considered as an organ , the collective mass of hematopoietic bone marrow in a healthy adult is greater than that of the liver .
the major proportion of this hematopoietic activity is directed to producing neutrophil leukocytes . each day a healthy human adult releases about a hundred billion neutrophils into the circulating blood .
this baseline production is greatly expanded in inflammatory states and by treatment with a granulocyte - colony stimulating factor ( g - csf ) such as filgrastim .
in addition to stimulating neutrophil hyperplasia , that is , increased production , g - csf treatment also results in hypertrophic changes , that is , larger neutrophils with severalfold greater azurophilic granule content and proportionally increased myeloperoxidase ( mpo ) .
the neutrophil serves as the principal leukocyte of the acute inflammatory response and is the primary microbicidal phagocyte of the innate and acquired immune defense systems . accomplishing such
when stimulated by microbial products , complement activation peptides , cytokines , et cetera , neutrophils fuse their specific ( a.k.a . , secondary ) granules with their cytoplasmic membrane ( i.e. , specific degranulation ) , thus providing the increased surface - to - volume ratio necessary for locomotion and exposing the cytokine receptors and opsonin receptors required for close endothelial contact and diapedesis ( i.e. , transit ) from the vascular space through the endothelial lining into the tissue interstitial space .
chemotactic locomotion to the site of infection is directed by concentration gradients of bacterial products , anaphylatoxin , cytokines , et cetera .
contact and receptor - mediated recognition of an opsonified ( e.g. , complement- , immunoglobulin - labeled ) microbe results in phagocytosis , formation of a phagosome , and fusion with azurophilic ( a.k.a .
the morphologic changes of phagocytosis are associated with magnitudinal increase in hexose monophosphate shunt metabolism of glucose and with proportionally increased molecular oxygen ( o2 ) consumption , that is , the respiratory burst .
this mitochondria - independent metabolic activity is required for effective microbicidal action [ 5 , 6 ] .
the resulting microbicidal oxygenation reactions have exergonicities sufficient to produce electronic excited products yielding light emission in the visible spectrum , that is , chemiluminescence or luminescence .
two reducing equivalents ( i.e. , two electrons ( e ) plus two protons ( h ) ) are transferred from nadph to the oxidase where they distribute in a manner allowing for univalent ( one equivalent ) reduction of o2 , yielding hydrodioxylic acid ( ho2 ; a.k.a .
ho2 is an acid with a pka of 4.9 and , as such , dissociates yielding a proton and its conjugate base , the superoxide anion ( o2 ) .
production of ho2 within the neutrophil phagosome or phagolysosome dynamically acidifies the confined space . as the ph of the space approaches the pka ( i.e. , 4.9 ) , the ratio of ho2 to o2 approaches unity , removing the anionic barrier to direct radical - radical disproportionation [ 10 , 11 ] . in such acidic milieu
, ho2 reacts directly with o2 to produce hydrogen peroxide ( h2o2 ) and singlet molecular oxygen ( o2 ) [ 1012 ] .
these activities provide the optimal milieu and h2o2 substrate for myeloperoxidase ( mpo ) oxidation of chloride ( cl ) to the chloronium ( cl ) state yielding hypochlorous acid ( hocl ) .
spontaneous reaction of hocl with an additional h2o2 yields cl , h2o , and o2 .
the order of electronegativity values for fluorine ( f ) , oxygen ( o ) , and chorine ( cl ) is 4.0 , 3.5 , and 3.0 , respectively .
the energy difference separating o2 from water ( h2o ) is large , that is , a difference of 1.23 volts ( v ) or 96.5 kilocalories per mole ( kcal  mol ) , and provides the driving force of life on earth .
the merriam - webster dictionary defines combustion as a chemical reaction that occurs when oxygen combines with other substances to produce heat and usually light . as such
the heat of reaction calculations for the reaction of o2 with ethylene liberates 93  kcal  mol ( i.e. , 389 kilojoules per mole ( kj  mol ) ) or the energy equivalent to an einstein ( i.e. , one mole ) of ultraviolet photons .
the electronegativity of oxygen predicts the high exergonicity of oxygenation reactions , but such reactions are not spontaneous . placed together in a chamber , o2 does not react with ethylene . for reaction to occur ,
a photon or spark with energy sufficient to initiate ethylene bond homolytic cleavage must be applied .
