\r\n\tIncreasingly, governments and development institutions are recognizing the importance of addressing social exclusion for sustainable development. As such, the book will examine the role of government and the contribution of international development partners in the protection and support of marginalized groups and communities. Additionally, the role, responsibility, and response of academia as a socially accountable partner will form part of the discourse.
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The purposes of this chapter are twofold. First, the thermodynamics fundaments are studied in detail to determine experimentally, calculate and interpret thermodynamic partial molar properties using different titration techniques. Second, the postgraduate students are provided with the necessary thermodynamic background to extract behavioural trends from experimental techniques including densimetry, sound speed measurement and isothermal titration calorimetry.
The first concept introduced in this chapter is “thermodynamic description”. It is defined as a set of variables employed to define thermodynamically the studied system. For example, a description by components of a multicomponent system is:
where J is an extensive thermodynamic property; n1, n2 and n3 are the number of moles of components 1, 2 and 3. Other type of thermodynamic description is in terms of the concept of “fraction of a system”. A fraction of a system is a thermodynamic entity, with internal composition, which groups several components. For example, the above-mentioned system can be considered as being composed of the component 1, and a fraction F grouping components 2 and 3. In this way, J can be written as:
where nF is the total number of moles of the fraction F and xf3 is a variable related to the composition of the fraction. Depending on the system, one can choose the more adequate description. For example, in a liquid mixture, a description by components (Eq. (1)) can be suitable. Other systems as those shown in Figure 1 could be better described in terms of fractions.
Examples of different descriptions in two systems. (A) and (B) are several solutes in a solvent. (C) and (D) are a functionalized latex with polar groups.
Figure 1A shows a system composed of the solvent (component 1), solute A (component 2) and solute B (component 3). This system will be described in this chapter using a description by fractions representing a “complex solute” composed of solutes A and B (see Figure 1B). This description is appropriate to use in conditions of infinite dilution and dilute solutions. Other example (see Figure 1C and D) is a functionalized latex particle. A latex is a system composed of polymeric particles dispersed in a solvent. In a functionalized latex, particles are composed of non-polar groups and of functional groups (usually polar groups). In this case, a description by components expressed in Eq. (1) and visualized in Figure 1C is very difficult to use and it is more convenient to consider a fraction (polymeric particle) composed of non-polar groups (component 2) and of polar groups (component 3). Figure 1D shows a sketch of this description.
When different descriptions are considered for a system, we have to reconsider the relation between the description and the thermodynamic object studied. In principle, one might think that all descriptions are equivalent. But this is not true because not all descriptions can retain all features of a thermodynamic system. For example, it is not possible to speak about thermodynamic partial properties at infinite dilution in multicomponent systems. This fact should not be surprising because in differential geometry [1] there is the same problem associated with the relation between a parametrization and a geometric object. Let’s consider, for example, the sphere of radius equal to one, and a parametrization is:
The problem with this parametrization is that it only covers the top half of the sphere. In addition, it is not differentiable in the points of the sphere’s equator. Other possibility is:
But, it only covers the lower half of the sphere and neither is differentiable in points of the sphere’s equator. Even if we consider a combination of X1 and X2, we have the problem of the lack of differentiability in the points of the sphere’s equator. Another possible parametrization is:
where θ is the colatitude (the complement of the latitude) and ϕ the longitude. X3 covers the whole surface of the sphere and it is also differentiable in all points. For this reason, it contains more information about the sphere (geometric object) than X1 and X2. Backing to thermodynamics, in the same case than for X3, the partial molar properties at infinite dilution cannot be obtained and manipulated using the description by components, and it is necessary to use the description by fractions.
The other concept also introduced in this chapter is the “interaction between components of a system”. The first principle of thermodynamics establishes the way, in which systems interact between them and/or with surroundings. In this case, we are interested in the interaction inside the systems and this cannot be interpreted macroscopically using the first principle of thermodynamics. With the concept of interaction between components, we can define mathematically a dilute solution and characterize its thermodynamic behaviour in terms of molar partial properties. In addition to this, we will consider the partial molar properties at infinite dilution. These properties are essential in studies of polymeric particles because they contain the information about the interactions inside the particles. These interactions determine the architecture and final application of the particle.
In this section, some mathematical tools are presented such as changes of variable, changes of size, the Euler theorem and limits in multivariable functions. Variable changes will allow us to relate partial properties of different descriptions. Changes of size are the processes underlying the extensivity and non-extensivity of thermodynamic properties, which will be mathematically implemented by the concept of homogeneity. The Euler’s theorem will be treated in the more general form, and in its demonstration we will avoid some aspects, which remain unclear in the versions of the textbooks of Callen [2] and Klotz and Rosenberg [3].
Let f be the function defined as:
The gradient of f with respect to the variables x1, x2 and x3 is the vector:
If we consider the change of variable:
the function f will take the form:
where its gradient will be:
Our interest is to relate the partial derivatives with respect to the variables x1, x2 and x3 given in Eq. (7) with the partial properties with respect to y1, y2 and y3 given in Eq. (10). From Eq. (8), the total differential of x1 is:
Using dx1 given by Eq. (11) and similarly with equations for dx2 and dx3, we can write:
where the matrix T is:
From (6) and using (7), the total differential of f can be expressed as:
where the symbol “T” indicates “transpose”. From Eq. (9) using Eq. (10), the differential of f can be written as:
Equaling (15) to (14) and using (12):
Remembering that x being a vector and A a matrix, then (xT A)T = AT x, and taking the transpose in both sides of (16):
Eq. (17) relates the vector gradient with respect to the variables (x1, x2, x3) to the vector gradient with respect to the variables (y1, y2, y3), and it will allow us to express the partial properties in two different descriptions.
In this paragraph, the process of size change in thermodynamic systems is analyzed. The behaviour of systems in a size change has consequences on the behaviour or nature of the thermodynamic properties as well as on the form of the thermodynamic equations of the system. Figure 2 shows a visualization of this process in both directions: increasing and reduction.
Sketch of the change of size (increasing and reduction) of a system with volume V.
From Figure 2, it is clear that being V the volume, N the number of moles and U the internal energy, the configuration of this system is, under increasing size λ times:
Thermodynamic properties, which transform accordingly to (18), depend on the size of the system and are named extensive variables. Not all thermodynamic variables transform according to Eq. (18). An example is the molar fraction of the component 2 (x2) in a two-component system. We can see this formally in the following way. For a two-component system:
and x2 transforms as:
That is, the molar fraction of the component 2 is independent of the system size. Properties, which remain constant upon size change, are named intensive properties. Other thermodynamic properties with such characteristics are temperature, pressure, pH and concentration c2 (c2 = N2/V). It is also interesting to look at the behaviour of functions, which depend on thermodynamic variables (intensive and/or extensive), in a size change. Let, for example, the function f be given by f = f(T, P, N1, N2, …). For particular values of the variables T0, P0, N01, N02, …, the function f takes the value f0, and in a change of size:
If
In this case, f is a homogeneous function of one degree. If
Let f = f(x1, x2,…; y1, y2,…) be a function, which is a homogeneous function of one degree with respect to the variables y1, y2,…:
Then,
The demonstration is as follows. The differential with respect to λ in the left side of (24) is:
For the sets of variables x1, x2,… and y1,y2,…, we obtain respectively that:
The following step in this demonstration is different from the step proposed in other textbooks [2, 3]. The partial derivative of f with respect to (λy1) can be expressed as:
Considering that f is a homogeneous function of one degree with respect to the variables y1,y2,… and making Δ’= Δ/λ in (29),
The differential of f with respect to λ in the right side of (24) is:
Eq. (25) is obtained by substituting Eqs. (27), (28), (30), (31) in Eq. (26). In addition, it is interesting to see that, defining f1 as f1 = (∂f/∂x1) and using (30), f1 is a homogeneous function of zero degree with respect to the variables y1, y2,…:
Let it be a three-component system (e.g., as those of Figure 1A and C). Being J an extensive property, a description by components is:
where n1, n2 and n3 are the number of moles of components 1, 2 and 3. The partial property of 1 is defined as:
From the above section, we know that j1;2,3 is homogeneous function of zero degree with respect to n1, n2 and n3. With this and considering λ = 1/(n1+n2+n3),
where we have considered that x1 is a function of x2 and x3 because x1 = 1−x2−x3. From (35), we see that the partial molar properties depend only on the composition of the system. Alternatively to (35), we could use other scales of composition/concentration to express j1;2,3.
