking. examples. dyes,. ET(30) parameter and many other empirical parameters.. In contrast to the. determined. betaine. Polaritatsmass). (Relative. belonging. variety. any. For this. ET(30) parameter proposed by Dimroth. (Dubois,1966). project. cause. usually substances with a large solvent-dependent. the aforementioned Z scale, the. are. solvent. as. for the overall solvation. accounts. able to interact in many diverse forms with the solutes. Some. approaches. defined. generally. solute/solvent interactions which do not. definite chemical alteration in the reference solute reason, the. are.

(25) 1.2. The. processes with linear models. dependent. interactions most. represented by. a.,. p. and. including weighted. selected for. Though the application of the most popular empirical decades, the microscopic solvent description is today. used. in this field include. a. clearer. scale. .... of the solute/solvent. n*, the solvatochromic comparison method is the. widely used multiparametric approach and has been. subjects. sums. Er(30) polarity. an. in this. use. scales dates back. active research. project.. a. number of. area.. Current. of the solvatochromic indicators. understanding. being. (Dealencastro, 1994), (Boggetti, 1994), (Ramirez,1995), the proposal of new potential. dyes with better solvatochromic properties solute. concrete. some. specifically. or. describe. gas. (Spange,1996). or. the. phase. the establishment of. of. adaptation. environments in. microscopic. (Schulte, 1995),. or. fluids. solid. (Koppel,1994),. of. so. empirical that. scales. they might. (O'Neill,1993), (Sun, 1995),. phase. (Park, 1994),. such. solutions,. microheterogeneous. new. existing parameters. supercritical. interpretation. (Reichardt, 1995a; 1995b),. (Scremin,1994),. processes. (Effenberger,1995), (Albert,1996), (Lu,1996), (Drago,1994), (Catahin,1995). oriented to the. as. micellar. (Li,1995), systems. (Drummond, 1986).. 1.2. The. ET(30) polarity scale:. The measure. ET(30) parameter. of solvent. establishing. this. was. a. uniparametric microscopic approach.. proposed by. The. polarity (Dimroth,1963).. empirical. scale is the. Dimroth and Reichardt in 1963. solvent-dependent. the molar transition energy. under. study measured. evaluated. at. by introducing. (in kcal/mol). 25° C and. the wavenumber of the. ET(30) (kcal/mol). =. and each. of the reference. at normal pressure. aforementioned transition in the following. a. process used in. n* electronic transition of the solvatochromic. n �. dye 2,6-diphenyl-4-(2,4,6-triphenyl-l-pyridinio )phenolate as. as. NA h. 1-7. c. Vmax. value is defmed. dissolved in the solvent. (Reichardt, 1988). Thus, ET(30). absorption. expression:. dye. ET(30). is. band maximum related to the.

(26) 1.2. The. Er(30) polarity scale. .... The dimensionless derivation of the. tetramethylsilane (TMS). taken. are. as. ET(30). scale is the. ETN scale,. where water and. polar and non-polar reference solvents,. extreme. respectively (Reichardt, 1983).. The. transition. unusually large. employed in the establishment of. from water to. ground. solvatochromic shift associated with the. diphenyl ether). comes. charge. ET(30) scale (LlA. =. 357. nm. when. going. from the great difference in solvation between the. and the excited state of the betaine. decrease associated with the. the. solvent-dependent. dye.. This difference stems from the. transfer from the. phenolate. group to the. polarity. pyridinium. part of the molecule during the transition (see Figure 1.2.1.).. hv -. Figure. 1.2.1. Chemical forms of the. ground. and excited states of Reichardt's betaine. The chemical structure of Reichardt's betaine. sensitivity of this. responsible for. of the molecule allows the detection of. dipole/induced dipole interactions,. the solvent. the great. the. large polarizable. dipole/dipole. hydrogen-bonding acidity. hydrogen-bonding basicity. pyridinium moiety. of the. surrounding. a. rather basic. solvent. In contrast,. cannot be detected because the. is delocalized and. positive charge. sterically shielded, thereby preventing. 1-8. and. n-electron system, which includes. electrons, registers the dispersion interactions, and the phenolate group is. center, sensitive to the. the. is. molecule to many different kinds of solute/solvent interactions. Thus, the. large permanent dipole. 42. dye. dye.. of. the.

(27) 1.2. The. ET(30) polarity. scale. .... establishment of interactions between the basic center of the solvent and the acidic center of the. probe (Reichardt,1994).. Another. reference. dye. outstanding quality. with solvents with. of this parameter. are. of the. reported for more expand. considerable efforts to. obtaining. These substances. ET(30) reference dye and. are. compatibility. the. than 350 pure solvents and many. ET(30) scale, Reichardt. new. measurement of the. probe molecule. has been. substituted betaines that. keep. and. slightly. deal with low. acidic solvents. can. be. solvents; thus,. a. perfectly. betaine with. new. groups, which decrease the basic power of the. a. betaine with. CFJ. be it with the. very acidic solvents and in the gas. phenolate. group. �t-i c:. by modifying the basic ET(30) dye.. original ET(30) dye. phase.. soluble,. �o. Despite the wide applicability of Reichardt's polarity scale, experimentally determined,. not. groups. electron-withdrawing. FJC. 1.2.2. Some solvatochromic indicators obtained. dyes adapt. phenolate group (Reichardt, 1993).. F,c. Figure. with the. tert-butyl. polar solvents, in which the ET(30) dye is. analyzed by using. is not. the basic skeleton of the. whose solvatochromic behaviour correlates. to a concrete group of. designed to. solvent. have devoted. ET(30) parameter. behaviour of their parent molecule. The substituents introduced in these the. measures. common. and col.. of the. indicators suitable for the determination of this. parameter in solvents where the direct. possible.. scale is the great. wide range of features and behaviour. Direct. a. mixtures. In order to. ET(30). or. no. ET(30). values. can. be. with their derivatives, in. In the first case, the oxygen atom of the. protonates and the charge transfer solvatochromic absorption band. 1-9.