this presentation addresses the questions : why does not oxygen spontaneously react with organic material ?
why is oxygen reduction , a process that decreases its thermodynamic potential , required as a first step for neutrophil combustive microbicidal action ? and what is the best viewpoint for considering oxygen reactivity ?
the review provides the background physics and chemistry for a fundamental perspective with regard to oxygen reactivity in particular , neutrophil combustive microbicidal action with its associated luminescence , and reaction chemistry in general .
hopefully , it will encourage interested researchers out of their comfort zone and broaden their scientific outlook .
particles are of two symmetry types , each with unique statistical mechanical properties [ 17 , 18 ] .
they are either bose - einstein particles ( bosons ) or fermi - dirac particles ( fermions ) . according to the exchange principle ,
a pair of particles , that is , a and b , can be described by a wave function , (a , b ) , representing the space and spin coordinates of the particles .
even if the particles are indistinguishable ( e.g. , electrons ) , the particle sites are distinguishable .
each site is unique with regard to its spin - state , that is , spin - up (  ) or spin - down (  ) .
exchange can be symmetric : (a , b ) = (b , a ) ; or exchange can be antisymmetric : (a , b ) = (b , a ) .
the wave functions of bosons are symmetric to exchange of a pair of particles ; that is , (a , b ) = (b , a ) .
bosons obey ordinary commutation ; a  b = b  a. rotating a boson through 360 degrees , 360   , returns it to its original state .
. photons , the force carrier particles of electromagnetic energy , are bosons and are described by the planck equation : e = h , where e is energy , h is planck 's constant , and  is frequency .
such products include large bosons with mass , such as alpha (  ) particles .
the character of atomic and molecular orbitals can likewise be considered as bosonic or fermionic . as will be developed subsequently , the frontier orbital of an atom or molecule is bosonic if composed of paired antisymmetric electrons . as such ,
the wave functions of fermions are antisymmetric to exchange of particles ; that is , (a , b ) = (b , a ) .
fermions are characterized as having half - integer spin and appear as multiples of the basic unit ( 1/2) , where  ( h - bar ) equals planck 's constant ( h ) divided by 2. fermions anticommute ; that is , a  b  b  a. rotating a fermion through 360 degrees , 360   , changes the phase but does not return the fermion to its original state .
an additional 360 degrees ' rotation , 360   , is required to return the antisymmetric particle to its original state .
the frontier orbitals of atoms , such as hydrogen ( h ) , nitrogen ( n ) , and oxygen ( o ) , and molecules , such as o2 and nitrous oxide ( no ) , have singly occupied atomic or molecular orbitals ( so(a)mo ) .
atoms and molecules with fermionic orbitals are radical and paramagnetic . atomic hydrogen ( h ) is composed of a positively charged nuclear proton ( h ) and a negatively charged electron ( e ) .
h is thousandfold more massive than e , and , as such , the kinetic and potential energies of e are described as its  orbit  relative to the massive h. the orbital wave function describes the energy possibilities . using polar coordinates ,
the position of e can be described as its distance , r , from its nucleus and two angles ,  and . the total wave function is isolated into 3 separate contributions , (r ,  ,  ) = r(r)()( ) , where r(r ) is the radial component and ( ) and ( ) are the angular components .
the radial component yields the principal quantum number , n. the angular components yield the azimuthal quantum number , l , and the magnetic quantum number , ml .
the degree of orbital degeneracy is the square of the principal quantum number , n. when n = 1 , the degeneracy is 1 = 1 , yielding the 1s orbital .
when n = 2 , the degeneracy is 2 = 4 , yielding the 2s , 2px , 2py , and 2pz orbitals .
the azimuthal quantum number , l , describes the shape of the orbit and the orbital angular momentum of e. the magnetic quantum number , ml , describes the number of orbitals with a given value of l. the value of the total orbital angular momentum , l , is l = [l(l + 1)] .
this intrinsic quantum mechanical property , that is , spin , is described by the spin quantum number , s. the magnitude of s is restricted to a value of 1/2 .
the total spin angular momentum , s , of a system is expressed by the equation s = [s(s + 1)] .
the intrinsic spin with its value of ( 1/2) ( abbreviated to 1/2 ) is a quality of fermions without analogy in classical physics .
just as l gives rise to ml , s gives rise to the spin quantum number ms .
only two values are allowed for ms . when ms = 1/2 , e is described as spin - up (  )
; when ms = 1/2 , e is described as spin - down (  ) .