The equation of Gibbs is obtained by differentiating J in (33) and using Eq. (34) and similar definitions for components 2 and 3:
The Euler equation is obtained by considering that J is a homogeneous function with respect to n1, n2 and n3 and applying the Euler’s theorem:
The Gibbs-Duhem equation is obtained by differentiating in Eq. (37), equalling to Eq. (36) and cancelling common terms:
If we consider that partial molar properties are function of n1, n2 and n3, Eq. (38) would be the Gibbs-Duhem equation in the representation of variables n1, n2 and n3. The representation in the variables x2 and x3 is as follows. Dividing (38) by the total number of moles,
Calculating the differentials by considering that partial molar properties depend on x2 and x3, and bearing in mind that x2 and x3 are independent variables, (38) can be written in an alternative way as:
In a description by fractions, we consider the three-component system as composed of a component 1 and a group (or fraction) composed of components 2 and 3. Figure 1B shows the example when two solutes are grouped in a “complex solute”, and Figure 1D shows the example in which a polymeric particle composed of polar and non-polar groups is considered as a fraction of the system. In this case, the extensive property J is expressed as:
where
The variable nF is the total number of moles of the fraction F, and xf3 is a variable related to its internal composition. The partial molar properties of J in this description are:
Because J is a homogeneous function of n1 and nF, the partial properties j1;F and jF;1 will be homogeneous functions of zero degree with respect to the variables n1 and nF. In this way and similarly to Eq. (35):
where xF = nF/(n1+nF). Now, we will see the relation between both descriptions. From (42) and (43), the change of variable of Eq. (8) is in this case:
Substituting (47) in (13) and the result in (17), one obtains that:
The equations of Gibbs, Euler and Gibbs-Duhem in this description are as follows. The Gibbs equation is obtained by differentiating in (41) and considering the definitions given in (44) and (45):
The Euler equation is obtained by remembering that J is a homogeneous function of degree one of n1 and nF and using the Euler’s theorem:
The Gibbs-Duhem equation in the representation of variables xF and xf3 is obtained by differentiating in (52), equalling to (51) and cancelling common terms, and dividing by the total number of moles:
Considering that j1;F and jF;1 are functions of the independent variables xF and xf3, then (53) will take the form:
Calculating the partial derivative of jF;1 with respect to xf3 in Eq. (49) and substituting in Eq. (54), we obtain:
It is interesting to observe that considering constant composition (dxf3 = 0) in Eqs. (51)–(53), then the system behaves as a two-component system. This fact cannot be obtained using the description by components.
We consider intuitively a diluted solution when the properties of the solution are similar to those of its solvent in pure state. In this section, we will study the thermodynamic behaviour of the partial molar properties in this region of concentrations.
In this paragraph, we will define the concept of non-interaction and prove that when applying it to a system, the system behaves as an ideal mixing. From a thermodynamic point of view, the components of a system are not interacting if both following points hold simultaneously.
The state of each component in the system, expressed in terms of its partial molar properties, does not vary by changes of composition of the other components. It means each component does not detect the presence of the other components.
The formation of the system from its pure components is carried out with any cost of energy, neither for the system nor for the surroundings.
Mathematically, the first point can be written as:
Substituting (56) in (40) and considering also that:
it is obtained that:
Because j1;2,3 depends only on x1:
and then (57) yields:
Because the first term depends only on x1 and the second and third terms depend only on x2 and x3, respectively, from (60), we have that:
where kJ is a function, which only depends on temperature T and pressure P. Similar equations to (61) are obtained for j2;1,3 and j3;1,2. Integrating in (61) between
For components 2 and 3, similar equations to (62) are obtained. Now, we will apply the second point of the above definition of non-interaction. The zero cost of energy for the system and surroundings is equivalent to:
Considering u1; 2,3, h1; 2,3 and v1; 2,3 as (62) and bearing in mind (63):
In addition to this g1;2,3 (free energy of Gibbs),
Combining Eqs. (64)–(66), we have that:
where k is a constant. For the entropy, one gets:
With this,
and we have demonstrated that a system holding the non-interaction definition proposed is an ideal mixing.
In this section, we will define the thermodynamic concept of diluted solutions and study the behaviour of the partial molar properties of these solutions. Commonly and intuitively, we consider a solution as diluted when its properties are similar to those of the pure solvent. We can implement mathematically this concept in the following way. When we remove all solutes from a solution, we have that:
where j is the molar property of the extensive thermodynamic property J. In addition, the partial derivatives must vanish:
Otherwise, we would have memory effects and we can see this with an example. If we purify water, the pure substance obtained does not depend on the initial diluted solution employed. Actually, pure water is commonly used as a standard because it does not depend on the part of world, in which it is obtained. The Taylor’s expansion of j1;2,3 is:
where ∇j1;2,3(0,0) and Hj1;2,3(0,0) are, respectively, the vector gradient and the Hessian of j1;2,3 matrix at (0,0). Considering (71) and (72) in (73) and that all partial derivatives mush vanish at (0,0), we have that for diluted solutions:
From Eq. (74), we have for diluted solutions:
The behaviour of molar partial properties of solutes is as follows. Considering a “complex solute” S composed of 2 and 3 (as in Figure 1B),
and substituting Eq. (74) in the first equation of (55),
Inserting Eq. (76) in the second equation of (55), it is obtained that:
Until now, we have seen the effect of the dilution in the capacity of detecting the presence of other components in a diluted solution. In order to gain an insight into the interactions, we have to study the process of mixing in diluted solutions. From (71), we can write:
It indicates that in the limit of infinite dilution, components do not interact because the process of mixture does not have any energy cost. This result implicates that in diluted solutions, according to the asymptotic approach given by Eq. (74), the interaction between solvent and solutes is weak and it can be neglected.
