S1

ELECRONIC SUPPLEMENTARY INFORMATION

Analysis of the Antioxidant Activity of 4-( 5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic Acid Derivatives using Quantum-Chemistry Descriptors and Molecular Docking

Ahmed Taki Eddine Ardjania and Sidi Mohamed Mekelleche*a

aLaboratory of Applied Thermodynamics and Molecular Modelling, Department of Chemistry,

Faculty of Science, University of Tlemcen, PB 119, Tlemcen, 13000, Algeria.

*

PagesContents

S2 Figure 1S:Atom-by-atom superposition of the docked structures of HPA: The

experimental structure (in green)[1] and the calculated structure (in white).

S3-15 Cartesian coordinates of the optimized structures (neutral, radical, cationic radical and

anionic forms)of compounds A-E at the B3LYP/6-31G++(2d,2p) level in vacuum.

S16 Table 1S: Some selected geometrical parameters of compound Acalculatedat the

B3LYP/6-31++G(2d, 2p) in gas phase, EtOH, DMSO, and water.

S17Table 2S: Calculated (B3LYP/6-311G++(2d,2p) values of BDE (in kcal/mol) for compounds A-E in gas-phase for OH, NH and CH bonds.

S18Table 3S: The enthalpy values (kcal/mol) of hydrogen atom, proton, electron and solvation corrections in vacuum and polar media (EtOH, DMSO, and water).

S19Figure 2S: The RB3LYP/6-311++G(2d,2p) atomic orbital compositions of the frontier molecular orbital for compound A-E in vacuum. The calculations for canonical MOs

wereaccomplished with isovalue 0.02

S20-21The total atomic spin densities for the phenoxy radicals A-E in EtOH (Figure 3S)and in DMSO (Figure 3S) calculated at the ROB3LYP/6-311++G(2d,2p) level

S22References of the ESI

Figure1S: Atom-by-atom superposition of the docked structures of HPA: The experimental

structure (in green)[1] and the calculated structure (in white).

Note:

For the validation of the docking technique, the reference system (HPA) was docked in their native protein structure. The superimposition of the docked and experimental structures of HPAshows that the docking model recapitulates the orientation of the native ligand in the active site, and the same interactions with the key amino acids (Arg880 and Thr1010) of the binding cavity are formed with a ligand.

Compound A (neutral)

Enthalpy= -1201.8239a.u.

O 4.03410200 -0.90772800 0.00000000

H 3.04119900 -0.87759300 0.00000000

C 4.55393000 0.31163500 0.00000000

O 5.74839900 0.50307600 0.00000000

C 3.65149900 1.51743600 0.00000000

H 4.24870900 2.41941100 0.00000000

C 2.32101700 1.67684300 0.00000000

H 1.96395400 2.70047200 0.00000000

C 1.25772900 0.64318900 0.00000000

O 1.46799900 -0.57239800 0.00000000

N 0.00000000 1.16851300 0.00000000

H -0.07504900 2.17342900 0.00000000

C -1.24016600 0.50727100 0.00000000

C -1.40291500 -0.87796300 0.00000000

H -0.54031300 -1.51939600 0.00000000

C -2.68562800 -1.40968700 0.00000000

C -3.81020700 -0.60073500 0.00000000

H -4.79780500 -1.03493800 0.00000000

C -3.64604300 0.78060000 0.00000000

H -4.51416000 1.42741100 0.00000000

C -2.37737500 1.33364700 0.00000000

O -2.14273500 2.68732600 0.00000000

H -2.97367200 3.17065400 0.00000000

Cl -2.87917800 -3.15380300 0.00000000

Compound A (anion)

Enthalpy= -1201.3261a.u.