each e of an atom or molecule is defined by its five quantum numbers : n , l , ml , s , and ms . the pauli exclusion principle states that no two electrons of a given atom can have identical quantum numbers ; that is , the total wave function for a system must be antisymmetric to the exchange of any pair of electrons . for an orbit to accommodate two electrons , the electrons must have opposite spins . if one orbital e has ms = 1/2  (  ) , the other orbital e must have ms = 1/2  (  ) . as such , the total spin quantum number , s , for an orbital electron - couple is 1/2 + 1/2 = 0  (    ) .
orbital coupling of the fermionic electrons results in spin - neutralization . in effect , the antisymmetric fermions combine into a symmetric boson .
this concept is illustrated in figure 2 by the reaction of two h atoms to generate molecular h2 .
multiplicity is a spectroscopic term and indicates the number of wave functions possible for the system ; that is , singlet indicates 1 , doublet indicates 2 , triplet indicates 3 , et cetera . in its ground ( lowest energy ) electronic state , atomic h has a single e in the 1s orbital and has an s value of 1/2 or 1/2 ; thus |2(1/2  or  1/2)| + 1 = 2 ; the multiplicity is doublet . for molecular h2
the value of s is 0 ; thus , |2(0)| + 1 = 1 ; the multiplicity is singlet . in figure 2 ,
the spin quantum number of each e is represented as spin - up ( ms = 1/2 =  ) or spin - down ( ms = 1/2 =  ) .
the circle surrounding the  orbital electron - couple of the homo of h2 symbolizes the bosonic character of the filled orbital .
when the electrons are antisymmetric , that is ,  and  , overlap is constructive resulting in chemical bonding ; that is , there is an increased probability of finding electrons in the internuclear region between the two h nuclei .
combining the two atomic 1s orbitals yields the bonding sigma molecular orbital , . note that bonding lowers the energy of the system . when the electrons are  and  or  and  , the overlap is destructive and no bonding occurs .
frontier orbital theory focuses on the initial orbital conditions of the reactants and on reactive transition with special emphasis on the highest occupied and lowest unoccupied orbitals [ 21 , 22 ] .
the frontier orbitals , that is , the highest occupied atomic or molecular orbital ( ho(a)mo ) and the lowest unoccupied molecular orbital ( lumo ) , define the reactive possibilities . as depicted in figure 2 ,
the electrons of the singly occupied atomic orbital ( soao ) of the two h atoms constructively overlap in a radical - radical ( i.e. , doublet - doublet ) annihilation producing the  bonding homo orbital of singlet multiplicity , diamagnetic molecular hydrogen ( h2 ) . for the h atoms ,
the electrons of the 1s orbitals have identical energies , but with covalent bonding to form h2 , the wave functions overlap and split producing two molecular orbitals , one with lower and one with higher energy than the original 1s atomic orbitals .
the bonding orbital (  ) is lower in energy and stable , thus promoting bonding .
the antibonding orbital (  ) is of higher energy . populating the antibonding orbital promotes bond breaking .
consequently , if a photon of sufficient frequency is captured by a  electron , its electronic excitation to the  orbital results in h2 bond cleavage .
the wigner - witmer spin conservation rules describe reaction symmetry possibilities in terms of reactant and product multiplicities [ 24 , 25 ] .
the spin conservation rules state that the overall spin angular momentum of a system must be conserved .
reactant and product state possibilities can also be considered in terms of fermionic and bosonic frontier orbital character . in table 1
reactants and products are presented in terms of multiplicity and also in terms of bosonic or fermionic orbital character . as depicted in figure 2 ,
combining two doublet multiplicity h atoms produces singlet multiplicity h2 . with regard to orbital spin character ,
the two antisymmetric fermionic electrons of the atomic orbitals are coupled ( condensed or combined ) resulting in the bosonic electron pair of the  orbital of h2 .
since the pauli principle requires the total wave function for any system of electrons to be antisymmetric to exchange an orbital pair of electrons , only phase - opposite electrons can occupy a given orbital state .
hund 's maximum multiplicity rule states that 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 .   figure 3 depicts the combination of two nitrogen atoms ( n ) to yield molecular nitrogen ( n2 ) .
ground state atomic n is a paramagnetic triradical with one electron in each of its three 2p orbitals .
