HANDBOOK OF SOLVENTS
Preface.
Although the chemical industry can trace its roots into antiquity, it was during the industrial
revolution that it started to become an actual industry and began to use the increased knowledge
of chemistry as a science and technology to produce products that were needed by
companion industries and consumers. These commercial efforts resulted in the synthesis of
many new chemicals. Quite quickly, in these early days, previously unknown materials or
materials that had been present only in low concentrations, were now in contact with people
in highly concentrated forms and in large quantities. The people had little or no knowledge
of the effects of these materials on their bodies and the natural biological and physical
processes in the rivers and oceans, the atmosphere, and in the ground.
Until the end of the nineteenth century these problems were not addressed by the
chemical industry and it is only recently that the industry began to respond to public criticism
and political efforts. Legal restrictions aimed at preserving the quality of life have been
directed at health, safety and longevity issues and the environment. Solvents have always
been mainstays of the chemical industry and because of their widespread use and their high
volume of production they have been specifically targeted by legislators throughout the
world. The restrictions range from total prohibition of production and use, to limits placed
on vapor concentrations in the air. As with any arbitrary measures some solvents have been
damned unfairly. However, there is no question that it is best to err on the side of safety if the
risks are not fully understood. It is also true that solvents should be differentiated based on
their individual properties.
This book is intended to provide a better understanding of the principles involved in
solvent selection and use. It strives to provide information that will help to identify the risks
and benefits associated with specific solvents and classes of solvents. The book is intended
to help the formulator select the ideal solvent, the safety coordinator to safeguard his or her
coworkers, the legislator to impose appropriate and technically correct restrictions and the
student to appreciate the amazing variety of properties, applications and risks associated
with the more than one thousand solvents that are available today.
By their very nature, handbooks are intended to provide exhaustive information on the
subject. While we agree that this is the goal here, we have attempted to temper the impact of
information, which may be too narrow to make decision.
Many excellent books on solvents have been published in the past and most of these
are referenced in this book. But of all these books none has given a comprehensive overview
of all aspects of solvent use. Access to comprehensive data is an essential part of solvent
evaluation and it has been a hallmark of such books to provide tables filled with data to the
point at which 50 to 95% of the book is data. This approach seems to neglect a fundamental
requirement of a handbook - to provide the background, explanations and clarifications that
are needed to convert data to information and assist the reader in gaining the knowledge to
make a decision on selecting a process or a solvent. Unfortunately, to meet the goal of providing
both the data and the fundamental explanations that are needed, a book of 4,000 to
5,000 pages might be required. Even if this was possible, much of the data would fall out of
date quite quickly. For example, a factor that defines solvent safety such as threshold limit
values (TLVs) for worker exposure or some single toxicity determinants may change
frequently. This book would be huge and it would have to be updated frequently to continue
to claim that it is current.
What we have attempted to do here is to give you a book with a comprehensive and extensive
analysis of all current information on solvents then use other media to present the
supporting data on individual solvents. These data are provided on a CD-ROM as a
searchable database. Data are provided on more than 1140 solvents in 110 fields of data.
The medium permits frequent updates. If the same data were presented in book form, more
than 2,000 pages would be needed which exceeds the size of any data in handbook form
offered to date.
The best approach in presenting an authoritative text for such a book is to have it written
by experts in their fields. This book attracted well-known experts who have written
jointly 47 books and authored or coauthored hundreds of papers on their areas of expertise.
The authors have made their contributions to this book in late 1999 and early 2000
providing the most current picture of the technology. Their extreme familiarity with their
subjects enables them to present information in depth and detail, which is essential to the
reader’s full understanding of the subject.
The authors were aware of the diversity of potential readers at the outset and one of
their objectives was to provide information to various disciplines expressed in a way that all
would understand and which would deal with all aspects of solvent applications. We expect
professionals and students from a wide range of businesses, all levels of governments and
academe to be interested readers. The list includes solvent manufacturers, formulators of
solvent containing products, industrial engineers, analytical chemists, government legislators
and their staffs, medical professionals involved in assessing the impact on health of solvents,
biologists who are evaluating the interactions of solvents with soil and water,
environmental engineers, industrial hygienists who are determining protective measures
against solvent exposure, civil engineers who design waste disposal sites and remediation
measures, people in industries where there are processes which use solvents and require
their recovery and, perhaps most important, because understanding brings improvements,
those who teach and learn in our universities, colleges and schools.