(28) comparison method. 1.3. The solvatochromic. disappears and,. in the second case, the betaine. measurement in gas. ET(30). .... phase. The ET(30). where. polarity scale,. (Reichardt,1983). The. gas. values. are. not volatile. enough. for very acidic solvents have. reported. measurements for acidic solvents. experimental. to allow the. expression correlating this empirical. then to be calculated from the mathematical. the Z. dyes. scale with. are. available. phase ET(30) value, equal to 27.1 according to a recent review of. Reichardt, is the average of the concordant results evaluated from theoretical and empirical used. relationships. in. independent approaches (Richert,1993), (Jano,1992),. several. (Reichardt, 1994).. 1.3.. The. solvatochromic. comparison. method:. multiparametric. a. microscopic approach. The solvatochromic. quantify, chemical. correlate and. comparison. solute/solvent interaction. Thus, the solvent. a. as. an. approach. solvent effects. Abboud and Taft proposed. solvent parameters, each of them. (Taft,1976), �. born. was. interpret multiple interacting. properties (Kamlet, 1983). Kamlet,. microscopic. solvent. method. specially designed. on. a. to. unravel,. many kinds of. series of empirical. to account for a. specific. represents the solvent hydrogen-bond donor acidity and n* the. hydrogen-bond acceptor basicity (Kamlet,1976). polarity/polarizability (Kamlet,1977).. These parameters. are. usually determined. from. spectroscopic measurements, hence the generalized name of solvatochromic parameters.. The solvatochromic parameters in. explaining. were. designed. the solvent effect in the solute. Energy Relationships (LSER). The. to be included in linear models used. properties,. the so-called Linear Solvation. most extended form of LSER. proposed by Kamlet. et al.. has the form:. XYZ. where XYZ is the. property in. a. =. (XYZ)o +. an +. solvent-dependent. hypothetical. b�. +. s(n*. +. d8). +. h8H2 + e�. solute property under. study, XYZo is. the value of this. inert solvent unable to interact with the solute, a,. 1-10. �. and n*. are.

(29) 1.3. The solvatochromic. the aforementioned solvatochromic parameters, 8 is o for nonchlorinated. aliphatic solvents,. polarizability correction term equal. a. 0.5 for chlorinated. 2. aromatic solvents, � is the square of the Hildebrand the solvent contribution to create whose value. depends. The coefficients a,. on. depending on the. and solutes used in. coordinate. a. and accounts for. covalency term,. indicate the weight of their related solvent parameters. e. variation of the XYZ solute property. This extended terms. is. S. nature. doing. of the. f3. expression. solvent-dependent process. Actually,. so.. solvatochromic parameters a,. a more. can. be reduced. studied and. expression which. basic. and 1t* is often taken. the. as. one or. two of them have. proved useful in. the accurate. by. includes. several. only. starting point. description. the. on. the solvents. on. establishment of LSERs. Linear models constructed from all three parameters. only. to. solvents and 1 for. aliphatic. solubility parameter. and. cavity. .... the nature of the basic functional groups present in the solvent.. s, h and. b,. solute. a. comparison method. the. in the. by. or even. of a wide. variety. of. solvent-dependent processes (Kamlet,1985).. The three solvatochromic a,. philosophy. Thus, the. linear model. Vmax. where the. depends with. solvent. and 1t* scales. underlying these. =. v, + aa +. bf3. +. built. are. on. of the terms in the. scales is:. S1t*. equation. above. Thus, the. a. and. f3. scales work. of reference solutes whose difference in solvatochromic shift correlates with the. hydrogen-bond acidity. scale is established. by using. a. correlated with the solvent. and solvent set of. hydrogen-bond basicity, respectively. solvatochromic indicators whose. polarity/polarizability.. All the. f3. shift detected is due. only to variations. and the 7t*. shift is. only. data used in the. ensure. that the. spectral. in the solute/solvent interactions and is not caused. thermosolvatochromic effects (Nicolet, 1986); the chemical. meaning and the. solvatochromic parameter determined from spectra recorded. seriously damaged owing to. spectral. spectral. and 1t* values must be recorded at 25°C to. determination of a,. would be. the basis of the LSER. spectral shift in the maximum of the absorption band of each reference probe. on one or more. pairs. f3. the variations in the. position. absorption band caused by modifications of this chemical variable. 1-11. at. by. accuracy of any. different temperatures and. shape of the probe.