note that each electron has the same ms value resulting in quartet multiplicity ; that is , |2(3(1/2  or  1/2))|+1 = 4 .
combining the atomic orbitals of the two quartet multiplicity nitrogen atoms ( n ) generates the filled ( bosonic ) ( 1s and 2s )  and  orbitals ; constructive overlap of the phase - opposite electrons of the three 2p orbitals of the two n atoms generates one  and two  bonds of triple - bonded ground state singlet multiplicity n2 .
the triradical n atoms combine to produce nonradical n2 . from the fermion - boson frontier
orbital perspective , each n presents a complex of trifermionic soaos , that is ,  ( i.e. , s = 3(1/2 ) ) or  ( i.e. , s = 3(1/2 ) ) .
consistent with table 1 , antisymmetric coupling produces triple - bonded bosonic ( i.e. , s = 0 ) n2 .
frontier orbital overlap of two oxygen atoms with antisymmetric somo is constructive producing o2 as depicted in figure 4 . as per table 1 , combining two ground state triplet multiplicity paramagnetic , diradical oxygen atoms ( o ) produces an electronically excited singlet multiplicity , diamagnetic , nonradical o2 .
note the product o2 obeys the spin symmetry rules but violates hund 's maximum multiplicity rule .
as such , o2 is electronically excited ( indicated by  ) with an energy of 22.5  kcal  mol greater than that of triplet multiplicity ground state o2 .
the spin conservation rules predict that the change in spin multiplicity , that is , a singlet - to - triplet transition , is of low probability .
as such , electronically excited o2 is metastable with a relatively long half - life .
the estimated four - microsecond lifetime of o2 is sufficient to allow its participation as an electrophilic reactant in dioxygenation reactions .
however , such reactions are restricted to within a radius of about 0.2 microns ( m ) from its point of generation [ 27 , 28 ] . as depicted in figure 5 , unreacted o2 relaxes to its triplet multiplicity ground state ( o2 ) by emitting a 1270  nm ( near infrared ) photon . as per the maximum multiplicity rule ,
ground state molecular oxygen is a triplet multiplicity , paramagnetic diradical with one e occupying each of its two  somos ; it is bifermionic .
ground state o2 can be in either the  ( i.e. , s = 1/2 + 1/2 = 2(1/2 ) = 1 ) or the  ( i.e. , s = 1/2  1/2 = 2(1/2 ) = 1 ) state ; thus , the multiplicity is |2(1 ) + 1| = 3 , that is , triplet .
the vast majority of biological molecules are singlet multiplicity  that is , s = 0and , as such , present bosonic frontier orbitals . for such molecules
, chemistry is confined to bosonic homo - lumo exchange of a composite orbital electron - couple .
antisymmetric fermionic frontier orbital overlap is constructive resulting in covalent bonding of the bosonic singlet product .
as described in table 1 , constructive somo - somo overlap of a doublet reactant and a triplet reactant produces a doublet product ; that is , the fermionic character is preserved .
direct reaction of ground state triplet multiplicity o2 with singlet multiplicity organic molecules violates the spin conservation rules , and , as such , combustion is not spontaneous .
overlap of the bifermionic  ( the 2 somo ) frontier orbitals of triplet multiplicity o2 with the empty lumo or bosonic homo of singlet multiplicity organic molecules is not constructive .
such reactions are symmetry - restricted , and the only product possible would also be a bifermionic triplet . o2 with its triplet multiplicity ground state
the relaxation of such excited triplet multiplicity molecules to their singlet ground state , that is , triplet - to - singlet transition , violates the conservation rules and is of low probability .
the delayed relaxation of an excited triplet to its singlet ground state by photon emission is responsible for the phenomenon of phosphorescence . considering the complexity and variety of potentially pathogenic organisms
, neutrophil microbicidal action must be simple , potent , and focused so as to maximize microbicidal action and minimize collateral damage .
microbicidal combustion is realized by changing the frontier orbitals of oxygen from bifermionic to bosonic .
oxygenation reactions yield electronically excited products that relax to ground state by emission of light in the visible spectral range .
respiratory burst metabolism mobilizes the reducing equivalents required for changing the frontier orbitals of o2 .
when it does occur , the semiquinone of a riboflavin prosthetic group is typically involved .
such flavoenzymes mark the departure from two equivalent cytoplasmic transfers to one equivalent cytochrome transfer .