A growing spirit of cooperation is evident between these groups and this can be fostered
by providing avenues of understanding based on sharing data and information on common
problems. We hope to provide one such avenue with this book. We have tried to
present a balanced picture of solvent performance by dealing not only with product performance
and ease of processing but also by giving environmental and health issues full consideration.
Data and information on known products and processes should be cornerstones of the
understanding of a technology but there is another aspect of technology, which can lead to
advances and improvements in utility, safety and in safeguarding the environment. This
must come from you, the reader. It is your ideas and creative thinking that will bring these
improvements. The authors have crammed their ideas into the book and we hope these will
stimulate responsible and effective applications of solvents. Francis Bacon wrote, “The end
of our foundation is the knowledge of causes, and the secret motion of things, and the enlarging
of the bound of human Empire, to the effecting of all things possible.”
Today there are few technical activities that do not employ solvents. Almost all industries,
almost all consumer products, almost everything we use can, if analyzed, be shown to
contain or to have used in its processing, a solvent. Solvent elimination need never be a
technical objective. Rather, we need to use our increasing understanding and knowledge to
find the safest and the most effective means of meeting our goals.
I would like to thank the authors for their relentless efforts to explain the difficult in an
interesting way. In advance, I would like to thank the reader for choosing this book and encourage
her or him to apply the knowledge to make our world a better, more livable place.
Table of Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxvii
GEORGE WYPYCH
1 INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
CHRISTIAN REICHARDT
2 FUNDAMENTAL PRINCIPLES GOVERNING SOLVENTS USE . . . . 7
2.1 Solvent effects on chemical systems . . . . . . . . . . . . . . . . . . . . . . . 7
ESTANISLAO SILLA, ARTURO ARNAU, IÑAKI TUÑÓN
2.1.1 Historical outline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.1.2 Classification of solute-solvent interactions . . . . . . . . . . . . . . . . . . . 10
2.1.2.1 Electrostatic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
2.1.2.2 Polarization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
2.1.2.3 Dispersion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
2.1.2.4 Repulsion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
2.1.2.5 Specific interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
2.1.2.6 Hydrophobic interactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2.1.3 Modelling of solvent effects . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.1.3.1 Computer simulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2.1.3.2 Continuum models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2.1.3.3 Cavity surfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
2.1.3.4 Supermolecule models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
2.1.3.5 Application example: glycine in solution . . . . . . . . . . . . . . . . . . . . 23
2.1.4 Thermodynamic and kinetic characteristics of chemical reactions in solution . 27
2.1.4.1 Solvent effects on chemical equilibria . . . . . . . . . . . . . . . . . . . . . . 27
2.1.4.2 Solvent effects on the rate of chemical reactions. . . . . . . . . . . . . . . . . 28
2.1.4.3 Example of application: addition of azide anion to tetrafuranosides. . . . . . . 30
2.1.5 Solvent catalytic effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
2.2 Molecular design of solvents. . . . . . . . . . . . . . . . . . . . . . . . . . . 36
KOICHIRO NAKANISHI
2.2.1 Molecular design and molecular ensemble design . . . . . . . . . . . . . . . . 36
2.2.2 From prediction to design . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
2.2.3 Improvement in prediction method. . . . . . . . . . . . . . . . . . . . . . . . 38
2.2.4 Role of molecular simulation. . . . . . . . . . . . . . . . . . . . . . . . . . . 39
2.2.5 Model system and paradigm for design . . . . . . . . . . . . . . . . . . . . . 40
Appendix. Predictive equation for the diffusion coefficient in dilute solution . 41
2.3 Basic physical and chemical properties of solvents . . . . . . . . . . . . . . . 42
GEORGE WYPYCH
2.3.1 Molecular weight and molar volume. . . . . . . . . . . . . . . . . . . . . . . 43
2.3.2 Boiling and freezing points. . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
2.3.3 Specific gravity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
2.3.4 Refractive index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
2.3.5 Vapor density and pressure. . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
2.3.6 Solvent volatility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
2.3.7 Flash point . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
2.3.8 Flammability limits. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
2.3.9 Sources of ignition and autoignition temperature . . . . . . . . . . . . . . . . 52
2.3.10 Heat of combustion (calorific value) . . . . . . . . . . . . . . . . . . . . . . . 54
2.3.11 Heat of fusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
2.3.12 Electric conductivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
2.3.13 Dielectric constant (relative permittivity) . . . . . . . . . . . . . . . . . . . . 54