The molar property j of a diluted solution can be written as:
where we are considering the interaction between components 2 and 3 since
In a diluted solution without interaction between 2 and 3, the property jØ can be written as:
In this way, we can calculate the interaction contributions to j as:
where
is the partial molar property of interaction of the complex solute and
are the partial molar properties of interaction of the components 2 and 3, respectively. These properties are not independent as we will see as follows. Combining (78) and (85),
In Eq. (85), Δj2;1,3 and Δj3;1,2 are evaluated when using concentrations xS and xs3. Accordingly, j2,1 is evaluated using the concentration x2 given by x2 = xS (1−xs3), and then,
Considering the Gibbs-Duhem equation for a two-component system:
in Eq. (87) and bearing in mind that solutions are diluted,
Similarly for component 3,
Substituting (89) and (90) in (86), we obtain:
Eq. (91) indicates that in a diluted solution, the interaction between components 2 and 3 is not vanished. The partial molar property of interaction of the complex solute can be calculated experimentally as:
and the partial properties of interaction of components 2 and 3 can be obtained from (92) using the equations:
Eq. (93) is obtained by differentiating in Eq. (92) with respect to xs3, using Eq. (91) and combining the result with Eq. (92). As we will see below, Eq. (93) will allow us to obtain the interaction partial properties of 2 and 3 from experimental data.
As an example, we will consider the interaction between functionalized polymeric particles and an electrolyte at 30°C [4]. For that, polymeric particles synthesized of poly(n-butyl acrylate-co-methyl methacrylate) functionalized with different concentrations of acrylic acid were used in this study. The electrolyte was NaOH. Similarly to Figure 1A, water (solvent) was considered as component 1, polymeric particles as component 2 and electrolyte as component 3. And similarly to Figure 1B, the system was fractionalized in component 1 and a complex solute composed of polymeric particles and electrolyte. The experimental measurements were carried out using a Density and Sound Analyzer DSA 5000 from Anton-Paar connected to a titration cell. It is of full cell type, which is usually employed in isothermal titration calorimetry. Polymeric particles were located in the titration cell, and electrolyte was located in the syringe. Concentrations of polymeric particles (c2) and electrolyte (c3) after each titration were calculated as [4, 5]:
where V is the effective volume of the titration cell, v is the titration volume and
(A) Density as function of the electrolyte concentration c3 (g/L). (B) Sound speed as function of the electrolyte concentration. (C) Partial specific volume of the complex solute composed of polymeric particles and electrolyte as function of the mass fraction of the electrolyte in the complex solute (ts3). (D) Partial specific adiabatic compressibility of the complex solute as function of tf3.
Considering the solution in the cell as diluted, the partial specific volume (and similarly the partial specific adiabatic compressibility) of the complex solute can be calculated as:
where t1 and tS are the mass fraction of the water and of the complex solute, respectively. Figure 3C and D shows the partial specific volume and partial specific adiabatic compressibility as function of tf3 (mass fraction of the electrolyte in the complex solute). The term of interaction ΔvS;1 is calculated by Eq. (92), where v2;1 is obtained by considering that:
in Figure 3C. The term v3;1 is calculated by extrapolating the linear part of vS;1 in Figure 3C as:
The partial specific volume of interaction of the polymeric particles (Δv2;1,3) and the partial specific volume of interaction of the electrolyte (Δv3;1,2) were obtained using Eq. (93). The numerical method employed to calculate the derivatives is shown elsewhere [4]. Figure 4 shows the values of ΔvS;1, Δv2;1,3 and Δv3;1,2, and Figure 5 shows the values of Δks S;1, Δks 2;1,3 and Δks 3;1,2 obtained in a similar way than for volumes.
(A) Partial specific volume of interaction of the complex solute (polymeric particles + electrolyte) as function of the mass fraction of the electrolyte in the complex solute (ts3). (B) Partial specific volume of interaction of the polymeric particles as function of ts3. (C) Partial specific volume of interaction of the electrolyte as function of ts3.
Partial volume of polymeric particles (v2;1) can be broken down in the following contributions [6–11]:
which are shown in Figure 6. The atomic volume contribution (v2;1/atom) is the sum of all volumes of the atoms, which make up polymeric chains. The free volume contribution (v2;1/free) is consequence of the imperfect packing of the polymeric chains. The atomic volume contribution and free volume contribution are both positive contributions. The hydration contribution (v2;1/hyd) is negative, as a consequence of that the specific volume of water molecules in bulk is larger than the specific volume in the hydration shell. The contributions to the partial specific adiabatic compressibility are the free volume and hydration because the effect of the pressure on the atomic volume is neglected [10, 12–21]:
(A) Partial specific adiabatic compressibility of interaction of the complex solute (polymeric particles + electrolyte) as function of the mass fraction of the electrolyte in the complex solute (ts3). (B) Partial specific adiabatic compressibility of interaction of the polymeric particles as function of ts3. (C) Partial specific adiabatic compressibility of interaction of the electrolyte as function of ts3.
Contributions to the partial volume in a polymeric particle.
The contribution kT 2;1/free is positive, and the contribution kT 2;1/hyd is negative [4, 8]. In this chapter, we will take the adiabatic compressibility as an approximation of the isothermal compressibility. For the electrolyte, the free volume contribution is null, and then, v3;1 and kT 3;1 will take the following form:
For the complex solute, we can write a similar breakdown:
Inserting Eqs. (100), (102) and (104) in Eq. (92) and neglecting the variation in the atomic contributions, the following equation for the interaction specific partial volume is obtained:
where
Substituting (105) in (93), we get
Defining now:
One arrives at the following result:
where similar equations are obtained for the interaction partial specific compressibilities.
Considering these contributions, the interpretation of the partial specific volumes of interaction of the particle as function of the electrolyte concentration is as follows. From tf3 = 0 to around 0.05 (see Figure 4B), there is an increment in Δv2,1,3 which can be interpreted as a gain of free volume by the disentanglement of the polymeric chains. This increment of free volume is accompanied by an increment in the hydrodynamic radius [4]. From around tf3 = 0.05 to around 0.1, there is a decrement in Δv2,1,3 due to hydration. In this region of compositions, the separation of polymeric chains allows the entrance of water molecules in the polymeric particle. As a result, the hydrodynamic radius of the particle increases [4]. From around ts3 = 0.1 to 0.15, Δv2,1,3 increases sharply. This fact can be interpreted as an increment of the dehydration. Beyond ts3 = 0.15, Δv2,1,3 becomes constant, indicating that the interaction between particles and the electrolyte is saturated. Similar regions with similar interpretations are obtained for the partial specific adiabatic compressibility (see Figure 5B).
This section deals with the determination of the partial specific enthalpies of interaction of the same system than in the latest example [4]. Partial specific enthalpy of interaction of polymeric particles is:
and the partial specific enthalpy interaction of the electrolyte is:
The partial specific enthalpy of interaction of the electrolyte can be measured by isothermal titration calorimetry using the combination of two experiments [6, 7]. The first experiment is locating the polymeric particles in the cell and the electrolyte in the syringe. The heat per unit of titration volume in an infinitesimal titration is:
where ρs is the density of the stock solution and
The partial specific enthalpy of interaction of the electrolyte is obtained by subtracting (114) from (113), considering Eq. (112), diluted solutions and bearing in mind that
Figure 7A shows the experimental values Δh3;1,2. The partial specific enthalpy of interaction of polymeric particles was calculated by integrating Eq. (91) [7]:
(A) Partial specific enthalpy of interaction of the electrolyte as function of the mass fraction of the electrolyte in the complex solute (ts3). (B) Partial specific enthalpy of interaction of the polymeric particles as function of ts3.
and the values of Δh2;1,3 are shown in Figure 7B. It is very interesting to observe in Figure 7B that Δh2;1,3 is zero from ts3 = 0 to around ts3 = 0.1. This fact indicates that the changes, which take place in the first two regions in Figures 4B and 5B, are entropic in origin.