one equivalent reduction of o2 changes its multiplicity from triplet to doublet , thus reducing its overall fermionic orbital character .
the flavocytochrome enzyme nadph oxidase catalyzes the reduction of bifermionic triplet multiplicity o2 to fermionic doublet multiplicity ho2 [ 9 , 10 ] .
acidic dissociation of ho2 yields its conjugate base , doublet multiplicity superoxide anion ( o2 ) . as per figure 1 and table 1 , direct somo - somo orbital overlap of ho2 with o2 produces singlet multiplicity ground state h2o2 plus o2 [ 10 , 12 ] .
the h2o2 produced serves as substrate for myeloperoxidase ( mpo ) oxidation of chloride producing hypochlorous acid ; that is , h2o2 + cl h2o + hocl .
this reaction involves the bosonic homo of h2o2 and the bosonic lumo of hocl producing the intermediate singlet multiplicity chloroperoxy acid ( hoocl ) and singlet multiplicity h2o .
disintegration of the chloroperoxy intermediate yields ground state singlet multiplicity chloride and electronically excited singlet multiplicity oxygen .
the net reaction is h2o2 + hocl o2 + h2o + cl + h. the bosonic orbital symmetry of o2 allows direct constructive spin - allowed overlap with the bosonic frontier orbitals of biological substrates producing singlet multiplicity dioxygenated products of bosonic symmetry . in conventional combustive burning , sufficient energy must be applied to a nonradical ( singlet ) substrate to produce homolytic bond cleavage yielding two radical ( doublet ) products .
the fermionic somo of these doublet multiplicity radical products can now constructively overlap with one of the fermionic somos of triplet multiplicity ground state o2 . as described in table 1 , the product of doublet - triplet reaction will have doublet multiplicity .
such radical - diradical reactions yield heat plus additional radical products that can further participate in the radical propagation process of burning .
neutrophil microbicidal action is combustion by a different pathway . instead of radicalizing a substrate to facilitate reaction with diradical o2 ,
the bifermionic orbitals of ground state triplet o2 are converted to the bosonic orbitals of o2 . in its
electronically excited singlet multiplicity state , the bosonic frontier orbitals of oxygen can participate in spin - allowed electrophilic oxygenation reactions with a broad spectrum of singlet multiplicity biological molecules . as per spin conservation ,
such products are nonradical , diamagnetic , and unable to participate in the radical propagation reactions that are characteristic of burning .
the microsecond lifetime range of o2 confines reactions to within about a 0.2  m radius from its point of origin [ 27 , 28 ] .
thus , phagolysosomal generation of o2 in close proximity to the target microbe guarantees that combustive action is focused on the microbe with minimal collateral damage to the host . by changing the spin quantum number of oxygen , the neutrophil not only realizes its potent electrophilic microbicidal action , but also limits such combustive action to the target microbe .
one carbonyl is in the ground singlet multiplicity state , and the other carbonyl is in the electronically excited n singlet multiplicity state .
as depicted in figure 6 , the n description indicates that an electron from the ground state nonbonding ( n ) orbital of the atomic oxygen ( o ) component occupies the  orbital of the electronically excited carbonyl function . when the spin of the excited  electron is antisymmetric to that of the ground state n electron of o , the electronically excited carbonyl is singlet multiplicity .
thus , -to - n relaxation to ground state is spin - allowed and yields a photon with energy proportional to the difference between the two orbital states . in bioluminescence and chemiluminescence processes ,
dioxygenated products disintegrate by oxygen - oxygen bond cleavage producing the singlet multiplicity n electronically excited carbonyl .
, electronic excitation to the n state can occur when a photon of proper energy is captured by an electron in the nonbonding ( n ) orbital of the o component of the carbonyl . as depicted in figure 6 , relaxation of the electron from  of the singlet
excited carbonyl back to the n orbital of o results in photon ( h ) emission and returns the carbonyl function to its ground singlet state .
the frequency of the emitted photon is the energy difference that separates the n orbital from the  orbital .
photons are symmetric bosons ; their absorbance or emission does not affect the electron spin .
in fluorescence , photon capture promotes an electron of an orbital to an appropriately higher energy orbital .
such photon excitation results in transient antibonding and fermionic character , but the overall spin symmetry is retained ; that is , singlet character is retained .
relaxation of an n electronically excited singlet multiplicity carbonyl to its singlet ground state by fluorescence or chemiluminescence is spin - allowed , and , as such , the lifetime of the excited state is very short - lived , typically in the nanosecond range .
