The Theory of Conjugate Reactions in the Context of Modern Ideas

Various types of possible interactions between reactions are discussed. Some of them are united by the general idea of chemical reaction interference. The ideas on conjugated reactions are broadened and the determinant formula is deduced; the coherence condition for chemical interference is formulated and associated phase shifts are determined. It is shown how interaction between reactions may be qualitatively and quantitatively assessed and kinetic analysis of complex reactions with under-researched mechanisms may be performed with simultaneous consideration of the stationary concentration method. Using particular examples, interference of hydrogen peroxide dissociation and oxidation of substrates is considered.

cal kinetics as the law of the masses and the independence of the course of elementary reactions are fulfilled and retain their inviolability.
Energy aspect of the conjugate processes is discussed in [9] in the framework of thermodynamics of irreversible processes.
Despite the fact that the basics of conjugate reactions were formulated at the beginning of the 20th century, nowadays they have found their "second wind" as part of the creation of innovative technologies that mimic useful functions of the processes occurring in nature (in particular, enzymatic catalysis). It should be considered that despite the fact that the theory of conjugate reactions was developed at the time when there was almost no information about detailed mechanism of chemical reactions, it nevertheless remains true on its fundamental basis. However, the old theories "cannot be revived to life in their literal interpretation".
Characteristic features of the conjugate reactions formulated by N.A. Shilov in his monograph [8] consist of following regulations: -an exergonic reaction performs useful work for the flow of another-endergonic-reaction, i.e. a loss of free energy in a primary reaction fully covers an increase in free energy in a secondary reaction; -communication channels between conjugate reactions are established through common intermediate compounds; -conjugate reactions necessarily occur in open systems; -conjugated reactions must be complex.
We have added to this list a number of classical regulations of chemical kinetics.
It is necessary to add new regulations as Shilov's monograph [8] was published in 1905, when such highly active intermediate substances as free radicals, active complex compounds, etc. were not known. Undoubtedly, in the kinetics of conjugate reactions along with the law of masses, the fundamental chemical postulate of the independence of elementary reactions is unbreakable.
Possibility of occurrence of conjugate reactions only in open systems is associated with the requirement of the system to have a constant mass exchange with external environment. This regulation radically distinguishes conjugate reactions from initiated, catalytic, autocatalytic and polymeric processes that can occur in close systems.
The fact that conjugate reactions must necessarily be hindered is explained by the fact that only they (because of their complexity) may have common highly The main subject of this article is discussion and terminological clarification of fundamental issues related to the kinetics of interaction of the complex reactions (chemical interference).
However, it is necessary to demonstrate differences between various synchronous (i.e., simultaneously occurring) reactions-parallel, sequential, parallel-sequential, conjugate and coherent-synchronized reactions (see Figure 1).
Where А → В is the primary reaction; А → С is the secondary reaction.
As can be seen from the diagram, the most significant distinguishing feature of conjugate and coherently synchronized reactions from other reactions is their coherence (consistency).
It is necessary to consider the regulations stated below in order to understand these differences: -the secondary (target) non-induced reaction is a non-spontaneous or self-induced reaction, which is difficult to realize due to kinetic and thermodynamic order; -during induction, type of the target (secondary) reaction is transformed from non-spontaneous to self-induced and, under realizable conditions, it flows without difficulty; -a gross equation of the secondary reaction is already formed in its induced form, i.e. in a transformed form; -in contrast to parallel, sequential and parallel-sequential reactions, an induced (secondary) reaction cannot be carried out separately from the primary reaction; -the spontaneous target reaction can also be modified under influence of induction and under certain conditions proceed with a high rate; -the reaction system, in which chemical induction is realized, contains two or more components. The concept of chemical interference is put forward by us, as a phenomenon consisting in the fact that reactions occurring synchronously in a chemical system, can mutually strengthen and weaken, and in this state they are necessarily coherent [1]- [6].
Mathematical apparatus of the chemical interference and, in particular, coherent-synchronized reactions  (where A is an actor, In is an inductor, Acc is an acceptor and X is a highly active particle) consists of the determinant equation [1]- [6]: ( ) f are the actor consumption in the primary and secondary reactions) and the coherence ratio: On the basis of these equations, a determinant scale was compiled. It is easy to determine in the reaction medium the nature of an intervention of one reaction into another (chemical interference) using this scale: D = 0 ÷ ν is the area of chemical conjugation; D > ν is the area of other interrelated interfering reactions.
The scheme shows that the synchronous reactions which are not coherent, but one interferes with another, can be present in the chemical system (for example, initiated, catalytic and autocatalytic reactions, etc.).