2.3.14 Occupational exposure indicators . . . . . . . . . . . . . . . . . . . . . . . . 56
2.3.15 Odor threshold . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
2.3.16 Toxicity indicators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
2.3.17 Ozone-depletion and creation potential . . . . . . . . . . . . . . . . . . . . . 58
2.3.18 Oxygen demand . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
2.3.19 Solubility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
2.3.20 Other typical solvent properties and indicators . . . . . . . . . . . . . . . . . 60
3 PRODUCTION METHODS, PROPERTIES,
AND MAIN APPLICATIONS . . . . . . . . . . . . . . . . . . . . . . . . . 65
3.1 Definitions and solvent classification . . . . . . . . . . . . . . . . . . . . . . 65
GEORGE WYPYCH
3.2 Overview of methods of solvent manufacture . . . . . . . . . . . . . . . . . . 69
GEORGE WYPYCH
3.3 Solvent properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
GEORGE WYPYCH
3.3.1 Hydrocarbons. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
3.3.1.1 Aliphatic hydrocarbons. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
3.3.1.2 Aromatic hydrocarbons. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
3.3.2 Halogenated hydrocarbons . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
3.3.3 Nitrogen-containing compounds (nitrates, nitriles) . . . . . . . . . . . . . . . 79
3.3.4 Organic sulfur compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
3.3.5 Monohydric alcohols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
3.3.6 Polyhydric alcohols. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
3.3.7 Phenols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
3.3.8 Aldehydes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
3.3.9 Ethers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
3.3.10 Glycol ethers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
3.3.11 Ketones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
3.3.11 Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
3.3.12 Amines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
3.3.13 Esters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
3.3.14 Comparative analysis of all solvents . . . . . . . . . . . . . . . . . . . . . . . 94
3.4 Terpenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
TILMAN HAHN, KONRAD BOTZENHART, FRITZ SCHWEINSBERG
3.4.1 Definitions and nomenclature . . . . . . . . . . . . . . . . . . . . . . . . . . 96
3.4.2 Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
3.4.3 General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
3.4.4 Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
3.4.5 Threshold limit values . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
4 GENERAL PRINCIPLES GOVERNING DISSOLUTION
OF MATERIALS IN SOLVENTS. . . . . . . . . . . . . . . . . . . . . . . 101
4.1 Simple solvent characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . 101
VALERY YU. SENICHEV, VASILIY V. TERESHATOV
4.1.1 Solvent power . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
4.1.2 One-dimensional solubility parameter approach. . . . . . . . . . . . . . . . . 103
4.1.3 Multi-dimensional approaches . . . . . . . . . . . . . . . . . . . . . . . . . . 110
4.1.4 Hansen’s solubility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
4.1.5 Three-dimensional dualistic model. . . . . . . . . . . . . . . . . . . . . . . . 116
4.1.6 Solubility criterion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
4.1.7 Solvent system design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
4.2 Effect of system variables on solubility . . . . . . . . . . . . . . . . . . . . . 124
VALERY YU. SENICHEV, VASILIY V. TERESHATOV
4.2.1 General considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
4.2.2 Chemical structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
4.2.3 Flexibility of a polymer chain . . . . . . . . . . . . . . . . . . . . . . . . . . 127
4.2.4 Crosslinking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
4.2.5 Temperature and pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
4.2.6 Methods of calculation of solubility based on thermodynamic principles. . . . 130
Fundamental Principles
Governing Solvents Use
2.1 SOLVENT EFFECTS ON CHEMICAL SYSTEMS
2.1.1 HISTORICAL OUTLINE
According to a story, a little fish asked a big fish about the ocean, since he had heard it being
talked about but did not know where it was. Whilst the little fish’s eyes turned bright and
shiny full of surprise, the old fish told him that all that surrounded him was the ocean. This
story illustrates in an eloquent way how difficult it is to get away from every day life, something
of which the chemistry of solvents is not unaware.
The chemistry of living beings and that which we practice in laboratories and factories
is generally a chemistry in solution, a solution which is generally aqueous. A daily routine
such as this explains the difficulty which, throughout the history of chemistry, has been encountered
in getting to know the effects of the solvent in chemical transformations, something
which was not achieved in a precise way until well into the XX century. It was
necessary to wait for the development of experimental techniques in vacuo to be able to separate
the solvent and to compare the chemical processes in the presence and in the absence
of this, with the purpose of getting to know its role in the chemical transformations which
occur in its midst. But we ought to start from the beginning.