O 4.04644100 -0.81896000 0.00000000

H 3.03012200 -0.80092600 0.00000000

C 4.54508300 0.40656400 0.00000000

O 5.74662500 0.61032900 0.00000000

C 3.62133200 1.58335300 0.00000000

H 4.18503200 2.50655100 0.00000000

C 2.28001500 1.68622700 0.00000000

H 1.87889100 2.69332200 0.00000000

C 1.25584500 0.62285100 0.00000000

O 1.52738600 -0.60155300 0.00000000

N 0.00000000 1.09333300 0.00000000

H -0.17884900 2.10254600 0.00000000

C -1.23593400 0.45020200 0.00000000

C -1.44883500 -0.92522300 0.00000000

H -0.61260500 -1.60419900 0.00000000

C -2.75578400 -1.38581900 0.00000000

C -3.83782700 -0.50624300 0.00000000

H -4.84438000 -0.90187600 0.00000000

C -3.62797100 0.86187000 0.00000000

H -4.46717300 1.54453100 0.00000000

C -2.31704900 1.42273700 0.00000000

O -2.04857100 2.66548900 0.00000000

Cl -3.06113800 -3.13734300 0.00000000

Compound A (cation)

Enthalpy= -1201.5231a.u.

O 4.05752900 -1.04976000 0.00000000

H 3.08115900 -1.03204400 0.00000000

C 4.58265300 0.17141700 0.00000000

O 5.77034300 0.36281500 0.00000000

C 3.69400200 1.39451800 0.00000000

H 4.31273600 2.28244800 0.00000000

C 2.36400100 1.59679400 0.00000000

H 2.03584500 2.62938700 0.00000000

C 1.29512300 0.59320600 0.00000000

O 1.41843300 -0.61692500 0.00000000

N 0.00000000 1.17345800 0.00000000

H -0.03602500 2.18382700 0.00000000

C -1.20644200 0.54381900 0.00000000

C -1.40069400 -0.84237600 0.00000000

H -0.55463100 -1.50539900 0.00000000

C -2.68896700 -1.33773800 0.00000000

C -3.83316000 -0.48199400 0.00000000

H -4.81985700 -0.92035200 0.00000000

C -3.66782000 0.87776300 0.00000000

H -4.52339300 1.53943900 0.00000000

C -2.37435700 1.41034900 0.00000000

O -2.11237100 2.71199100 0.00000000

H -2.91017400 3.25968800 0.00000000

Cl -2.95548000 -3.02768900 0.00000000

Compound A (radical)

Enthalpy= -1201.2039a.u.

O 4.02976800 -0.94476200 0.00000000

H 3.03969300 -0.91260200 0.00000000

C 4.55497500 0.27354500 0.00000000

O 5.74954600 0.45884100 0.00000000

C 3.65860900 1.48414000 0.00000000

C 2.32831300 1.65176600 0.00000000

C 1.26386300 0.62479800 0.00000000

O 1.45484800 -0.59207600 0.00000000

N 0.00000000 1.15428500 0.00000000

H -0.11623200 2.16367300 0.00000000

C -1.21837100 0.51028600 0.00000000

C -1.42691900 -0.85760800 0.00000000

C -2.73941300 -1.32696600 0.00000000

C -3.86146900 -0.46811500 0.00000000

H -4.85229700 -0.89686900 0.00000000

C -3.67657900 0.88367200 0.00000000

H -4.50920900 1.57174500 0.00000000

C -2.35209600 1.45315300 0.00000000

O -2.13151300 2.67988800 0.00000000

Cl -3.01203200 -3.04166500 0.00000000

H -0.59810700 -1.54331200 0.00000000

H 1.97350000 2.67561800 0.00000000

H 4.26053000 2.38290700 0.00000000

Compound B (neutral)

Enthalpy= -1315.1834a.u.