A kinetic study of the chemical system where an interaction of reactions takes place, allows us to make a choice between various types of interfering chemical reactions on the basis of experimental data. Therefore, the study of chemical interference may be useful in an investigation of mechanisms of complex reactions.
In this respect, a determinant equation is an easily adaptable kinetic apparatus for solving complex chemical problems.
Thus, the determinant equation and a scale of chemical interference built on its basis make it easy to distinguish conjugate and coherent synchronous reactions from catalytic, initiated, free-radical reactions, autocatalytic and other reactions, which is practically difficult to do. According to Ostwald and Shilov [8], only the complex reactions can conjugate, and not the elementary stages that constitute mechanisms of the primary and secondary reactions. In the primary reaction, due to the elementary stage, a highly active intermediate particle is generated into the system, and then consumed through two channels (the primary and secondary reactions). This elementary   [7].

Chemical Interference-Intervention of One Reaction into Another
A similar erroneous statement in [9]   The scheme in [7] is absolutely incorrectly taken as the basis of their understanding of the theory of conjugate reactions, which is illustrated by the following statement: "A classic example of a process with chemical induction is the oxidation of benzene to phenol, which proceeds in conjunction with the oxidation of Fe 2+ by hydrogen peroxide (Fenton's system)".
This reaction system is classical and is considered in many textbooks and monographs as a vivid example of conjugation of two gross reactions-oxidation of Fe 2+ by hydrogen peroxide (Fenton reaction) and oxidation of benzene to phenol by hydrogen peroxide.
Fenton reaction: Ions of iron (II) in the liquid phase are oxidized by hydrogen peroxide to Fe (III) ions, which are later converted back to iron (II) affected by hydrogen peroxide [11]: It follows from the reactions (8) and (9)  reactions. Summing up these arguments, we see the fallacy of the statement in [7] that the oxidation reaction of benzene to phenol proceeds in conjunction with the oxidation of Fe 2+ with hydrogen peroxide. Moreover, the catalyst can be neither an actor nor an inductor, since the inductor and the actor should be consumed during the reaction [8].
It is noted in [7] that the actor consumption in the conjugate reactions is de-  (2): "how much actor is consumed in the primary reaction vA + In, which is the initial stage of X formation-the bifurcation center, where reaction 1 is responsible for the formation of the final products of the primary reaction and reaction 2 for the formation of the secondary reaction products". In other words, the scheme (2) demonstrates a simple regulation that the actor is consumed exactly as much as it is necessary for the formation of X in primary reaction and this absolutely does not contradict the material balance. There is the following phrase in [7] "the reaction with H 2 O 2 hinders the development of the chain process of H 2 O 2 decomposition" that I was credited with, which is not found in the monograph [4]. Surprisingly, this phrase is given in brackets, thus it is difficult to figure out what is meant by the authors. Moreover, the use of dubious approaches for the approval of their own ideas leads authors [7] to the absurd. Complex reactions can be in conjugation in the case when they have a common source substance-actor. However, this is a necessary but not sufficient condition. A sufficient condition is the presence of highly active intermediate common for these reactions. The combination of these two conditions fundamentally distinguishes conjugate processes from parallel and other complex reactions that have a common source substance.
Another expression from the same page: "The basic reaction (III) can proceed in parallel with the reaction (XVII) through a common intermediate". Parallel reactions and the general intermediate reflect a continuous confusion that underlies the so-called "Kinetic conjugation". There is a simple and clear trivial expression "kinetics of conjugate reactions" which does not allow such distortions in kinetic terminology.
"The sequential reactions (stages) mutually influence the flow rate of each other due to changes in the concentration of the common intermediate" (p. 281 [7]). Mutual influence of the successive stages through the "common intermediate" contradicts the concept of sequential reactions. The intermediate formed in the first elementary stage, as its final product, is the starting point for the second stage, etc. and their course obeys the principle of independence of the course of elementary stages.
The intermediate common for two conjugate reactions undoubtedly changes the mechanism of the secondary reaction and, naturally, this circumstance affects the kinetics and thermodynamics of the conjugated process [1]- [6].
Concerning the following expression on p. 281 [7] "... thermodynamic conjugation occurs in the case of simple parallel reactions", it can be stated that simple It is also stated on page 282 [7] that "... the kinetic conjugation of the stages is a characteristic feature of all complex reactions". According to the authors all known complex chemical reactions are conjugate, and their notion of "kinetic conjugation" leads to this false conclusion.
Their reasoning indicates that "The main feature of unbranched and branched chain processes is the kinetic conjugation of two or more routes ...", which leads to a complete confusion.