(30) comparison method. 1.3. The solvatochromic. The. scale. n*. was. .... in. proposed. but. as a measure. establishment of pure. Apart from fulfilling,. as. Vo + aa +. to the more. +. bf3. sn* used in the. terms related to. much. f3. '*. 0). a. or. is shown to be. =. f3. paid =. to the. O. When. hydrogen-bond. selected must not present the solvent studied,. i.e., they. basic solutes. =. solvents. (i.e., big. (a. 0). (HBA-D,. reference. as. possible,. values).. out from the. (NHB). on. the. general. features listed in. reducing the LSER model. solvent. general. Vrnax. are. a '*. no. analyzed.. donor solvents. (HBD,. a '*. hydrogen-bonding capacity (b. =. '*. 0). In this case, not much. hydrogen-bonding. =. which. 0),. with the. and. probes. interactions with the solute. are. with. higher. a. complements. problem arises. use. 0. that of the. for the HBA solvents and. large enough. =. the reference solutes. have to be handled because of the. hydrogen-bonding abilities. more. 0, f3. 0). The best solution here is the combined. solvent molecules is. contributions. The. dealing with hydrogen-bond acceptor solvents (HBA,. must be non-acidic solutes. 0, f3. polarity. LSER model when solvents. to interact via. probe ability. sensitivities and weak IIBA. hydrogen bonds. only affected by. for the HBD solvents. The greatest. probes with s. of this. nature. Vo + sn*. this kind of interactions. develop. solvent, since. =. hydrogen-bonding drop. attention should be. and. specific. to the. only. specific expression:. spectral shift. not able to. the solutes due. general description of any solvent-dependent spectral shift. Vmax. where the. single. the solvatochromic indicators selected for its. section 1.1., the choice of these indicators is also focused =. scales of. the solvent overall. being. interactions. The. polarity/polarizability on. on. of solvent. measure. previous polarity. of the solvent effect. empirical parameter depends largely determination.. empirical. an. not understood here as. parameters, the concept of polarity is. ability,. as. In contrast to. polarity/polarizability (Kamlet,1977).. solvation. 1977. when. non. amphiprotic. difficulty. in. finding. solvatochromic shifts. ofNHB solutes with lower. sensitivities where the. hydrogen bonding. too weak to be noticed or where the autoassociation of. favourable than the. with the reference solute.. 1-12. disrupting. of this self-association to form.

(31) 1.3. The solvatochromic. To avoid the presence of the. specific effects of one indicator,. comparison method. the n* values. five. classified. probes. were. firstly proposed. substances present p. for. application. n*. �. in non-HBD solvents. to their. according. or n �. consistent with the solvent. clearly. such. causes,. cyclohexane. experimental. as. and. equal. to 1 for. and the terms Vo and. respected. Despite. s. are. in the determination of the n* parameter. All these. in HBD solvents. polarity. error. (Kamlet,1977) concerning. the. correlated with each other. are. and whose. well). spectral shifts. are. variation and cannot be attributed to other anomalies. n* values. spectral. or. as. dimethylsulfoxide. are. fixed. suitability of the. reference. as. calculated for each indicator. classification made in the. the. Forty. with the different kinds of solvent. compatibility. n* transitions whose Vmax. (and sometimes. often. are. determined from the average solvatochromic behaviour of several reference solutes.. .... indicators. points. 0 for. to. on. the scale. that these references. so. earliest. equal. work. proposed. of Kamlet. et. are. aI.. for the various kinds of. solvent, the results obtained from the several substances used in the determination of n* values must be. checked before. clearly unlike that. of the other substances. have shown that the n* values. empirical of. only. being averaged. prevent the appearance of. to. values which could arise from the inclusion of inadequate indicators. meaningless behaviour. carefully. scale. one. established. was. are more. indicator-dependent. (Brady,1982). indicator whenever. (Cheong,1988). Indeed, was. and the recent tendencies. From the. possible.. than. set of. primary. the. dimethyl-4-nitroaniline (proposed. as. an. use. alternative to the. can. be used instead. The. a. and. hydrogen bonding. 13. overlap. to. the. between. original probe N,N-diethyl-4solvent-dependent. band. (Laurence,1994).. scales used to. were. owing. of this substance, the N,N. nitroaniline due to its weaker vibrational structure, i.e., to its less. shape). use. probes proposed by. of its band shape from solvent-to-solvent. When the extreme. probe and the solvent absorption bands prevents the. when this. towards the. Kamlet et aI., 4-nitroanisole is considered the best reference substance. invariability. a. several studies. supposed are. showing. quantify the. solvent. established in 1976; the. acidity (Taft,1976). a. ability to. scale. whereas the. solvent. hydrogen-bond. solvent. hydrogen-bond acceptor basicity (Kamlet, 1976).. donor. 1-13. was. interact with the solute via intended to represent the. 13. scale accounted for the.