O 4.49302100 1.27225500 0.00041400

H 3.50287000 1.21376100 0.00039700

C 5.04858200 0.06819000 0.00042600

O 6.24770900 -0.08771400 0.00030900

C 4.18269500 -1.16445700 0.00005700

H 4.80732400 -2.04764000 0.00015400

C 2.85778900 -1.36551000 -0.00035400

H 2.53152600 -2.39923600 -0.00045600

C 1.76460200 -0.36536800 -0.00072700

O 1.93307600 0.85636800 -0.00038000

N 0.52101900 -0.92667300 -0.00046400

H 0.46560700 -1.93389400 -0.00037300

C -0.73128100 -0.29578000 -0.00024100

C -0.93837100 1.08027300 -0.00026200

H -0.09365900 1.74609300 -0.00047200

C -2.23884700 1.58848100 0.00000300

C -3.33570200 0.75688600 0.00026400

C -3.14330800 -0.63342300 0.00027400

C -1.84277900 -1.16228200 0.00004400

O -1.60445500 -2.48537800 0.00015300

H -2.48236200 -2.94086500 0.00052100

Cl -2.46221000 3.32683100 -0.00002500

H -4.33746600 1.16138000 0.00044300

C -4.28453200 -1.53613000 0.00048800

H -5.28064000 -1.06696700 0.00037000

O -4.18633200 -2.75894700 -0.00008700

Compound B (anion)

Enthalpy= -1314.6814a.u.

O -4.50131500 1.27136900 -0.00008900

H -3.49094000 1.20523500 -0.00001500

C -5.05778600 0.07091400 -0.00008700

O -6.26579500 -0.07717200 -0.00015400

C -4.19051300 -1.15093300 -0.00002400

H -4.80019400 -2.04444200 -0.00007500

C -2.85810500 -1.32190700 0.00009200

H -2.50720600 -2.34747600 0.00010800

C -1.78064500 -0.30803300 0.00020400

O -1.98973000 0.92502600 0.00008700

N -0.54876500 -0.84038900 0.00014300

H -0.41380300 -1.85669200 0.00011500

C 0.71270400 -0.24836400 0.00008100

C 0.97857900 1.10418600 0.00007300

H 0.17269600 1.81897700 0.00011900

C 2.31514900 1.51829400 0.00000100

C 3.34543000 0.60849900 -0.00005600

C 3.11105000 -0.77893400 -0.00004700

C 1.75671800 -1.28332200 0.00002000

O 1.40439700 -2.48722200 0.00004900

Cl 2.67027000 3.25756600 -0.00001200

H 4.37004300 0.95812100 -0.00010700

C 4.29508700 -1.62833700 -0.00010600

H 5.23804100 -1.03134300 -0.00014600

O 4.36645600 -2.84333300 -0.00010600

Compound B (cation)

Enthalpy= -1314.8765a.u.

O 4.55741000 1.27303300 0.00073800

H 3.58142600 1.26090200 0.00092800

C 5.07587600 0.04872900 0.00042800

O 6.26239600 -0.14893100 0.00015100

C 4.18061500 -1.16949300 -0.00006000

H 4.79433300 -2.06095400 -0.00009300

C 2.84921500 -1.36486800 -0.00041100

H 2.51528900 -2.39558300 -0.00057600

C 1.78623500 -0.35641400 -0.00064700

O 1.91230900 0.85388500 -0.00045400

N 0.48748200 -0.92807400 -0.00040400

H 0.43650900 -1.93917000 -0.00032600

C -0.71167200 -0.28974300 -0.00023200

C -0.90815200 1.09799800 -0.00024700

H -0.05996400 1.75950800 -0.00041100

C -2.19526300 1.60557000 -0.00003800

C -3.34097500 0.76110600 0.00018200

C -3.18708600 -0.60564300 0.00018700

C -1.87706500 -1.15614900 0.00000000

O -1.67557900 -2.44353000 0.00007400

H -2.58786600 -2.89456900 0.00037800

Cl -2.44505000 3.29951900 -0.00004700

H -4.32682100 1.20566300 0.00032300

C -4.33157800 -1.53195200 0.00034100

H -5.34044900 -1.10029500 0.00056500

O -4.16901900 -2.74266300 0.00021900

Compound B (radical)

Enthalpy= -1314.5423a.u.