It is given on page 286 [7] that "... the flow of the parallel reactions, which do not have common with the main process reagents (parallel reactions always have one common reagent) and intermediates, does not make the endoergic process thermodynamically possible. It was shown above that interrelation of rates takes place only with the presence of common intermediates in sequential and parallel-sequential reactions (i.e., with the presence of the kinetic conjugation)...".
We have already mentioned above that parallel, sequential, parallel-sequential, as well as conjugate reactions are completely independent kinetic concepts. They are considered within the framework of complex gross reactions and bringing them into one concept of "kinetic conjugation" is scientifically meaningless.
The authors [7] analyze another phrase from my book [1]: "For example, the first characteristic feature of conjugate reactions according to Nagiev ([4] p. 38) is as follows: '... the decrease in free energy in the primary reaction fully covers the increase in free energy in the secondary reaction.' As we have noted above, this situation is impossible in the classical scheme by Shilov, since the product of the primary reaction (I) P2 is not included in the final equation of the conjugate reaction." However, according to Shilov ([8], p. 11) "... in view of the fact that an inductor enters a reaction that proceeds arbitrarily (the primary process) and undergoes chemical transformation, the free energy released by it can compensate for the formation of a substance that requires work input." I.M. Emanuel and Knorre [9] stated in the textbook on chemical kinetics the following: "In order for the reaction to proceed with an increase in free energy, a source of power (free energy) is necessary. An inducing reaction can be such a source. The free energy released by an inducing reaction must be greater than the free energy absorbed by the induced reaction. The use of free energy released in chemical reactions for the implementation of other reactions associated with the first processes is crucial in biological systems".
The formulations given in [9], from a thermodynamic point of view, unambiguously indicate the fundamental role of "free energy released in the primary reaction to cover the free energy" of the endothermic reaction-so that the latter secondary reaction becomes spontaneous.
The main thesis of the authors against these formulations, including mine, is that "the product of the primary reaction is not included in the final equation of the conjugate reaction".

T. Nagiev Advances in Chemical Engineering and Science
There is a complete misunderstanding in [7] of the fact that the highly active intermediate particle generated by the primary reaction, due to bifurcation, transforms the secondary thermodynamically obstructed reaction into a spontaneous one. At the same time, the stage mechanism of a complex secondary reaction always includes elementary reactions responsible for the formation of a common, highly active intermediate particle in the mechanism of the primary reaction. Thus, along with the common highly active particle, conjugate reactions have at least one common elementary reaction.
Interaction of reactions, as is known, occurs through a common highly reac- Thus, on page 286 [7] there are confused arguments on the following "in the presence of common intermediates in sequential or parallel-sequential, (i.e., kinetic conjugation), a correlation of rates occurs ...", which introduces formulations into chemical kinetics, that distort its basis.
Let us consider the mechanisms of sequential and parallel-sequential reactions, described in [7]: where C, and D are the final products that can be isolated, i.e. quite stable compounds. Substance B is an intermediate stable product of sequential and parallel-sequential reactions, and not a highly active common intermediate, due to which the conjugation of reactions is carried out in the system.
If we assume that substance B in the reaction (12) is a highly active common intermediate, then it ceases to be parallel-sequential in the accepted sense, and becomes the stage of the conjugate primary reaction. In this case B is the link between the two conjugate gross reactions, and its bifurcation leads to the formation of the final products C and D. Thus there is no need to mention sequential and parallel-sequential reactions, as is done in [7].
Only gross reactions that have a common, highly active intermediate which is a bifurcation center that cannot be isolated from the reaction medium can be conjugated. We have already noted above that in order to form a new modified mechanism of the secondary reaction, elementary stages are taken from the mechanism of the primary reaction, leading to the formation of a common highly It is important to take into account the fact that common elementary stages of the primary and secondary reactions cannot functionally be a bifurcation center.
The bifurcation center is their common intermediate, which is consumed in the subsequent stages of the conjugate reactions.
It is further stated in [7] that "... a decrease in free energy in the primary reaction fully covers the increase in free energy in the secondary reaction", this is impossible because the product of the primary (1)-P2 is not included in the final equation in the conjugate reaction (XVII). It is given in the textbook [12] and the monograph [13] that the joint occurrence of spontaneous ("conjugate", In the first place, the primary reaction cannot fully enter the mechanism of the secondary reaction due to the fact that they are two independent gross reactions with their characteristic end products. Another thing is when the elementary stages of the primary reaction (see above) lead to the occasion when they participate in a transformation of a non-spontaneous secondary reaction into a spontaneous one with the help of the formed highly active intermediate substance (intermediate). Free energy of a chemical reaction is usually calculated from state of substances, in their initial and final states. Another way is when a stage mechanism of a complex reaction is known, wherein its free energy will be the sum of free energies of each elementary stage. This implies that the sum of the free energies of the elementary stages, which lead to the generation of a common highly active intermediate in the system, is added to the sum of the free energies of the subsequent stages, leading to the secondary reaction. Shilov, proceeding from the knowledge of his time (1905), justifiably believed that the free energy of the conjugating primary reaction should completely cover the free energy of the thermodynamically hindered secondary reaction. Based on today's knowledge, we see that both approaches lead to identical conclusions and the authors of [12] [13] quite rightly use Shilov's approach.