(32) 1.3. The solvatochromic. straightforward. shows Vmax. as. the. procedure. polarity indicators,. related. =. only a. .... of both. experimental determination. The. the. comparison method. to. there is. f3 parameters is. and. a. used to obtain 1t* values. In contrast to the. no. hydrogen-bonding. of. possibility. finding. any. interactions with the solvent, i.e.,. spectral shift that can be simply defined by LSERs models. v, + sa because all the solutes. also show. protocol. hydrogen-bonding. followed in. and. isolating. quantifying. interactions involves the selection of. basic. hydrogen-bonding. interactions. These. which is able to. develop hydrogen-bonding. both substances. can. determination of determine. such. spectral single =. as Vrnax. of. shift is. substance Vo +. sf3. or. capable of developing hydrogen bonding interactions. the contributions related to. a. be. homomorph,. f3 values,. or. such. not, such. as. of solutes whose. pairs. difference in terms of solvatochromic behaviour is due to their or. no. specificity. as. polar interactions.. The. acidic. whose. probe. not. pairs. varying ability. are. formed. interactions and another. as. 4-nitroanisole and. one. to establish. one. substance. unable to do so;. 4-nitrophenol. used in the. Reichardt's betaine and 4-nitroanisole used to. values. Whatever the nature of the two solutes involved, the. applied in the determination. by. only. pairs. of hydrogen-bonding parameters must fulfil the. of indicators. following. three. requirements: a) there. must be a linear. relationship. with. a. strong correlation between the. indicators when measured in solvents unable to modifications in the in the. spectral. polar. Vrnax of both. develop hydrogen-bonding interactions, i.e.,. solute/solvent interactions must. cause. the. same. kind of variation. shift of both substances,. b) experimental. measurements. in. performed. hydrogen-bonding. solvents must show. a. significant displacement from the aforementioned linear relationship, and c). the direction and. solvent. magnitude. of the. displacements. hydrogen-bond donor acidity (for the. a. scale),. should reflect when. one. a. reasonable order of. of the solutes in the. basic, and of solvent hydrogen-bond acceptor basicity (for the f3 scale), when. one. pair is of the. reference solutes is acidic.. Bearing. in mind these. conditions, the. a. scale is built. enhanced solvatochromic shift for Reichardt's betaine 1-14. (2). taking advantage. relative to 4-nitroanisole. of the. (1) in.

(33) 1.3. The solvatochromic. HBD solvents.. Thus, from the. in. performed. measurements. a. comparison method. series of NHB solvents. .... (in. kK), the following linear model is found:. v(2)max. Experimental v(2)max measured in HBD solvents. =. -1.873v(1)max +. values. clearly. probe. and the 4-nitroanisole. The solvatochromic. probe in HBD. Illlv(2-1). where. v(2)max(exp) is. the. solvents. =. and. which do not take. model when. place. displacement associated. can. be. they. are. between. between the solvent. with the. hypsochromic. quantified as:. -. betaine wavenumber in. experimental. relating v(2)max. of the solvent. previous. v(2)max( exp) v(2)max(calc). v(2)max(calc) is the betaine wavenumber linear model. deviate from the. owing to the presence of hydrogen bonding interactions. the acidic solvent and the basic betaine. shift of the betaine. 74.58. calculated for the. v(l)max in. hydrogen-bonding acidity. same. NHB solvents. The. scale is the methanol. Since the methanol solvatochromic. displacement, Illlv(2-1),. calculation of the. donor. hydrogen-bond. acidity. an. HBD solvent and. HBD solvent. single a.. has. fixed reference. value, a. by using. set. equal. the. point. to one.. value of 6.24 kK, the. for any other solvent will follow the. expression:. 0.1. where the. by using. SUbscript. the solute. Additional donor. yield. 0.2. are. Illlv(2-1)/6.24. I in the term 0.1 denotes that this solvent parameter has been evaluated. pair. examples. acidity. =. formed. of solute. Brooker's. values,. or. by probes. 1. (4-nitroanisole). pairs proposed. complex. dimethylaniline ]bis( cyano )iron(II) (5) (Burgess,1970). 1-15. (Reichardt's betaine).. to determine the solvent. merocyanine (3) (Brooker,1965) Burgess'. and 2. hydrogen-bond. and 4-nitroanisole. (1), which. bis[a.-(2-pyridylbenzylidene)-3,4and N ,N-diethyl-4-nitroaniline. (6),.

(34) 1.3. The solvatochromic. comparison method. .... used to obtain the 04 values. Chemical also been. applied to determine. to the a. Analogous. linear. relationship. follows the. spectral shifts. which differ from the. have. further aj values.. scale, the 13 scale is built using the enhanced solvatochromic. (1) relative. shift for 4-nitroaniline. properties. to. between the Vrnax. in HBA solvents. The. N,N-diethyl-4-nitroaniline (2). (in kK). of both indicators measured in NHB solvents. expression:. v(1)rnax. =. l.035v(2)rnax + 2.64. Bathochromic shifts associated with the 4-nitroaniline when dissolved in HBA solvents. cause. clear deviations in the. model. These solvatochromic. experimental v( l)rnax. displacements. values from the. stem from the presence. interactions between the basic groups of the solvent and the group in the. 4-nitroaniline, interactions which. nitroaniline since the are. hydrogen atoms. replaced by ethyl. cannot take. linked to the amino. The solvatochromic. groups.. hydrogen. place. where. v( 1 )rnax(exp). v(1 )max( calc) is. using. is the. point. of. N,N-diethyl-4-. displacement. associated with the. as:. v(l)rnax(calc) v(l)rnax(exp) -. experimental. 4-nitroaniline wavenumber in. relating v(2)rnax the. atoms of the amino. nitrogen in its homomorph partner. the 4-nitroaniline wavenumber calculated for the. the linear model. reference. =. linear. hydrogen bonding. with the. bathochromic shift of the 4-nitroaniline in HBA solvents is calculated. -��v(I-2). of. previous. solvent. hexamethylphosphoramide 13 value,. set. and. v(l)max in. an. same. HBD solvent. NHB solvents. The. hydrogen-bonding. basicity. to one. Since. -��v(l-2). equal. HBA solvent and. single. scale =. fixed the. 2.8 kK for this. solvent, the hydrogen-bond donor basicity for any other solvent can be calculated. 1-16. IS. by. as:.