First, we will discuss the case of the two-component system and then make the extension to three-component system. In this section, J can be U, H, V or their derivatives Cv = (∂H/∂T)V, Cp = (∂H/∂T)P or E = (∂V/∂T)P, KT = (∂V/∂P)T and KS = (∂V/∂P)S.
In a two-component system, we only have one way to calculate limits at infinite dilution and it is to take a component as solvent (component 1) and the other as solute (component 2). For a two-component system, j takes the form:
Because
and using Eq. (117), we have:
For the solute, we have:
We can obtain experimentally the value of
Differentiating (117) with respect to x2, considering the Gibbs-Duhem equation for a two-component system, Eq. (117) again and Eq. (120) in (121):
For this reason, we can obtain experimentally
In three-component systems, we have two ways to calculate limits at infinite dilution. The first way is to group two components in a “complex solvent” and to calculate the limit at infinite dilution of the other component in this complex solvent (type I). The other way is considering a component as solvent, to group the other two components in a complex solute, and to calculate the limit at infinite dilution of the complex solute in the solvent (type II).
In this case, we consider a complex solvent B composed of components 1 and 2 and a solute (component 3). For this system,
where nB = n1+n2 and xb2 = n2/(n1+n2). With this, j can be written as:
where x3 is the mole fraction of the component 3. At infinite dilution, we have:
and then combining Eq. (124) with (125), one gets for the solvent:
For the solute, it is obtained that:
where we have used Eq. (48). Similar to the case of two-component systems, the amount
This equation is obtained by using the first-order Taylor’s expansion of j(x3,xb2) around x3 = 0, the partial derivative of j(x3, xb2) with respect to x3, the Gibbs-Duhem equation of the fractionalized system considering the composition of the fraction as constant and Eqs. (126) and (127).
In this case (see Figure 1A and B), we will consider the component 1 as solvent and a “complex solute” S composed of 2 and 3 and then:
where nS = n2+n3 and xs3 = n3/(n2 + n3). The molar property j is:
Similarly to the above cases, at infinite dilution we have for the solvent:
Accordingly to case of the two-component system, one gets for the complex solute:
and in a similar way than for the type I limits,
In order to study the contributions of components 2 and 3 to
In this way, taking limits in both sides of Eq. (49), and bearing in mind Eqs. (132) and (134), we have that:
Now, we will see some mathematical properties of limits of type II. One of them is for example:
This property is demonstrated by using iterated limits:
The other mathematical property is:
where its demonstration is as follows:
Now, it is necessary to consider other way to fractionalize the system. For convenience, we will consider a complex solvent B composed of 1 and 3, and a solute 2 where the variable xB represents the molar fraction of B and xb3 = n3/(n1+n3). With this,
and considering Eq. (140), (139) transforms into:
Other interesting property of the limits of type II is that they are related to each other by the following equation:
The demonstration of this equation is as follows. Both sides of the following equation:
are calculated in the following way. The left-hand side is obtained by deriving partially Eq. (49) with respect to xs3. The right-hand side of (143) is calculated considering that:
Using (50) in (144) and cancelling common terms, Eq. (143) is obtained. Taking the limit when xs approaches to zero when xs3 is kept constant in both sides of Eq. (143) and considering that:
Eq. (142) is obtained.
From values of
Eq. (146) was obtained by differentiating Eq. (135) with respect to xs3, considering Eq. (142) and combining the result with Eq. (135).
The polymeric particles used were synthesized with a gradient of concentration of functional groups (acrylic acid) inside the particle [9]. In this system, the content of acrylic acid represents the polar groups, while poly(butyl acrylate-co-methylmethacrylate) is the non-polar groups. As seen in Figure 1C and D, component 1 is water, component 2 is non-polar groups and component 3 is polar groups. The polymeric particle (composed of polar and non-polar groups) is taken as a fraction “P” of the system where the variable tp3 = n3/(n2+n3) will be the mass fraction of polar groups in the particle. In this study [9], the same experimental equipment than in Section 4.4.1 was used and measurements of density and sound speed were carried out by titrating water (in the cell) with latex of polymeric particles (in the syringe). Figure 7A and B shows the density ρ and u as functions of the concentration for several values of tp3. The density and sound speed were transformed into specific volumes and specific adiabatic compressibilities by using Eqs. (95) and (96), and results are shown in Figure 1C and D.
In this case, Eq. (133) will take the form:
and considering that t1 = 1 – tP, Eq. (147) transforms into:
Using Eq. (148) as a fit function in Figure 8C and D, the partial specific volume at infinite dilution of the particles (
(A) Density of latex as function of polymeric particles concentration. (B) Sound speed as function of polymeric particles concentration. (C) Specific volume of latex as function of mass fraction of solvent (water). (D) Specific adiabatic compressibility as function of the mass fraction of solvent (water). In all figures (□) 0 wt%, (○) 5wt%, (∆) 10 wt%, (◊) 15 wt%, (◃) 20 wt%, (⬢) 25wt%.
(A) Partial specific volume of the polymeric particles at infinite dilution as function of the polar group content. (B) Partial specific adiabatic compressibility of particles at infinite dilution as function of the polar group content. (C) Partial specific volume of non-polar groups at infinite dilution as function of the polar group content. (D) Partial specific adiabatic compressibility of non-polar groups at infinite dilution as function of the polar group content. (E) Partial specific volume of polar groups at infinite dilution as function of the polar group content. (F) Partial specific adiabatic compressibility of polar groups at infinite dilution as function of the polar group content.
The partial specific properties of polar (
With similar arguments than in Section 4.4.1, we can get the following equations for the volumes:
and for the adiabatic compressibilities:
In addition to this, by combining Eqs. (135), (149), (151) and (152), one gets the following equations:
where similar equations can be obtained for the adiabatic compressibilities. Figure 9A and B shows that
In this chapter, we have developed common thermodynamic bases for isothermal titration calorimetry, densimetry and measurement of sound speed in terms of thermodynamic partial properties (interaction partial enthalpies, partial volumes and partial adiabatic compressibilities). To build these common thermodynamic bases, it is necessary to introduce new concepts, i.e., the concept of fraction of a system and the concept of thermodynamic interaction between components of a system. An advantage of the proposed thermodynamic scheme is the possibility of including new thermodynamic partial properties as partial heat capacities.
Fruits and vegetables are appreciated as “healthy foods” compared with beef or pork meat. Many epidemiological studies as well as clinical investigations have suggested that a vegetable-based diet is beneficial in preventing chronic diseases including cancer, coronary heart disease, stroke and hypertension [1, 2]. Meanwhile, traditional herbal medicines have used specific plant species that contain phytochemicals exhibiting pharmacological activities [3]. Novel compounds have been isolated from such plants and they have been chemically synthesized for pharmaceutical production [4]. Nobody doubts that edible plants are beneficial in human health.
\nIn “western” medicine, a disease can be defined as dysfunction of a physiological mechanism. Based on this concept, a drug in general is presumed to act on a specific component of a physiological mechanism. In many cases, these are inhibitors of enzymes or transporters, showing the “one-to-one” relationship between drug and target molecule. While recent drug designs have drastically changed due to a rapid development of computer technology [5] as well as gene therapy [6], the hunt for novel bioactive compounds contained in plants is still active for new drug discovery.