Thus, the final equation of the secondary reaction transformed into the spontaneous one should not include the final products of the primary reaction, as it is T. Nagiev Advances in Chemical Engineering and Science should be noted that these concepts have no relation to the features of conjugate reactions or to the effect of thermodynamic conjugation. Pseudo-scientific terminology only obscures reasonably clear kinetic effects".
Synchronous reactions are nothing but simultaneous reactions and it is not quite clear why it is impossible to use this expression in this sense. The term "chemical interference" means that the primary reaction interferes with the flow of the secondary reaction and thereby conjugates with it. The authors' reaction [7] to this appropriate analogy is quite surprising. If I had used the expression "conjugate intervention of one reaction into the flow of another" instead of "conjugate interfering reactions" the authors [7] would not supposedly react negatively. It has already been noted that interfering (i.e. interfering into the flow of each other) reactions can be conjugate, initiated, catalytic reactions, etc.
The expression "coherence of chemical interference" means the consistency of chemical intervention of one reaction into the flow of another, and there is nothing unclear about it.
While claiming that "these concepts have no relation to the features of the conjugate reactions or to the effect of thermodynamic conjugation", the authors of [7] obviously did not understand obvious things and therefore we are not able to figure out their motive when they claim these quite clear terms as "pseudoscientific".
Based solely on their false notions that "Conjugation of the primary and secondary reactions according to Shilov is the kinetic conjugation of the elementary stages ..." the authors deny a validity of the existence of "thermodynamic conjugation" in "conventional understanding".
Summarizing all the above, we recall once again that simple reactions, due to their elementary nature, can never be conjugated, however much they are covered by "pseudoscientific terms" (as stated by the authors of [7]) such as "kinetic conjugation", "conjugation of elementary reactions", etc. Therefore, the statement on p. 282 [7] that "Kinetic conjugation of stages is a characteristic feature of all complex reactions" means only one thing: almost all complex chemical reactions known in nature are conjugate, and this contradicts the existence of a huge number of complex reactions outside of the system of conjugate reactions. His concept of the interference of chemical reactions is a natural generalization and a non-trivial development of N.A. Shilov's idea of conjugate oxidation reactions". Only scientific practice will show whether the new concept of "interference of chemical processes" will be viable or not.

Conclusions
The strategy associated with imparting high efficiency and orderliness to chemical interference has proved itself: 1) The primary reaction runs with almost 100% conversion in the absence of the secondary reaction; 2) It approaches 100% selectivity for both reactions.
The study of chemical interference and its particular case of conjugated processes indicate that it may represent a simple prototype for similar systems realizable in biochemical systems.
First of all, realization of chemical interference is associated with the selection of those reactions that are capable of self-organization, i.e. to formation of complex reaction ensemble. The ensemble of molecules and, as a consequence, the ensemble of reactions is able to interfere, because the aggregation of molecules in ensembles somehow creates an algorithm for the realization of mutually agreed spontaneous reactions. Contrary to free molecules, the distinctive feature of an ensemble of molecules is the fact that structural organization of an ensemble of molecules allows running of both simple and complex reactions, chemical interference of which is vitally important for the living system activity. In this discussion we would like to indicate that chemical interference is the necessary property of biochemical systems. Note also that molecular ensembles may be differently organized structurally and, therefore, the type of ensemble from the same molecules is responsible for proceeding of one type of interrelated reactions or another (i.e. chemically interfering reactions).
The ensemble of reactions is self-organized through the intermediary of general highly active substances. These processes may be accelerated and effectively implemented with the help of catalysts similar to processes, which take part in the living systems.
Thus, self-organization of an ensemble of reactions capable of being intensified or weakened and, therefore, inducing chemical interference, may be suggested as the basis for the principle of organization of many enzymatic ensembles.
Of great interest is the creation of trigger reaction ensembles, which will not only change the interference picture but also the type of interacting reaction with respect to the action of temperature, pressure, medium pH and other important factors.

Conflicts of Interest
The author declares no conflicts of interest regarding the publication of this paper.