(35) 1.3. The solvatochromic. where the. subscript. by using. the solute. nitroaniline).. The. nitrophenol (3) solute. P2. pair formed by probes values. P2. obtain. and. affected. in HBA solvents.. (4). values. are. spectral shifts. those measured when. as. preferred. (Kamlet, 1976).. chemical to the. properties. As in the. other than. U. u. P values,. the. use. and the somewhat solvent. significant scattering. to a. or. diverse. balancing. adoption. of. accounting reliable. a. advises. Pi series,. one. as. picture. against. are. not so. of. clearly. and the acidic groups of the. also be determined. this alternative is seldom. point. by using. adopted. due. in the establishment of both scales. behaviour of. the. defining seems. basicity. the interactions established. some. solute. pairs explains. from the different series of Ui and. originating. basicity. the. measurements used in the calculation of. use. of averaged values which. this would lead to. Uj series in. for the solvent. reference. originating. of the differences. only. experimental. single. can. NR. (Laurence, 1986).. measuring pair. vs.. measurements needed.. family-dependent. of values. dispersion of these results diverse Ui. of. by. probes. scale, Pi values. great complexity of the experimental. and. (N,N-diethyl-4-. to the nature of the. OR donors. when. values. P2. spectral shifts, though. The differential nature of the the. Owing. of its related solute. the. obtaining. basicity vs.. between the oxygen atoms in the nitro group of the. solvent. and 2. P2 values, PI quantifies better the solvent basicity. PI. solvents because the. amphiprotic. (4-nitroaniline). characterizes better the solvent. from this last comment,. Apart. 1. determined from the enhanced solvatochromic shift for 4-. are. PI. .... denotes that this solvent parameter has been evaluated. PI. relative to 4-nitroanisole. pairs used to. donors whereas. 1 in the term. comparison method. a. loss of chemical. from various the solvent. to. Pi values.. are. meaning. and. only. one. rather than. Pi. constitute the best alternative for. of the true variation of these. solvents.. 1-17. microscopic parameters. The. drawn from. experimental measurements;. acidity. the. the. series in. gaining. a. in the different.

(36) 1.4. Solute behaviour. vs.. solvent effect.... i.. 1.4. Solute behaviour. Solvation. The. Energy Relationships (LSER). goal. of all. modifications. of. (Politzer,1994).. The. where XYZ is the. scales of microscopic parameters is their. solvent-dependent. with. the. and. intensity. relationship. expressed. solute. nature. properties. the. interactions. between the solute behaviour and the solvent effect. simple. linear. that present the. models, the so-called linear solvation. following general. in. use. function of the. a. solute/solvent. of the. can. energy. structure:. of this property in. solvent unable to interact with the solute, s, is. solvent parameter. for the variation of the solute property and aj is the. representing. as. subsequent. solvent-dependent solute property, (XYZ)o is the value. hypothetical inert. responsible. in. the. relationships (LSER),. a. empirical. variations. interpreting. often be. solvent effect: the establishment of Linear. vs.. weight. a. regression. coefficient of s,. of the s, contribution to the variation of the solute property XYZ. (Kamlet, 1981), (Reichardt, 1988), (Pytela,1988).. The. simplest. polarity parameter.. LSERs The. are. success. those which correlate. of these. a. uniparametric. solute property with. correlations. (many. only. one. have been. reported using the ET(30) parameter (Reichardt,1982), (Johnson, 1986), (Tunuli,1984)) seems. to be due to the. great similarity between the solvent/probe interactions and the. solvent/solute interactions in the. single probe. particular solvent-dependent. process studied. When. does not represent all the necessary solute/solvent interactions, LSERs. can. a. be. proposed by combining various single parameters whose probes show complementary solute/solvent interactions the donor number. (DN),. (i.e., ET(30), sensitive. sensitive to. to. polarity and hydrogen. to. these combinations is the. between the parameters used due to the presence of of them. acidity. and. polarity and hydrogen bond basicity (Krigowski,1975),. (Wrona, 1991)). The only drawback. some. bond. (e.g., polarity contributions. in. ET(30) 1-18. common. and. DN).. possible. correlation. solute/solvent interactions in.