Although essential for the later cultural development, Greek philosophy was basically
a work of the imagination, removed from experimentation, and something more than meditation
is needed to reach an approach on what happens in a process of dissolution. However,
in those remote times, any chemically active liquid was included under the name of “divine
water”, bearing in mind that the term “water” was used to refer to anything liquid or dissolved.
1
Parallel with the fanciful search for the philosopher’s stone, the alchemists toiled
away on another impossible search, that of a universal solvent which some called “alkahest”
and others referred to as “menstruum universale”, which term was used by the very
Paracelsus (1493-1541), which gives an idea of the importance given to solvents during that
dark and obscurantist period. Even though the “menstruum universale” proved just as elusive
as the philosopher’s stone, all the work carried out by the alchemists in search of these
illusionary materials opened the way to improving the work in the laboratory, the development
of new methods, the discovery of compounds and the utilization of novel solvents.
One of the tangible results of all that alchemistry work was the discovery of one of the first
experimental rules of chemistry: “similia similibus solvuntor”, which reminds us of the
compatibility in solution of those substances of similar nature.
Even so, the alchemistry only touched lightly on the subject of the role played by the
solvent, with so many conceptual gulfs in those pre-scientific times in which the terms dissolution
and solution referred to any process which led to a liquid product, without making
any distinction between the fusion of a substance - such as the transformation of ice into liquid
water -, mere physical dissolution - such as that of a sweetener in water - or the dissolution
which takes place with a chemical transformation - such as could be the dissolution of a
metal in an acid. This misdirected vision of the dissolution process led the alchemists down
equally erroneous collateral paths which were prolonged in time. Some examples are worth
quoting: Hermann Boerhaave (1688-1738) thought that dissolution and chemical reaction
constituted the same reality; the solvent, (menstruum), habitually a liquid, he considered to
be formed by diminutive particles moving around amongst those of the solute, leaving the
interactions of these particles dependent on the mutual affinities of both substances.2 This
paved the way for Boerhaave to introduce the term affinity in a such a way as was conserved
throughout the whole of the following century.3 This approach also enabled Boerhaave to
conclude that combustion was accompanied by an increase of weight due to the capturing of
“particles” of fire, which he considered to be provided with weight by the substance which
was burned. This explanation, supported by the well known Boyle, eased the way to considering
that fire, heat and light were material substances until when, in the XIX century, the
modern concept of energy put things in their place.4
Even Bertollet (1748-1822) saw no difference between a dissolution and a chemical
reaction, which prevented him from reaching the law of definite proportions. It was Proust,
an experimenter who was more exacting and capable of differentiating between chemical
reaction and dissolution, who made his opinion prevail:
“The dissolution of ammonia in water is not the same as that of
hydrogen in azote (nitrogen), which gives rise to ammonia”5
There were also alchemists who defended the idea that the substances lost their nature
when dissolved. Van Helmont (1577-1644) was one of the first to oppose this mistaken idea
by defending that the substance dissolved remains in the solution in aqueous form, it being
possible to recover it later. Later, the theories of osmotic pressure of van´t Hoff (1852-1911)
and that of electrolytic dissociation of Arrhenius (1859-1927) took this approach even further.
Until almost the end of the XIX century the effects of the solvent on the different
chemical processes did not become the object of systematic study by the experimenters. The
effect of the solvent was assumed, without reaching the point of awakening the interest of
the chemists. However, some chemists of the XIX century were soon capable of unraveling
the role played by some solvents by carrying out experiments on different solvents, classified
according to their physical properties; in this way the influence of the solvent both on
chemical equilibrium and on the rate of reaction was brought to light. Thus, in 1862,
Berthelot and Saint-Gilles, in their studies on the esterification of acetic acid with ethanol,
8 Estanislao Silla, Arturo Arnau and Iñaki Tuñón
discovered that some solvents, which do not participate in the chemical reaction, are capable
of slowing down the process.6 In 1890, Menschutkin, in a now classical study on the reaction
of the trialkylamines with haloalcans in 23 solvents, made it clear how the choice of
one or the other could substantially affect the reaction rate.7 It was also Menschutkin who
discovered that, in reactions between liquids, one of the reactants could constitute a solvent
inadvisable for that reaction. Thus, in the reaction between aniline and acetic acid to produce
acetanilide, it is better to use an excess of acetic acid than an excess of aniline, since the
latter is a solvent which is not very favorable to this reaction.