O -0.51476200 -4.66949700 0.00000000

H -0.18894900 -3.73534500 0.00000000

C -1.84085000 -4.72232800 0.00000000

O -2.44256500 -5.77019700 0.00000000

C -2.65026600 -3.45125000 0.00000000

C -2.33192200 -2.14855100 0.00000000

C -0.99282200 -1.52317900 0.00000000

O 0.07568600 -2.13391800 0.00000000

N -1.03490800 -0.15005000 0.00000000

H -1.93562000 0.32246900 0.00000000

C 0.00000000 0.75374000 0.00000000

C 1.35000400 0.45240900 0.00000000

C 2.26179300 1.50558200 0.00000000

C 1.85871600 2.85457500 0.00000000

H 2.61533600 3.62772600 0.00000000

C 0.53035600 3.20171600 0.00000000

C -0.48931800 2.15674800 0.00000000

O -1.70884600 2.35618600 0.00000000

Cl 3.95899600 1.14780000 0.00000000

H 1.68794600 -0.56899700 0.00000000

H -3.16083300 -1.45085300 0.00000000

H -3.70482100 -3.69210200 0.00000000

C 0.20537900 4.65061700 0.00000000

H 1.11075500 5.29215100 0.00000000

O -0.89561400 5.13770400 0.00000000

Compound C (neutral)

Enthalpy= -1241.1247a.u.

O 0.72760300 -4.40089900 0.00000000

H 0.37229300 -3.47282300 0.00000000

C 2.05310600 -4.41010600 0.00000000

O 2.69051900 -5.43846300 0.00000000

C 2.81742000 -3.11250800 0.00000000

H 3.87998300 -3.31542800 0.00000000

C 2.45093300 -1.82364300 0.00000000

H 3.25747300 -1.09920700 0.00000000

C 1.08685900 -1.24128900 0.00000000

O 0.04686100 -1.90527600 0.00000000

N 1.08729900 0.12117100 0.00000000

H 1.98586800 0.57720900 0.00000000

C 0.00000000 1.01253300 0.00000000

C -1.34047800 0.62775500 0.00000000

H -1.60404200 -0.41418700 0.00000000

C -2.31389300 1.61475100 0.00000000

C -1.99133500 2.96208600 0.00000000

H -2.77535800 3.70453300 0.00000000

C -0.65534300 3.36245000 0.00000000

C 0.32872800 2.37782400 0.00000000

O 1.67286500 2.67092300 0.00000000

H 1.80811700 3.62237600 0.00000000

Cl -4.00408000 1.13915900 0.00000000

C -0.27426900 4.82096900 0.00000000

H 0.31105000 5.08931400 0.88412200

H 0.31105000 5.08931400 -0.88412200

H -1.16132300 5.44978300 0.00000000

Compound C (anion)

Enthalpy= -1240.6271a.u.

O -4.20288800 1.46541800 0.00023800

H -3.19611400 1.32370100 0.00007300

C -4.84711000 0.30976200 0.00041000

O -6.06466300 0.25413700 0.00066500

C -4.07387800 -0.97077100 0.00020800

H -4.74605400 -1.81826400 0.00034300

C -2.75489800 -1.23612100 -0.00008100

H -2.47920600 -2.28456200 -0.00012300

C -1.60904500 -0.30557100 -0.00036300

O -1.72934900 0.94292300 -0.00015800

N -0.41991600 -0.92617300 -0.00026300

H -0.36733500 -1.94919400 -0.00018100

C 0.88567000 -0.43812700 -0.00019100

C 1.26242600 0.90349800 -0.00021800

H 0.51648600 1.68016600 -0.00030700

C 2.61464600 1.19138000 -0.00011700

C 3.58057500 0.18291800 -0.00000100

C 3.22196100 -1.15536200 0.00001800

C 1.83811000 -1.52882300 -0.00007500

O 1.42563200 -2.73411800 -0.00007000

Cl 3.14431600 2.88889800 -0.00013700

C 4.24637300 -2.25434300 0.00014000

H 4.12584000 -2.90168500 0.87220200

H 4.12589200 -2.90182200 -0.87182500

H 5.25996900 -1.85108500 0.00014200

H 4.62772600 0.45717300 0.00007000

Compound C (cation)

Enthalpy=-1240.8289a.u.