(37) 1.4. Solute behaviour. solvent effect. vs.. .... The most recommendable alternative for the establishment of multiterm LSERs is the. use. of groups of parameters. interactions. to the. same. parameters in the. same. and. specificity. group. This. yields. specificity. of each parameter allows the direct. Abboud and Taft is the most on a. empirical approach. do). +. XYZ. =. + an +. (XYZ)o. solvents used in the. in its. are. The proven. approach. adequate. Abraham. the. or. same. proposed by Kamlet, for. multiparametric approach. above). or on. can. keep. all. =. LSERs based. expressions. bB of. +. only. some. on. s( 11:*. it, such. property determined and. or. the. describing. + an +. (XYZ)o. reduced. to the solute. According. properties. case. comparison. has led to the. of. underlying philosophy. (Abraham,1993),. where the. of the LSERs. proposal. +. as. to the. of the terms present. tackling. same. the. studied. In this case, the. original expression. method for. of other. same. proposed by. Carr. changes in. =. a. +. bB2 +S11:*2. I-19. +. solvent. L d.x i2. the. the. original. supposed. to be. and. measured property in are. described. a. using. empirical parameters. of Kamlet, Abboud and Taft. The. (XYZ)o + aa.2. as. (Li,1991), (Carr,1993). becomes then:. XYZ. problem. the XYZ property. descriptors instead of the. explaining. general expressions. kind of formulation is. where solute-to-solute variations of. linear models which contain solute present in the. i.e., the. of the contribution of each. method. comparison. the linear model XYZ. expressions. analogous problems. are. interpretation. of the solvatochromic. success. This is the. fixed solvent. clearer chemical sense,. (Kamlet,1983;1985), (Taft, 1985).. solvent effect in many solute. inspired by. a. (Taft, 1976), (Kamlet,1976;1977). The. on. S11:*.. these. study,. used. in section 1.3 +. bB. extended form. more. based. e1; (described. +. widely. solute property. this. 2. is that each parameter. the contribution of its related solute/solvent interaction to the variation. of the solute property. The solvatochromic. solvent effects. with. minimum correlation with the other. a. correlation between terms, and with. no. as. advantage of working. The. linear models with better mathematical features,. i.e., with. term to the model. solvent/solute. specific. original multiparametric approach. to have a maximum. designed. h�. to cover all the. (Kamlet,1981), (Swain,1983), (Drago, 1992).. parameters belonging is. proposed jointly. general equation.

(38) 1.4. Solute behaviour vs. solvent effect.... where the. 2 indicates that the. subscript. and n*2 are then the solute. and. which. descriptors. approach applied.. U2,. 132. L djxj2. depend. on. variables. solute. hydrogen-bond acidity,. polarity-polarizability, respectively, additional solute. independent. are. solute. descriptors.. hydrogen-bond basicity and. the. empirical. the process. analyzed. same. and. chemical. on. in both. meaning. owing. to the different. Abboud. methodologies employed in determining then (Politzer,1994). Merging the Kamlet, expression,. which works with. series of solvents, with the last. of solutes in and. a. fixed solvent,. solvent-paired properties. of. measures. a. property for. solute in. one. series. general equation with crossed-terms showing the. solute. which handles. measures. of a property for. a. a. equation,. a more. solute. including. Abraham's and Carr's formulations, have different numerical values. and Taft basic. 132. U2,. other terms in the model. n*2' while sharing the. and. are. involved in each kind of solute/solvent interaction. can. be. obtained.. Subscripts can. a. I and 2 denote solvent and solute. properties, respectively.. be used to describe variations of a property measured for. This. equation. series of solutes dissolved in. a. series of solvents (Kamlet, I 985).. A recent alternative to all these. solvation. energy. (Famini,1989;1992).. relationships These. are. classical LSERs, in which the theoretical. expressions. models with the. from. molecular. (Lowrey,1995). Modelled after the experimental have been. designed. to correlate. obtain theoretical models which can. work in. a. wide range of. closely are as. applications.. as. by. Famini. are. substituted. computational. empirical pattern descriptors. possible. to the. Wilson. structure and aim as the. descriptors. orbital. and. LSER parameters, the TLSER. with their. similar. the so-called theoretical linear. same. solute and/or solvent. empirical. descriptors determined. are. proposed. (TLSER),. general. above. original. by. methods. descriptors in order to. LSERs and which. Within the domain of linear models. using. theoretical. descriptors, Murray. named the. general interaction properties function (GIPF) (Murray,1994) (Politzer, 1 994).. and Politzer have. 1-20. developed. a. rather innovative. approach.

(39) 1.4. Solute behaviour vs. solvent effect. Although it. shares the. property and are. goal of seeking. quantitative. a. microscopic descriptors,. some. not related to those used in LSERs. The. linear. between. relationship. aIPF works with theoretical. general. certain. a. descriptors. formulation of the aIPF. .... which. approach is. as. follows:. -. Property. where. _ -. f[ surface area, IS,min,. VS,max, V S,min, II, 0'101. IS,min reflects the tendency for charge transfer,. range attraction for. polarity, 0'1012. nucleophiles. for the. and. variability. in the. such. contributions, available. interpretation. of the surface electrostatic. as. means. the determination of solvent. experimentally and,. and their related. by. properties. what is. or. interesting,. more. v]. for molecules yet to be. of. indicators of long. and. potential. approaches. weighted. solute. the. are. II accounts for the local. electrophiles, respectively,. of processes. ,. VS,max and V S,min. "electrostatic balance" term. The evolution of these theoretical. possibilities. 2. sums. descriptors. prediction. synthesized,. thus. v. is. opens up. of. an. new. microscopic. which. of these. are. not. descriptors. contributing. to the. intelligent design of molecules for special purposes.. In the. proposal. of any theoretical. or. empirical LSER,. effort must be focused. on. the. correct establishment of the linear model that will afterwards be used to understand the. solute/solvent interactions. responsible. the values of this property,. pointed. out. by. terms in these. once. for the variation of. the suitable solute. most of the authors who have. or. a. certain property and to. solvent. proposed general. expressions must necessarily be included to. descriptors. are. predict. known. As. LSER models, not all the. describe the variation of the XYZ. property of interest (Kamlet, 1981), (Reichardt,1988). The existence and weight of the different contributions included in the LSER XYZ property and also of the. generalized use. on. the solutes and solvents. of LSERs, the. often tended to work with the whole each of their terms for the. methodology these. led. expressions. some. proposed. will. depend. on. employed in its study.. procedures applied 4I establishing original expressions regardless. description. the nature of the At the. these linear models. of the. of the solute property under. significance. study.. scientists to cast reasonable doubts upon the chemical. and to consider LSERs. as. local. 1-21. empirical. beginning. rules rather than. This. rough. meaning. as. of. of. behaviour.

