Absolute reaction rate theory states that the rate of a chemical reaction requires that reactants first combine to form an activated complex,

k = κ ( k T / h ) K *

where k is the rate, κ is the transmission coefficient, kT/h has the dimensions of frequency and K^* is the equilibrium constant for the activated complex. The transmission coefficient, κ, for typical reactions approximates unity, i.e., each activated complex yields product, but not every activated complex at the potential-energy barrier will cross over to product [8]. The value of κ decreases by several orders of magnitude in reactions involving change in spin state [8].

The Wigner spin conservation rules state that a reacting system resists any change in spin angular momentum, i.e., multiplicity [9] [10]. The total spin number, S, of an atom or molecule defines its multiplicity; i.e., |2S| + 1 = multiplicity. When S = 0, the multiplicity is singlet, when S = 1/2, the multiplicity is doublet, when S = 1/2 + 1/2, the multiplicity is triplet, et cetera. Reactions involving change in multiplicity have transmission coefficient, κ, values of less than 10⁻⁴. The spin states or multiplicities of the reactants determine the spin state or multiplicity of the activated complex, and are conserved in the spin states or multiplicities of the resulting product or products. For example, if the impossibility of orbital overlap is ignored and reaction is assumed to involve a bosonic singlet multiplicity molecule and a bifermionic triplet multiplicity molecule, then the activated complex must have a bifermionic triplet multiplicity, and bifermionic triplet multiplicity must be conserved in the product or products. These and other possibilities are described in Table 1.

With regard to multiplicity, singlet-singlet reactions are allowed and yield singlet products. From a frontier orbital perspective, bosonic HOMO-LUMO interactions are allowed and yield bosonic products. For example, reaction of singlet multiplicity hypochlorite (OCl⁻) with singlet multiplicity hydrogen peroxide (H₂O₂) yields singlet multiplicity water (H₂O), singlet multiplicity chloride (Cl⁻) and electronically excited singlet multiplicity molecular oxygen ( O 1 2 ∗ ). Singlet multiplicity reactants produce singlet multiplicity products. Spin conservation requires O 1 2 ∗ , not triplet multiplicity ³O₂, as the product of the H₂O₂-OCl⁻ reaction. Production of O 1 2 ∗ is required for spin conservation, but violates Hund’s maximum multiplicity rule [11]. and as such, O 1 2 ∗ is electronically excited with a lifetime of about a microsecond [12]. As illustrated in Figure 2, O 1 2 ∗ relaxes to its triplet ground state by emitting a near infrared photon [13].

Bosonic frontier orbital interactions make up the vast majority of organic and biochemical reaction. Reactions involving a singlet with either a doublet, triplet or quartet multiplicity molecule must conserve spin. If bosonic-fermionic reaction occurs, the reaction product will retain the multiplicity of the fermionic reactant. Relative to frontier orbital considerations, such reactions require highly improbable LUMO-SOMO interaction. However, reactions involving doublet-doublet, triplet-triplet and quartet-quartet multiplicity reactants all yield singlet multiplicity products. Based on frontier orbital considerations, these fermion-fermion, bifermion-bifermion, and trifermion-trifermion reactions involve SOMO-SOMO interactions and produce bosonic products. The unfavourability of singlet-triplet, i.e., bosonic-bifermionic, reaction is well illustrated by considering the reaction of ground state triplet multiplicity (S = 1/2 + 1/2 or −1/2 + −1/2) molecular oxygen (³O₂) with a singlet multiplicity (S = 0) substrate molecule.

As illustrated in Figure 2, ³O₂ has two singly occupied frontier orbitals. As defined by Hund’s maximum multiplicity rule, the lowest energy or ground state of ³O₂ is achieved when both of its pi antibonding ( π g ∗ ) frontier orbitals have one electron, i.e., each π g ∗ orbital has the same m_s, i.e., 1/2 + 1/2 or −1/2 + −1/2 [11]. Since the two frontier orbitals of ³O₂ are both fermionic, ³O₂ is described as bifermionic. Oxygen is the second most electronegative element, and as such, organic oxygenation reactions are highly exergonic, but frontier orbital interaction are highly improbable, and combustion is not spontaneous.

Radicals react with radicals. Frontier orbital interactions involving SOMO-SOMO reactants are easily conceived. The products of such doublet-doublet reactions are singlet. In SOMO-SOMO reaction, the fermionic electrons of each SOMO couple to produce a bosonic product. For example, frontier orbital interaction of the fermionic π g ∗ SOMO of doublet multiplicity hydroperoxyl radical (²HO₂) with the fermionic π g ∗ SOMO orbital of doublet multiplicity superoxide radical ( O 2 2 − ) yields singlet multiplicity hydrogen peroxide (H₂O₂) and electronically excited singlet multiplicity molecular oxygen ( O 1 2 ∗ ) [14].

The role of ³O₂ in quenching the phosphorescence from relaxation of electronically excited triplet multiplicity dye (³dye*) is explained by triplet-triplet annihilation yielding bosonic products. This same triplet-triplet quenching is responsible for photodynamic action. Reaction of the electronically excited triplet dye (³dye*) with ³O₂ returns the dye to its ground state (¹dye) and photodynamically generates O 1 2 ∗ [15] [16].