The fruits of these experiments with series of solvents were the first rules regarding the
participation of the solvent, such as those discovered by Hughes and Ingold for the rate of
the nucleophilic reactions.8 Utilizing a simple electrostatic model of the solute - solvent interactions,
Hughes and Ingold concluded that the state of transition is more polar than the
initial state, that an increase of the polarity of the solvent will stabilize the state of transition
with respect to the initial state, thus leading to an increase in the reaction rate. If, on the contrary,
the state of transition is less polar, then the increase of the polarity of the solvent will
lead to a decrease of the velocity of the process. The rules of Hughes-Ingold for the
nucleophilic aliphatic reactions are summarized in Table 2.1.1.
Table 2.1.1. Rules of Hughes-Ingold on the effect of the increase of the polarity of the
solvent on the rate of nucleophilic aliphatic reactions
Mechanism Initial state State of transition Effect on the reaction rate
SN2
Y- + RX [Y--R--X]- slight decrease
Y + RX [Y--R--X] large increase
Y- + RX+ [Y--R--X] large decrease
Y + RX+ [Y--R--X]+ slight decrease
SN1
RX [R--X] large increase
RX+ [R--X]+ slight decrease
In 1896 the first results about the role of the solvent on chemical equilibria were obtained,
coinciding with the discovery of the keto-enolic tautomerism.9 Claisen identified the
medium as one of the factors which, together with the temperature and the substituents,
proved to be decisive in this equilibrium. Soon systematic studies began to be done on the
effect of the solvent in the tautomeric equilibria. Wislicenus studied the keto-enolic equilibrium
of ethylformylphenylacetate in eight solvents, concluding that the final proportion between
the keto form and the enol form depended on the polarity of the solvent.10 This effect
of the solvent also revealed itself in other types of equilibria: acid-base, conformational,
those of isomerization and of electronic transfer. The acid-base equilibrium is of particular
interest. The relative scales of basicity and acidity of different organic compounds and homologous
families were established on the basis of measurements carried out in solution,
fundamentally aqueous. These scales permitted establishing hypotheses regarding the effect
of the substituents on the acidic and basic centers, but without being capable of separating
this from the effect of the solvent. Thus, the scale obtained in solution for the acidity of
the a-substituted methyl alcohols [(CH3)3COH > (CH3)2CHOH > CH3CH2OH > CH3OH]11
came into conflict with the conclusions extracted from the measurements of movements by
NMR.12 The irregular order in the basicity of the methyl amines in aqueous solution also
proved to be confusing [NH3 < CH3NH2 < (CH3)2NH > (CH3)3N],13 since it did not match
any of the existing models on the effects of the substituents. These conflicts were only resolved
when the scales of acidity-basicity were established in the gas phase. On carrying out
the abstraction of the solvent an exact understanding began to be had of the real role it
played.
The great technological development which arrived with the XIX century has brought
us a set of techniques capable of giving accurate values in the study of chemical processes in
the gas phase. The methods most widely used for these studies are:
• The High Pressure Mass Spectrometry, which uses a beam of electron pulses14
• The Ion Cyclotron Resonance and its corresponding Fourier Transform (FT-ICR)15
• The Chemical Ionization Mass Spectrometry, in which the analysis is made of the
kinetic energy of the ions, after generating them by collisions16
• The techniques of Flowing Afterglow, where the flow of gases is submitted to
ionization by electron bombardment17-19
All of these techniques give absolute values with an accuracy of ±(2-4) Kcal/mol and
of ±0.2 Kcal/mol for the relative values.20
During the last decades of XX century the importance has also been made clear of the
effects of the solvent in the behavior of the biomacromolecules. To give an example, the influence
of the solvent over the proteins is made evident not only by its effects on the structure
and the thermodynamics, but also on the dynamics of these, both at local as well as at
global level.21 In the same way, the effect of the medium proves to be indispensable in explaining
a large variety of biological processes, such us the rate of interchange of oxygen in
myoglobin.22 Therefore, the actual state of development of chemistry, as much in its experimental
aspect as in its theoretical one, allows us to identify and analyze the influence of the
solvent on processes increasingly more complex, leaving the subject open for new challenges
and investigating the scientific necessity of creating models with which to interpret
such a wide range of phenomena as this. The little fish became aware of the ocean and began
explorations.