(40) 1.4. Solute behaviour vs. solvent effect.... models structured. Actually, with. these. early. limited. a. as. combinations of fundamental. overfitted models do not go. model. methodologies. are. valuable. many different. of. that. significance. enlighten. methods that. to. the intrinsic. meaning,. expressions of their. quality. the LSERs established. using. of each of the terms included in the or. solvent effect. on. Two. strategies. quality. of LSERs is. with rather different. methods that fit the. experimental. one. backgrounds. data to. a. of the. are. concerns. proposed:. postulated. the. of. use. chemical model,. where the final model is built without the. use. expression.. Hard-modelling methods. All the. procedures included within this. group share the need of. model to be used in the establishment of the LSER. When the handled in the. (Sjostrom.Ivs l).. the category of local. the nature of the solute. the. can ensure. application of soft-modelling methods,. of any initial basic. 1.4.1.. which check the. expressions. project.. hard-modelling. and the. and to their sound chemical. effects. properties (Kamlet,1985).. Identifying the present. beyond. predictive ability. Nevertheless, owing. microscopic descriptors reliable. microscopic. are. case. related to the variations of a solute property in. of the. examples presented. Abboud and Taft, XYZ. =. (XYZ)o +. in this. au +. b�. +. a. descriptors. they. as. highly suitable initial model.. a. descriptors. are. of Kamlet,. sn*, is. in the initial model have been can. be carried out. This. to be included in the LSER. A. used to determine which of the solvent. be present in the LSER. This. procedure is. backward elimination of variables, the solvent. data to be. the reduced. expression. general. following steps:. 1. Selection of the solvent. procedure is. experimental. series of solvents,. certain solvent set, the establishment of the LSER. process includes the. initial. project,. Once the solute property and the solvent. determined for. a. an. as. a. descriptors. stepwise. in the initial model must. combination of forward selection and. proposed by Forina et al. (Forina,1988). First of all,. descriptor showing the largest correlation with the 1-22. solute property is selected.

(41) 1.4. Solute behaviour vs. solvent effect. as. the first. independent. independent variable,. variable in the LSER. Before the introduction of. two statistical F-tests. are. value is calculated for each non-entered solvent the. new. computed.. descriptor to. In the. calculated to. see. an. F-to-delete. if any of the. value, smaller than the. already selected. variables. This process continues until any of the non-selected. can. an. new. F-to-enter. check if the introduction of. descriptor causes a significant decrease in the variance. fit; in the second,. first,. a. .... associated with the model. F value in the first test, is. be removed from the model.. descriptors give F. values. larger than. the control F value.. 2. Detection and removal of the outliers. present in the data. set. Once the solute. property (dependent variable) and the suitable solvent descriptors (independent variables) have been. selected,. approach allows. a. least median of squares. the detection of outliers. through. residuals. A function of these residuals is also. is. regression (LMS) the. applied. study. This robust. applied.. of the standardized LMS. in the robust. diagnostic. method. proposed by Rousseeuw and Leroy (Rousseeuw,1981) for outlier detection. Only data detected. as. outliers. by both previous methods. order to avoid the exclusion of good. have been removed from the data set in. leverage points. 3. Establishment of the definitive LSER model. A. selected solvent. precautions. taken in the. last. control. quality. without. descriptors,. previous steps. including. included in the model and. a. an. least-squares. including. To obtain to. confirm the. significance. of the variance. to. Despite. the the. of a correct LSER,. a. of each of the terms. support the existence of. descriptors. is. performed. on. a. the. expression.. a. clearer idea of the. provide information regarding. quality of the LSERs established,. the number of. points. of the correlation, such. as. 1-23. error. referring. the residual standard deviation. coefficient.. it is recommendable. in the data set, the. with each of the coefficients in the model and certain parameters. quality. performed with. the detected outliers.. correlation between the solute property and the solvent definite LSER. fit is. to ensure the establishment. r-test to. analysis. from the definitive model.. or. associated. to the. global. the correlation.