\nThe “one-to-one” philosophy in medicine and pharmacology works well, if the cause of a disease is ascribed to a single component such as a protein or an enzyme. However, most diseases that are difficult to prevent and cure are “syndromes” that are governed by multiple components with complicated interactions. Whatever the cause of such diseases, overproduction of harmful reactive oxygen species (ROS) can often be observed in progression of the disease. Under such conditions, the cells may be challenged by “oxidative stress” due to excessively generated oxidants. The oxidative stress potentially impairs cellular functions eventually leading to death [7, 8]. This is a common biological feature that can be seen in all living organisms including bacteria, fungi, plants and animals. Living organisms have evolved to cope with the oxidative stress induced by biotic (pathogen attack or biological interactions) and abiotic (or environmental) stresses. Thus, under stress conditions, living organisms need to control cellular ROS levels for their survival. In this context, antioxidant systems are essential in any living organisms. This is a biological rationale for the importance of antioxidants in prevention and cure of diseases in humans.
\nPlant antioxidant research shows a history of twists and turns. Some early studies had suggested concepts opposite to the present recognition. Plant antioxidants had sometimes even been considered to be toxic or carcinogenic to animals. Contradictory reports in the old literatures may lead non-specialists to a state of confusion. Thus, to follow the current state of research advances in phytochemical antioxidants, understanding its historical background is of help for non-specialists and new researchers. Highlighting the research progress of plant pigments flavonoids and betalains, here, we provide an overview of phytochemical antioxidants with some prospects for future research.
\nA retrospective of the history of research on plant antioxidants needs to go back to the age of discovery. When voyagers such as Magellan, Columbus, Vasco da Gam and Cook were sailing over the world’s oceans, more than three times as many sailors died due to the mysterious disease “scurvy” as soldiers died in the American Civil War [9]. For hundreds of years, the cause of the disease had not been clarified and there had been no cure for this disease of sailors [10]. In 1747, James Lind working as a naval surgeon at sea on the HMS Salisbury conducted “clinical trials” of potential cures for the disorder. In Treatise of the Scurvy published in 1753, he reported that there was no effect with the potential remedies vinegar, mustard, garlic purges, elixir of vitriol, but citrus fruits (orange and lemon) showed a significant cure effect [11]. It is now known that scurvy is caused by a vitamin C (L-ascorbate) deficiency due to a lack of fresh fruits and vegetables.
\nHistorically, antioxidant and vitamin studies have developed independently in chemistry and health science, respectively. In chemistry, antioxidants were defined as chemical compounds that can suppress oxidation reactions. In early studies, oxidation was observed as absorption of molecular oxygen in a reaction such as polymerization reaction of natural rubber. On the other hand, a vitamin (the name “vitamine, vital + amine” was the original proposal and it was later renamed to “vitamin”) was defined as an organic nutrient that is essential for human health care. The major recognized vitamins are vitamin A, B1, B2, B3, B5, B6, B7, B9, B12, C, D, E, and K. The biochemical requirements of these vitamins were revealed after their chemical identifications. Among these vitamins, vitamin A, C and E have been highlighted again in the late 20th century due to their antioxidant activities that potentially reduce the oxygen toxicity.
\nAlthough molecular oxygen (O2) is required for respiration in animals, a high concentration or high partial pressure of oxygen often damages the central nervous and pulmonary systems, which leads to disease or death. Oxygen toxicity in the central nervous system and that in pulmonary system had been referred to as the Paul Bert effect and the Lorrain Smith effect, respectively [12]. Although the toxicity of oxygen itself was implied by Joseph Priestley in 1774 (dephlogisticated air at that time) [13], the modern style of experimental science has been opened up by Bert (1833–1886), the Father of Aviation of Medicine [14, 15]. In his La Pression Barometrique (1878), Bert described that a high partial pressure of breathing oxygen (hyperoxia) can lead to death of animals, the first experimental demonstration for the toxicity of pure oxygen [14]. Since his pioneering discovery had not been appreciated for a long time, unfortunately, eye damage (retinopathy of prematurity) to premature infants frequently occurred due to the use of pure oxygen [16].
\nThe biochemical basis of the oxygen toxicity is ascribed to overproduction of reactive oxygen species (ROS) in cells. The ROS firstly produced in cells is mostly superoxide radical (O2\n−), which is the reaction product of the one electron reduction of molecular oxygen (O2) [17]. Whereas chemists have known the inorganic reaction that produces O2\n− from O2, the biological relevance of the reaction had not been considered in biochemistry. At that time most biochemists were fascinated by the oxidative phosphorylation that is the final step of ATP synthesis in aerobic respiration. For mitochondrial ATP synthesis, the presence of O2 is prerequisite to drive the respiratory electron transport. Therefore, the toxicity of O2 had been overlooked. The discovery of the enzyme superoxide dismutase (SOD) that destroys O2\n− is a landmark in the research history of oxygen toxicity [18]. The discovery of the antioxidant enzyme SOD has drastically changed our recognition: O2 might be toxic for living organisms.
\nTo prevent oxygen toxicity, it has been revealed that antioxidant enzyme systems are essential for the survival of all living organisms, including humans. The ROS O2\n− and H2O2 can be removed by the enzymatic reactions of SOD and peroxidases, but other unstable ROS molecules, hydroxyl radicals (•OH) for example, cannot be destroyed by those enzymatic reactions. These molecules are scavenged by antioxidants. Vitamin A or carotenoid can scavenge singlet oxygen (1O2) that could be produced in the eyes or skin under ultraviolet (UV) light [19]. Vitamin E, or 𝛼- tocopherol, can react with the ROS radicals produced in lipophilic environments such as in lipid membranes. Vitamin C (ascorbate) serves as a universal reducing power to the antioxidant enzyme systems while the ascorbate molecule itself scavenges various types of ROS (except H2O2) by its spontaneous reactions [20]. It is important to note that humans need to acquire these essential antioxidant vitamins (A, C, E) from dietary foods, largely from fruits and vegetables.
\nHistorically, there was a short-lived Vitamin P concept. Albert Szent-Györgyi, a Nobel prize winner who isolated ascorbate, demonstrated that flavonoid glycosides rich in citrus fruits can behave similar to ascorbate in maintaining capillary permeability [21]. Based on his observations, Szent-Györgyi proposed that the plant flavonoids, as a group of plant pigments, are also essential nutrients and referred to them as vitamin P (permeability) [22]. However, this vitamin P concept did not gain broad acceptance due to the chemical diversity of flavonoids. More recently, his idea that flavonoids can complement the function of ascorbate has been renewed with the development of the antioxidant hypothesis.
\nPlant fruits and flowers display beautiful colorations ranging from blue to red. These plant colorations are produced with three major pigments i.e., chlorophylls, carotenoids and flavonoids. In plants, biological functions of chlorophylls and carotenoids have been known as the photosynthetic pigments that absorb light energy to drive photosynthesis. In contrast, only the visual attraction for flower pollinators such as bees or butterflies had been proposed as a biological function of colored flavonoids for a long time [23]. The chemical diversity of flavonoids found across plant species had made it difficult to consider common physiological or biochemical functions. Conversely, the huge chemical diversity of flavonoids was useful for plant taxonomy until amino acid or DNA sequence information available.