the chemiluminescence produced by neutrophils is an energy byproduct of microbicidal combustion and varies with the molecular composition of the microbe .
different microbes present substrates that vary with regard to dioxygenation susceptibility and combustion quantum efficiencies , that is , the photon yield per dioxygenation reaction .
native luminescence is easily measured using a luminometer , but the photon yield is insufficient for measurement of less than a hundred thousand neutrophils . in order to increase photon yield and impose reaction specificity ,
chemiluminigenic substrates are susceptible to dioxygenation producing endoperoxides or dioxetanes ultimately yielding n electronically excited carbonyl products .
in addition to increasing sensitivity , chemiluminigenic substrates can be selected for specificity with regard to the type of oxygenation activity measured .
the sensitivity and specificity obtained using selective chemiluminigenic probe in combination with phagocytic and chemical stimuli allow simultaneous quantification of multiple neutrophil metrics using a microliter or less of unseparated whole blood . when subjected to discriminant function analysis , such neutrophil luminescence measurements allow assessment of host inflammatory state and hematopoietic marrow stress [ 3235 ] .
neutrophil leukocytes respond to cytokines and other agents by fusing specific granules with the cytoplasmic membrane , that is , specific degranulation .
such fusion effectively increases the surface - to - volume ratio of the neutrophil , as is required for locomotion and phagocytosis , and for upregulated membrane expression of cytokine and opsonin receptors , as is required for effective recognition and phagocytosis .
microbicidal effectiveness is optimized by coordinating phagocytosis with activation of nadph oxidase , resulting in dynamic acidification and h2o2 production .
fusion of the lysosomal azurophilic granules with the microbe - containing phagosome produces a phagolysosome with a relatively high mpo concentration in an acidic milieu replete with h2o2 .
the neutrophils of patients with chronic granulomatous disease ( cgd ) have defective nadph oxidase function and consequently have defective microbicidal combustion and do not chemiluminesce . these cgd neutrophils phagocytose microbes and release mpo into the phagolysosomal space , but the neutrophil respiratory burst is defective and microbicidal action is poor . consequently , cgd patients have an increased susceptibility to infection .
interestingly , the incidence of pneumococcal and other streptococcal infections is not increased in cgd patients ; that is , infection rates for these microbes are about equivalent to those for healthy subjects .
pneumococci and streptococci are cytochrome - deficient lactic acid bacteria ( lab ) that produce lactic acid and h2o2 as metabolic products [ 38 , 39 ] .
phagocytosis of live lab by cgd neutrophils does result in microbicidal action . in the case of cgd neutrophils ,
the phagocytosed lab provides the acid and h2o2 necessary for effective mpo - mediated microbicidal combustion and chemiluminescence .
human neutrophils contain a relatively high concentration of mpo ( about 5% of the dry weight of the neutrophil ) in their azurophilic granules .
following departure of the neutrophil leukocyte from the hematopoietic marrow and a relatively short transit time in the circulating blood , the neutrophil leaves the circulating and enters the tissue pool .
however , even in the absence of inflammation and infection , healthy humans have significant concentrations of neutrophils present in tissue fluids .
the oral and vaginal cavities have neutrophil concentrations in proportion to blood neutrophil concentrations [ 41 , 42 ] .
when neutrophils transit from the blood to tissue and body spaces , they carry mpo into these spaces .
the oral and vaginal cavities have acidic ph . the normal florae of these spaces are cytochrome - negative lab that generate lactic acid and h2o2 as metabolic products .
the transit of neutrophils into such spaces delivers mpo into milieux that are rich in lab .
however , lab show relatively poor mpo binding . when small concentrations of neutrophil - free mpo are added to bacterial suspensions containing viridans streptococci with other competing bacteria , a potent synergistic microbicidal action is directed against mpo - binding gram - positive , for example , staphylococcus aureus , and gram - negative , for example , pseudomonas aeruginosa and escherichia coli , microbes .
this lab - mpo synergistic action may explain the dominance of streptococci and lactobacilli in healthy oral and vaginal cavities .
selective binding of mpo to a microbe guarantees that o2 is generated in close proximity to the target microbe , resulting in selective , focused combustive microbicidal action .
the o2 lifetime of a few microseconds limits damage to within about a 0.2  m radius of its point of generation [ 27 , 28 ] .