To initiate burning, a sufficient amount of energy, e.g., a flame, must be applied to cause homolytic bond cleavage of the singlet multiplicity fuel molecule. Each homolytic cleavage yields two doublet multiplicity SOMO products. These fermionic products can directly react with the bifermionic frontier orbitals of ³O₂. Radicals react with radicals. As described in Table 1, reaction of a doublet multiplicity (i.e., S = 1/2) radical with triplet multiplicity (i.e., S = −1/2 + −1/2) molecular oxygen yields doublet multiplicity (S = −1/2) product, heat and light. In turn, the doublet multiplicity (S = −1/2) product can now react with another triplet multiplicity (S = 1/2 + 1/2) ³O₂, et cetera, resulting in reaction propagation, i.e., burning. Note that fermionic-fermionic reaction yields bosonic product, and that fermionic-multifermionic reaction yields the least fermionic product.

The neutrophil leukocyte, a phagocytic white blood cell, is tasked with defending the host animal against a vast variety of pathogenic microorganisms [17]. Fifty years ago, I pondered the possibility that phagocytic leukocytes kill microbes by changing the multiplicity of molecular oxygen from triplet to singlet [18]. From a frontier orbital perspective, changing bifermionic ³O₂ to bosonic O 1 2 ∗ opens the possibilities for bosonic electrophilic reaction with the bosonic molecular composition of microbes, i.e., bosonic combustion. Conventional fermionic combustions involve highly exergonic oxygenation reactions that generate electronically excited carbonyls that relax by emitting photons in the visible spectrum. The bosonic combustions of neutrophil leukocyte microbicidal action also involve highly exergonic oxygenations that generate electronically excited carbonyls with relaxation by photon emission. Light is emitted when neutrophil leukocytes phagocytose and kill opsonized microbes, and the photon emission or chemiluminescence is proportional to ³O₂ consumption and to glucose metabolism via the hexose monophosphate metabolic (HMP) shunt. As described in the section below, neutrophil leukocytes employ two mechanisms for the conversion of bifermionic ³O₂ to bosonic O 1 2 ∗ . The first involves fermionic-fermionic annihilation, and the second involves myeloperoxidase-mediated bosonic-bosonic reaction.

Neutrophil reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase controls HMP metabolism by accepting two reducing equivalents from NADPH thus liberating the oxidized NADP⁺ that is required for glucose-6-phosphate (G-6-P) dehydrogenase metabolism of glucose. Biochemical dehydrogenations involve hydride (H⁻) transfer. The bosonic character of such redox exchange will be considered subsequently. The riboflavin prosthetic group of NADPH oxidase facilitates decoupling of the bosonic electron pair. Riboflavin mediated separation allows fermionic expression of the separated electrons and results in reactive electron capture by bifermionic ³O₂ [14]. The product of such univalent reduction is the doublet multiplicity hydroperoxyl radical (²HO₂). ²HO₂ is an acid with a pKa of 4.8 that dissociates yielding a proton (H⁺) and doublet multiplicity superoxide radical ( O 2 2 − ). The reaction of fermionic ²HO₂ and fermionic O 2 2 − is a radical-radical annihilation yielding bosonic singlet multiplicity hydrogen peroxide (¹H₂O₂) and bosonic electronically excited singlet multiplicity molecular oxygen ( O 1 2 ∗ ) [19]. As described in Table 1, reactions of fermions yield bosonic products.

Neutrophils contain abundant myeloperoxidase (MPO). The haloperoxidase action of MPO provides an additional mechanism for generation of bosonic O 1 2 ∗ . MPO consumes the H₂O₂ and acid (H⁺) products of NADPH oxidase activity to oxidize chloride (Cl⁻) to hypochlorous acid (HOCl) or its conjugate base hypochlorite (OCl⁻). All of the reactants and products of MPO haloperoxidase action are singlet multiplicity and present bosonic frontier orbitals. The HOCl/OCl⁻ produced can further react non-enzymatically with additional H₂O₂ producing Cl⁻ and O 1 2 ∗ [20]. MPO can catalyze classical peroxidase activity involving radials, but such activity is distinct from the acid haloperoxidase action involved in microbicidal action [17].

Generation of O 1 2 ∗ violates Hund’s maximum multiplicity rule; i.e., the electronic configuration with highest multiplicity has the lowest energy. The greater the number of wave functions possible for a system, the lower the energy. Higher multiplicity states produce greater nuclear-electron attraction and are of lower energy [11]. As such, O 1 2 ∗ is metastable with a lifetime of about a microsecond. This lifetime restricts its potent electrophilic reactivity to within a radius of about 0.2 microns (µm) [12]. Upon phagocytosis, the microbe becomes the locus of neutrophil microbe killing. Generation of the bosonic reactant O 1 2 ∗ within the phagolysosome space of the neutrophil directly focuses its potent electrophilic reactivity to the target microbe and minimizes collateral damage. Purified MPO selectively binds all gram-negative bacteria tested and can bind and inactivate endotoxin even in the absence of haloperoxidase function [21]. Selective MPO binding to microbes correlates with selective MPO-mediated microbicidal action. Bosonic combustion is limited by the lifetime of O 1 2 ∗ . Such reactive restrictions have the advantage of selectively focusing and confining combustive action to the microbe while avoiding bystander injury to host cells [22].