\nIn 1990s, red anthocyanin, a flavonoid subgroup, was highlighted to account for the paradoxical epidemiological observation termed the “French paradox”. French people have a relatively low incidence of coronary heart disease even though they consume a diet relatively rich in saturated fats [24]. Researchers were interested in anthocyanins and polyphenols contained in red wine that may suppress heart disease through their antioxidant activities [24]. Similarly, the longevity of Japanese people was explained by their daily consumption of green tea rich in catechin, another subgroup of flavonoid [25, 26]. These epidemiological reports have stimulated biochemical screening of natural antioxidants contained in plants.
\nTo date, health science, biochemistry, botany and other different field of studies have been integrated into antioxidant research. A timeline for antioxidant research of phytochemicals is summarized in Figure 1.
\nA timeline of antioxidant research of phytochemicals. Flavonoids are major plant pigments that are widely appreciated as natural antioxidants. Historically, antioxidant studies, vitamin studies and flavonoid studies have independently progressed in health science, biochemistry and botany, respectively. These different lines of studies have been integrated into the present plant antioxidant studies.
Flavonoids are representative secondary metabolites of land plants. The pigments commonly accumulate in epidermal cells of the organs such as in flowers, leaves, stems, roots, seeds and fruits [27, 28]. Flavonoids are found as glycosidic forms (glycosides) and non-glycosidic forms (aglycones). Subcellular localization of the glycosides is largely confined to hydrophilic regions such as vacuoles and apoplasts. The aglycones are localized in lipophilic regions e.g., oil glands and waxy layers.
\nThe term “flavonoid” originated from its yellow color (the Latin word flavus means yellow). Bioactive flavonoids such as flavones and flavonols are sometimes referred as to “bioflavonoids”. Figure 2 shows the basic structures of flavonoids. The general structure of flavonoids includes a C6-C3-C6 carbon skeleton with two phenyl rings (A- and B-rings) and a heterocyclic ring (C-ring). Based on the structure of the aglycones, flavonoids can be classified into subgroups: chalcone, flavanone, flavone, isoflavone, flavonol, and anthocyanidin (Figure 3). According to the IUPAC nomenclature, flavonoids are recommended to be subcategorized into flavonoids (bioflavonoids), isoflavonoids and neoflavonoids [29]. Since this classification has yet not been widely adopted, in this chapter, traditional phytochemical names and classifications are used to avoid confusions. Most of these subgroups show yellowish coloration while anthocyanins exhibit multiple colorations depending on the aglycone structure, the presence of metal, pH and conjugation with other molecules (Figure 3).
\nChemical structures of flavonoids. Chemical structures of flavonoids include a C6-C3-C6 carbon skeleton with two phenyl rings (A- and B-rings) and a heterocyclic ring (C-ring). Left, the basic structures of a flavone, isoflavone and flavonol. Right, the basic structures of anthocyanin. The –R on the rings can be replaced by other molecules including sugars to make a huge variety of chemical structures of flavonoids.
Representative flavonoid subgroups. Based on the aglycone structures, flavonoids can be classified into flavone, isoflacone, flavonol, chalcone and anthocyanidin. Representative flavonoids with parenthesis along with apparent visual colorations are shown.
Common glycosylation positions are the 7-hydroxyl in flavones, isoflavones and dihydroflavones; the 3- and 7- hydroxyl in flavonols and dihydroflavones; the 3- and 5-hydroxyl in anthocyanidins [30]. The typical sugars involved in glycoside formation are glucose, galactose, rhamnose, xylose and arabinose. In addition to the glycosylation, methylation, isoprenylation and dimerization occur at those positions [30]. These modifications produce a huge structural diversity of flavonoids. More than 9,000 chemical structures of flavonoids have been reported to date [31].
\nEnzymes and genes involved in flavonoid biosynthesis have been identified [27, 32, 33, 34, 35]. Figure 4 shows an outline of biosynthetic pathways of the major subclasses of flavonoids. Flavonoids are synthesized from phenylalanine, an aromatic amino acid produced in the shikimate pathway. Phenylalanine is sequentially metabolized by phenylalanine ammonia-lyase (PAL), cinnamate 4-hydroxylase, and 4-coumarate CoA ligase to 4-coumaroyl CoA. This 4-coumaroyl CoA and 3 molecules of malonyl CoA are condensed by chalcone synthase to form the flavonoid chalcone (yellow). Chalcone is isomerized to the flavanone naringenin (colorless) by chalcone isomerase. Naringenin is further converted to flavones (pale yellow) and isoflavone (pale yellow) catalyzed by flavone synthase and isoflavone synthase, respectively. Naringenin is hydroxylated to dihydroflavonol by flavanone 3-hydroxylase and further metabolized to flavonol (yellow) by flavonoid synthetase. Dihydroflavonol is converted to anthocyanidin (red, red-violet or blue-violet), an aglycone of anthocyanin, by dihydroflavonol 4-reductase and anthocyanidin synthase. Anthocyanidin is glycosylated by UDP-glycose-dependent glycosyltransferase. Manipulation of those genes has been challenged to change of flower or fruits coloration [28].
\nAn outline of flavonoid biosynthesis pathways in plants. The synthesis of the flower pigment anthocyanins requires multiple steps including the shikimate pathway, phenylpropanoid pathway, via chalone and flavanone. The number of required enzymatic steps reflects the evolutional order of the pigments.
Antioxidant activity or antioxidant capacity of flavonoids has been experimentally evaluated with either assays based on hydrogen atom transfer (HAT) reaction or assays based on electron transfer [36]. There are several protocols or assays that have been proposed. The ORAC (oxygen radical absorbance capacity), TRAP (total radical trapping antioxidant parameter) and crocin bleaching assays are based on HAT. TEAC (Torolox equivalent antioxidant capacity), ABTS (2,2′-azino-bis-(3-ethyl-benzthiazoline-6-sulfonic acid)) and DPPH (1,1-diphenyl-2-picryl-hydrazyl) assays are based on the electron transfer activity. Among these protocols, the DPPH assay has been widely used for plant materials because it is an easy and accurate method suitable for measuring antioxidant activity of fruits, vegetable juices or plant extracts [36]. Inhibition of the lipid peroxidation reaction is also a measure to assess the antioxidant activity of plant polyphenols [37].
\nIn addition to the reactions with model radical substrates, it has been demonstrated that flavonoids can directly react with a various type of ROS. The flavonol quercetin was demonstrated to show quenching activity for the singlet oxygen (1O2), a non-radical ROS molecule [38]. The flavonol kaempferol [39] and the anthocyanidin cyanidin [40] in vitro were shown to scavenge superoxide radical (O2\n−). The flavonol quercetin was reported to scavenge hydroxyl radicals (•OH) produced by radiolysis of water [41, 42]. The flavonols rutin and quercetin were demonstrated to scavenge the hydroperoxide of linoleic acid (LOO•) to inhibit lipid peroxidation [43]. It is now evident that flavonoids are natural plant antioxidants contained in fruits and vegetables.
\nIn principle, the OH groups on the aromatic rings of flavonoids are responsible for the antioxidant or free radical scavenging activity. Most antioxidant flavonoids share the catechol structure with two hydroxy groups (-OH) and/or the double bond between C2-C3 and carbonyl structure [44, 45]. Antioxidant flavonoids satisfying such criteria bear multiple hydroxy groups in a molecule, thereby the name of “polyphenols” being synonymously used for plant antioxidants by the public. It should be noted that polyphenol structure can be found not only in flavonoids but also in other plant phenolic compounds such as hydroxycinnamic acid [35].