(42) 1.4. Solute behaviour. 1.4.2.. vs.. solvent effect.... Soft-modelling methods.. These model-free methods work with multivariate establishment of. general. variety. of. Factor. Analysis (TFA). multivariate data sets. proposed. the combination of Factor. here. given. its great. the establishment of. through. ability. meaningful. and allow the. sets. LSERs without the need of any initial model.. soft-modelling procedures, is. data. Among the wide. Analysis (FA). and. Target. to describe the variation of. linear models. (Malinowski,. 1991).. The. property solutes. experimental. are. are. data. required. measurements of the. in. the solvent effect. understanding. property under study in. a. solute. often used to record these series of measurements in order to avoid biased. solute. owing to. was. performed. with. its concrete features. The measurements obtained for the different. solutes in the selected solvent set. Figure. a. certain solvent set. Several. conclusions about the solvent effect which could arise if the research. only one. on. can. be structured to form. a. data matrix,. as. shown in. 1.4.2.1.. Solute 1. Solute 2. Solute. Solvent 1. n. a. 1n. Solvent 2. Solvent. m. a. a mn. m1. Figure 1.4.2.1. Arrangement of solvent-dependent arrays of data to form value of an experimental property for the solute j dissolved in the solvent i.. a. data matrix. aij represents the. Each column in the data matrix is the array of data collected for. hence,. a. solvent-dependent. variation is present. 1-24. along. a. certain solute;. the columns of the data matrix.

(43) 1.4. Solute behaviour vs. solvent effect. whereas solute-to-solute differences. are. for the variation detected. responsible. .... the. along. rows.. Factor. Analysis. is. a. frequently used technique. for. of variation in the data matrices. This chemometrical data matrix D. pT (n. c),. x. sources. (r. x. c). into the. product. of the. whose column vectors and. of variation. (factors) along. scores. vector PI. by. the outer. products. (r. x. n) and. can. of each. along. the. score. vector. of the. by. matrix. abstract. original. data. series of additive. as a. t,. original. loadings. independent. n. rows. be rewritten. the. causes. its related. loading. T .. Hence, the application of FA only makes. bilinear, i.e., if it sources. matrix T. the columns and. the. procedure decomposes. vectors describe the. row. matrix, respectively. This matrix decomposition contributions formed. interpreting the underlying. can. be described with. a. sense. if the. original. data matrix is. intrinsically. model of additive contributions related to the real. of variation in the data.. a) D. I. I. I. I. 'T' I I. � -. t1. Itn b). p2T. p1T D. +. t1. decomposition ofa data matrix as a) product of scores sum of the outer products of related scores and loading vectors.. Figure. pnT. 1.4.2.2. FA. 1-25. and. loadings. matrices and. b). as a.

(44) 1.4. Solute behaviour. The. vs.. scores. and. covariance matrix Z. finding a Q matrix. solvent effect.. =. are. matrix T. Q. are. the. eigenvector. when. loadings matrix, pT,. of the Z matrix and the elements in the A.. eigenvectors. of its related. be. by. such that. The. can. of the. diagonalization. DTD associated with the D matrix. This process is carried out. eigenvalues.. to the. calculated from the. are. their related. importance equal. matrices. loading. The columns of matrix. ... and. magnitude describing. owing to. the. of each. eigenvalue. is linked to the. the variation of the D matrix.. orthogonality of the Q matrix,. the. T. Q is scores. simply calculated as. T=DQ. Due to the process followed in the FA. always the. a. row. lack of correlation among the column vectors in the. vectors in the. When score vectors. are. parameter. The elements in. the. that shown in. abstract solvent. actually. solvent features but cannot be. variations of. as. Figure. represent independent solvent contributions. descriptor for. a. directly. abstract solvent of this abstract. the. original. solvent-dependent property. simplest. a. scores. data. matrix, there is. matrix T and among. 1.4.2.1. is. descriptors. weights. a. by. vector. a. vector. containing. the. they depend. on. the. solvent. of their related abstract solvent. original. series of. model of additive contributions formed. descriptor. because. chemically meaningful. data set. The. measured in. factor-analyzed,. to the overall variation of the data. identified with any. loading vector are. each of the solutes in the. a. of. loadings matrix pT.. data matrix such. a. matrix. These vectors. by using. decomposition. the. by. data matrix. solutes) is. the outer. (i.e.,. then defined. products. solute-weighted. the. of. an. contributions. descriptor on the variation of the property under study.. The FA. decomposition of. indeed, by looking. at the. Figure. a. data matrix recalls the structure of. 1.4.2.3. it. can. 1-26. be. seen. an. that both ways of. LSER. model;. expressing. the.

(45) 1.4. Solute behaviour. original matrix. data matrix share. as a sum. of FA and. product of. exactly. coefficients to. same. form. FA and LSER describe the. of solute-weighted contributions of solvent. chemically meaningful a. the. matrix of solvent. vs.. in the LSER. model). descriptors by. a. a more. containing. .... original. data. in the. case. descriptors (abstract. or, in. matrix. solvent effect. compact way, their related. as. the. weight. explain the overall variation of the data matrix.. a) .... �. weight coefficients. 'c. 0 III. Q) '0. D. 'E. =. Q). � �. _l T. b) .... weight coefficients. �. 'c. &l. Q). D. '0. =. C Q). � iii. I!!. s. Figure. 1.4.2.3. Data matrix. Though. description by using the. FA describes. perfectly. FA. decomposition or an LSER model.. the variation of the. abstract model, the ideal situation would be to find. solvent. descriptors. could be transformed into. Target Factor Analysis (TFA). is. a. a. experimental. procedure by which the. chemically meaningful. technique whose main goal. is. application. steps listed below, and which. are. of FA and TFA. later. to. establish. determining the. explained in detail.. 1-27. an. an. abstract. solvent parameters.. between the domain of abstract solutions and the domain of real solutions. The combined. data with. connection. (exemples,).. LSER model includes the.