thus , combustion is focused on potential pathogens with minimal collateral damage to the host cells and the normal lab flora .
these rules forbid the direct reaction of triplet oxygen with singlet organic molecules , and , as such , combustion is not spontaneous .
chemical reactions involve frontier orbitals . changing the multiplicity of oxygen changes its frontier orbitals , eliminating the symmetry barrier to its electrophilic reactive potential .
the redox reactions of neutrophil respiratory burst metabolism change triplet ground state ( diradical ) o2 to singlet electronically excited ( nonradical ) o2 .
in addition , other singlet multiplicity ( nonradical ) microbicidal reactants , for example , h2o2 and hocl , are generated .
o2 has one empty ( lumo )  orbital and one full ( homo )  orbital with bosonic character .
this highly electrophilic lumo can participate in spin - allowed bosonic lumo - homo reactions with biological molecules .
the dioxygenated products of such combustions yield the electronically excited carbonyl functions that relax by photon emission , that is , luminescence or chemiluminescence . considering frontier orbital reactivity in the bosonic - fermionic terms of particle physics
broadens the perspective for explaining oxygen chemistry in particular and for appreciating reaction chemistry in general .
radical reactions involving singly occupied atomic or molecular orbitals ( so(a)mo ) are uncommon in biology under normal conditions , that is , in the absence of high energy radiation or heat producing homolytic bond cleavage .
biological reactions involving one electron transfer are typically restricted to flavoenzymes and to highly ordered cytochrome electron transport systems such as those found in mitochondria .
chemical reactions can be generalized as constructive bosonic transfers ( i.e. , homo - lumo ) or constructive fermionic annihilations .
radical - radical ( i.e. , so(a)mo - so(a)mo ) orbital overlap is typically constructive ; that is , fermionic radicals react with fermionic radicals .
overlap of a bosonic homo with a fermionic so(a)mo is not constructive . as illustrated in figure 1 ,
the first steps of the hexose monophosphate metabolic pathway involve dehydrogenation of glucose-6-phosphate and reduction of nadp yielding nadph ; these redox reactions involve balanced two equivalent bosonic transfers .
the bosonic nature of the antisymmetric orbital electron - couple may be essential for such biologic redox transfer .
there are advantages to transferring electrons as a bosonic orbital - couple . as stated by dirac ,
 if a state has zero total angular momentum , the dynamical system is equally likely to have any orientation , and hence spherical symmetry occurs  .
this has significance with regard to the heisenberg uncertainty principle which states that the uncertainty of momentum ( p ) multiplied by the uncertainty of position ( x ) is always equal to or greater than ( 1/2) ; that is , px  ( 1/2) . the spin momentum of the bosonic orbital electron - couple is known , that is , zero .
thus , the intermolecular redox transfer of a bosonic orbital electron - couple may proceed by a quantum tunneling mechanism analogous to the emission of a bosonic alpha particle from an atomic nucleus in alpha radiation decay .
such a quantum tunneling mechanism explains the facility for electron - couple transfer in biologic redox reactions .
 neutrophil leukocytes protect against a varied and complex array of microbes by providing microbicidal action that is simple , potent , and focused . 
 neutrophils provide such action via redox reactions that change the frontier orbitals of oxygen ( o2 ) facilitating combustion . 
 the spin conservation rules define the symmetry barrier that prevents direct reaction of diradical o2 with nonradical molecules , explaining why combustion is not spontaneous . in burning , 
 the spin barrier is overcome when energy causes homolytic bond cleavage producing radicals capable of reacting with diradical o2 to yield oxygenated radical products that further participate in reactive propagation . 
 neutrophil mediated combustion is by a different pathway . 
 changing the spin quantum state of o2 removes the symmetry restriction to reaction . 
 electronically excited singlet molecular oxygen ( 1o2 * ) is a potent electrophilic reactant with a finite lifetime that restricts its radius of reactivity and focuses combustive action on the target microbe . 
 the resulting exergonic dioxygenation reactions produce electronically excited carbonyls that relax by light emission , that is , chemiluminescence . 
 this overview of neutrophil combustive microbicidal action takes the perspectives of spin conservation and bosonic - fermionic frontier orbital considerations . 
 the necessary principles of particle physics and quantum mechanics are developed and integrated into a fundamental explanation of neutrophil microbicidal metabolism . 