\nWhen polyphenols scavenge ROS, either through a direct chemical reaction or as an electron donor for an enzymatic reaction, polyphenolic compounds are oxidized and phenoxyl radicals are generated [46]. The phenoxyl radicals are unstable, forming dimers or polymers as a result of spontaneous reaction. Tannin and lignin are the polymerization products of such phenoxyl radical reactions. In the presence of reductant such as ascorbate, the phenoxyl radicals produced are rapidly regenerated into their parent compounds [46]. The enzyme monodehydroascorbate reductase (MDAR) was demonstrated to regenerate flavonoids from their phenoxyl radicals, a possible recycling system of antioxidants [47]. In plants, it has been proposed that flavonoids complement the ascorbate antioxidant system [35].
\nPlant coloration can be mostly attributed to spectral property of the colored flavonoids, i.e., anthocyanidins. The plant pigment betalains are exceptional. The term “betalain” comes from the Latin name of the common beet (Beta vulgaris) from which betalains were first extracted. Betalains are a class of tyrosine-derived pigments that are distributed in only 13 families of Caryophyllales order such as red beet (Amaranthaceae) and cactus (Cactaceae), and in some fungi [48], where they replace anthocyanin pigments [32]. To date, anthocyanins and betalains have never been detected jointly in plant tissues [48]. The biological meaning of the mutually exclusive relationship between betalains and anthocyanidins is still unknown [49, 50].
\nBetalains are immonium derivatives of betalamic acid [4-(2-oxoethylidene)-1,2,3,4-tetrahydropyridine-2,6-dicarboxylic acid] [48]. Betalains are classified into two groups: betacyanin (red-violet) and betaxanthin (yellow) as shown in Figure 5. Betacyanin is a conjugate with cyclo-dopa and its glycoside, while betaxanthin is a conjugate with amino acid or amine (Figure 5).
\nStructures and biosynthesis pathways of betalains. Betalains are synthesized from L-tyrosine via L-dopa. The intermediate betalamic acid is condensed with cyclo-dopa glycoside or amino acid/amine to betacyanin and betaxanthin, respectively.
In contrast with flavonoids, biosynthetic pathway of betalains in plants has not been fully clarified [32, 50, 51]. Hydroxylation of tyrosine by tyrosinase or polyphenol oxidase produces L-dopa, which is catalyzed by 4,5-dopa dioxygenase to form betalamic acid, the basic common skeleton of betalains. Cyclo-dopa, a component of betacyanin, had been considered to be formed by spontaneous chemical reaction after L-dopa is oxidized to dopaquinone by tyrosinase. Recently, the cytochrome P450 CYP76AD1 has been identified as the enzyme which catalyzes the conversion of L-dopa to cyclo-dopa, a novel biosynthesis route [52]. CYP76AD1 is a bifunctional enzyme that catalyzes tyrosine hydroxylation as well as cyclo-dopa synthesis. This P450 enzyme appears to play important roles not only in betacyanin synthesis but also in betalain synthesis. Furthermore, CYP76AD6 that catalyzes only tyrosine hydroxylation has also been reported [53]. No enzyme for condensing the obtained betalamic acid with a cyclo-dopa or an amino acid/amine has been found to date; instead, these condensations likely occur by a spontaneous reaction to form betacyanin or betaxanthin, respectively. Betacyanin usually accumulates as a glycoside, and two routes are estimated for glycosylation: cyclo-dopa being condensed with betalamic acid after it is glycosylated and cyclo-dopa and betalamic acid being condensed to be betacyanin and then glycosylated. Both are catalyzed by glucosyltransferases [54].
\nSimilar to flavonoids, betalains exhibit antioxidant or radical scavenging activity [55, 56]. In contrast with flavonoids, however, the chemistry of the antioxidant mechanism of betalains is less understood. It has been suggested that the common skeleton betalamic acid may contribute to their antioxidant activities [57, 58, 59]. Phenolic hydroxy group in cyclo-dopa moiety of betacyanin and the amino acid/amine portion of betaxanthin may increase the radical scavenging activities of betalamic acids [58]. Betalains can act as an electron donor for the enzyme peroxidases to detoxify hydrogen peroxide (H2O2) [60]. In food chemistry it has been suggested that the degradation of betalains during storage is suppressed in the presence of ascorbate, suggesting that betalain radicals formed by the oxidation might be reduced by ascorbate back to the parent molecules, similar to flavonoids.
\nIt is now evident that plant antioxidants remove ROS and free radicals that increase under oxidative stress conditions within cells. In addition to ROS, new players behaving similar to ROS have recently been identified, namely, reactive nitrogen species (RNS) and reactive sulfur species (RSS) [61]. As ROS refers to a group of reactive molecular species originating from molecular oxygen (O2), RNS and RSS are named for the groups of reactive molecular species derived from nitric oxide (NO) and hydrogen sulfide (H2S), respectively. Both NO and H2S are simple gaseous molecules that had initially been appreciated within the life sciences only for their toxicity [62]. Recent investigations have confirmed that NO and H2S are essential biomolecules synthesized in plants and animals. RNS and RSS are involved in the regulation of a variety of physiological processes. Along with carbon monoxide (CO), NO and H2S are categorized as “gasotransmitters” [62]. Until recently, many enzymes that produce NO and H2S have been identified in plants, animals and bacteria.
\nIt is important to note that NO and H2S are involved not only in physiological regulations (positive effect) but also in dysfunctions or disorders (negative effect). Similar to ROS, unregulated RNS and/or RSS production potentially causes dysfunction of metabolism under biotic as well as abiotic stress conditions, leading to sickness or death in humans [17]. Although a limited number of studies are available on anti-RNS and anti-RSS functions of phytochemicals, it has been reported that flavonoids and betalains could remove RNS and possibly RSS too.
\nNO reacts rapidly with O2\n− to produce the RNS peroxynitrite (ONOO−) following the reaction:
\nONOO− at physiological pH is unstable and is in rapid equilibrium with its conjugate acid, peroxynitrous acid (ONOOH, pKa\n 6.8) [63]. In early studies, NO was considered to act as an antioxidant because NO removes O2\n− from a solution as the consequence of the spontaneous reaction. However, this is half-side of a coin since the reaction product ONOO− attacks proteins and nucleic acids. The nitrated amino acid 3-nitrotyrosine (3-NO2-Tyr) is produced when ONOO− reacts with tyrosine residues of proteins, which potentially disturbs enzyme activities that may lead dysfunction of metabolism, a situation referred as to “nitrosative stress” [64]. It is now widely accepted that ONOO− is a major cytotoxic agent of RNS.
\nH2S is synthesized in plants and animals by multiple enzyme systems [62]. Biogenic H2S production is involved in various physiological mechanisms as a signaling molecule [62]. Analogous to ROS and RNS, H2S (or HS−) produces many reactive molecular species such as persulfide, polysulfide, polysulfane and others [65]. These RSS modify thiol (-SH) groups of the cysteine residue of proteins and change enzymatic activities, resulting in both positive regulation and negative inhibition. Uncontrolled overproduction of RSS is a potential risk to damage the cells. Although there is yet little evidence to confirm that flavonoids and betalains scavenge RSS, results of epidemiological studies imply that dietary phytoantioxidants also contribute to reduce the cytotoxicity of RSS in humans [66].
\nPlant phenolic compounds, such as anthocyanin [67, 68] and p-hydroxybenzoic acid [69], have been reported to scavenge ONOO− [70]. Betalains also react with ONOO− [71, 72]. As the consequence of these reactions, the phytochemical antioxidants inhibit the ONOO−-induced L-tyrosine nitration and DNA damage [35, 71]. In flavonoids, -OH group at the C3 position of the C-ring has been proposed to be involved in the ONOO− scavenging activity [69, 73]. As the result of the reaction with ONOO−, the phytochemical antioxidants are nitrated [74]. These in vitro studies have suggested that flavonoids and betalains potentially protect the cells from the nitrosative stress that may induce disorders or mutations [75, 76].
\nReactions of the phytochemicals that contribute to reduce the toxicity of RSS are largely unknown. The plant phenolic hydroxycinnamic acids are known to be sulfated by sulfotransferases highly expressed in the human liver and intestine [66]. Flavonoids act as inhibitors of the human sulfotransferases (SULTs) [66]. In plants, sulfate esters of flavonoids are rare compounds [77, 78] that are found in species occurring coastal and swampy areas as well as arid habitats [78]. Functions of sulfated flavonoids in plants and animals are not clear [79]. Sulfated flavonoids, such as quercetin 3-sulfate or quercetin persulfate, have been demonstrated with animals to show antioxidant activity, anti-inflammatory activity, antitumor activity and anticoagulant activity [80, 81, 82, 83]. These different lines of studies may imply that sulfated phytochemicals might be associated with physiological regulations in stress tolerance or disease in plants and animals. Although, at present, it must be a speculation to consider specific reactions of flavonoids and betalains with RSS, it is promising that the future investigations of S-containing phytochemicals including sulfated flavonoids or sulfoflavonoids will open up a new research field in life sciences.
\nIn modern science, a great number of studies have suggested health benefits of vegetable-based diets for humans. Many compounds identified from plants have been tested to evaluate their biochemical or pharmacological actions in prevention, mitigation and cure of diseases. According to the “one-to-one” principle, researchers have searched for novel bioactive phytochemicals that interact with specific target enzymes or molecules associated with disorders or diseases. The pharmacokinetic action of antioxidants, however, does not follow the “one-to-one” principle. The actual target is not a specific enzyme or protein but ROS. Since production of ROS is exclusively involved in any types of diseases including cancer, antioxidant activity of phytochemicals has attracted attention not only from researchers but also from the public due to their perceived “cure-all” actions. Nowadays, the antioxidant hypothesis described above has been accepted as the most probable explanation for the health benefits of vegetable-based diets.
\nRecent progress in medical science has clarified that unregulated RNS and RSS production are observed in many disorders or diseases, echoing findings from ROS research. Although a little is known how plants and animals might regulate RNS and RSS in the cells to achieve a fine balance, there is accumulating evidence to support the hypothesis that phytochemical antioxidants, such as flavonoids and betalains, also reduce the toxicity of RNS and RSS. The occurrence of nitrated flavonoids as well as sulfated flavonoids may imply the possible associations of the phytochemical antioxidants with RNS and/or RSS metabolisms in plants and animals. In this context, the term “antioxidant” for phytochemicals may need to be given a new name to reflect the latest research findings.
\nIn 2020, more than million people died due to the coronavirus disease 2019 (COVID-19) pandemic. There is no promising specific drug or treatment (as of December 2020) for the severe hospitalized patients. A “cytokine storm” occurs in severe cases of COVID-19 and the anti-inflammatory steroid dexamethasone has been applied to lower mortality [84]. COVID-19 and the common “cold” both present a syndrome of disease states. It seems unrealistic to rely on a single drug or chemical to cure the disease. In prevention of the infection, ascorbate and vegetables appears to be effective. The antioxidant flavonoids can reduce inorganic nitrite (NO2\n−) to generate NO in an acidic solution [85]. The vegetable diets and beverages such as the beet juice have been reported to prevent hypertension probably because of increase in NO bioavailability due to nitrite-dependent NO production [2, 86]. It is likely that vegetable-based foods and beverages could prevent or mitigate COVID-19 through their phytochemical antioxidant activities along with their provision of nitrate/nitrite supplementation [84, 87].
\nOxygen toxicity can be attributed ultimately to the biological evolution of oxygenic photosynthesis. In the ancient earth, H2S and NO concentrations are considered to have been much higher than the present day due to active volcanism [62]. The concentration of these “old” gasses fell down following the evolutional development of oxygenic photosynthesis in cyanobacteria [62]. It is presumed that most living organisms that were dominant at that time went extinct but some of them successfully developed antioxidant systems to cope with new oxic environments. The survivors from the lethal environments are the ancestors of the present animals. Even for plants, a high partial pressure of O2 made by photosynthesis is yet a great risk. To protect the photosynthetic apparatus, green plants have developed their unique antioxidant systems along with creation of many types of antioxidant molecules [88]. The left panel of Figure 6 represents a conceptual illustration for ROS, RNS and RSS in biological evolution in the earth history from past to the present. The order (ROSRNSRSS) can be found in ecological niches from surface to deep such as in soils (Figure 6, right). In the case of plants grown in the field, leaves are in oxic environments and roots are in hypoxic environments where there exists a gradient of O2, NO and H2S. Taking into account that sulfated plant phenolic compounds are found in plants inhabiting harsh environments, we consider it plausible that novel bioactive phytochemicals associated with RNS and RSS metabolisms might be found in the roots grown in such hypoxic environments [89].
\nThe ONS gradient in evolution and habitats. In plants, antioxidants can be found abundantly in leaves where oxygenic photosynthesis occurs, with a risk of overproduction of ROS. If oxidative stress is defined as a condition of disturbance of the fine-tuned redox balance, knowing the interplays among ROS, RNS and RSS is important for understanding cellular homeostasis. Oxygen tension would alter the best balance for each living organism in the field where there is the ONS (O2-NO-H2S) gradient from surface to the deep in soils, which also reflects the order of their evolutional development (from ancient to the present) [54].
Flavonoids and batalains are natural antioxidants that mitigate oxidative stress in plants and animals. In life sciences, oxidative stress can be defined as an imbalance of pro-oxidants and antioxidants in cells. Oxidative stress can be also defined as a disruption of redox signaling and control, emphasizing the importance of a dynamic but fine-tuned redox balance in cellular homeostasis [90]. According to this new definition, the ROS scavenging activity may be just a part of the pleiotropic functions of phytochemicals. Flavonoids and betalains could tune a fine redox balance through modulating the interplays among ROS, RNS and RSS. We are now entering into the next stage of plant “antioxidant” research.
\nWe thank Dr. Michael Cohen at the Sonoma State University for his critical reading of the manuscript. This work was partly supported by JSPS KAKENHI Grant Number JP19K06339 to H.Y.
\nThe authors declare no conflict of interest.
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\\n\\nIf you are interested in publishing your book with IntechOpen, please submit your book proposal by completing the Publishing Proposal Form.
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\n\nFor a complete overview of all publishing process steps and descriptions, go to How Open Access Publishing Works.
\n\nSEND YOUR PROPOSAL
\n\nIf you are interested in publishing your book with IntechOpen, please submit your book proposal by completing the Publishing Proposal Form.
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