O 0.77077600 -4.45206400 0.00000000

H 0.37729900 -3.55773000 0.00000000

C 2.09957500 -4.41578700 0.00000000

O 2.77182300 -5.41373800 0.00000000

C 2.83570000 -3.09558800 0.00000000

H 3.90145900 -3.28346700 0.00000000

C 2.45951500 -1.80456700 0.00000000

H 3.25844100 -1.07268600 0.00000000

C 1.09875700 -1.25537000 0.00000000

O 0.05348700 -1.87905200 0.00000000

N 1.08116400 0.16009500 0.00000000

H 1.98221100 0.61751900 0.00000000

C 0.00000000 0.99069700 0.00000000

C -1.33546500 0.58539000 0.00000000

H -1.58843000 -0.45911200 0.00000000

C -2.31615900 1.55831500 0.00000000

C -2.01616700 2.95359800 0.00000000

H -2.83449300 3.65864800 0.00000000

C -0.71777500 3.39726900 0.00000000

C 0.29606300 2.41307400 0.00000000

O 1.58877000 2.71671500 0.00000000

H 1.74540400 3.67195700 0.00000000

Cl -3.96518200 1.10017700 0.00000000

C -0.35232600 4.85618200 0.00000000

H 0.22708800 5.12595100 0.88673700

H 0.22708800 5.12595100 -0.88673700

H -1.24529000 5.47514000 0.00000000

Compound C (radical)

Enthalpy= -1240.5081a.u.

O 0.69556400 -4.41105100 0.00000000

H 0.34171000 -3.48518000 0.00000000

C 2.02212100 -4.42314800 0.00000000

O 2.65588900 -5.45283700 0.00000000

C 2.79057300 -3.12779400 0.00000000

C 2.42899600 -1.83674700 0.00000000

C 1.06932900 -1.25339100 0.00000000

O 0.02213000 -1.90305800 0.00000000

N 1.06769600 0.11540500 0.00000000

H 1.95271300 0.61396100 0.00000000

C 0.00000000 0.98977200 0.00000000

C -1.33878300 0.65069500 0.00000000

C -2.27286300 1.68644500 0.00000000

C -1.91420800 3.04910200 0.00000000

H -2.69724300 3.79341700 0.00000000

C -0.59642900 3.42668300 0.00000000

C 0.43121300 2.39778400 0.00000000

O 1.64936600 2.66337000 0.00000000

Cl -3.96247700 1.27966600 0.00000000

H -1.65334900 -0.37778400 0.00000000

H 3.23516800 -1.11266000 0.00000000

H 3.85240800 -3.33419400 0.00000000

C -0.15901100 4.85721700 0.00000000

H 0.46061600 5.06956700 0.87240200

H 0.46061600 5.06956700 -0.87240200

H -1.01361400 5.53005200 0.00000000

Compound D (neutral)

Enthalpy= -1319.7144a.u.

O -4.94030000 1.13920000 0.08600000

H -3.94650000 1.12000000 0.06890000

C -5.44700000 -0.08410000 0.02940000

O -6.63960000 -0.28890000 0.03940000

C -4.53210000 -1.27740000 -0.05120000

H -5.11940000 -2.18500000 -0.09100000

C -3.20010000 -1.42060000 -0.08110000

H -2.83210000 -2.43850000 -0.14270000

C -2.14790000 -0.37610000 -0.04090000

O -2.37360000 0.83520000 0.03010000

N -0.88600000 -0.88600000 -0.08950000

H -0.80020000 -1.88830000 -0.14740000

C 0.34890000 -0.21320000 -0.07150000

C 0.49140000 1.17090000 0.00520000

H -0.37570000 1.80360000 0.05590000

C 1.77140000 1.70100000 0.01100000

C 2.89870000 0.89990000 -0.05840000

C 2.77800000 -0.48910000 -0.13140000

C 1.49140000 -1.02960000 -0.13440000

O 1.24110000 -2.38190000 -0.19260000

H 2.06180000 -2.86930000 -0.30510000

Cl 1.96600000 3.44460000 0.10440000

H 3.87230000 1.36260000 -0.05760000

C 3.99570000 -1.40380000 -0.16490000

H 3.75490000 -2.25740000 -0.81250000

C 5.23900000 -0.75570000 -0.78570000

H 5.02870000 -0.34710000 -1.77350000

H 5.62670000 0.04830000 -0.15980000

H 6.03170000 -1.49690000 -0.88650000

C 4.31080000 -1.95250000 1.24120000

H 3.45000000 -2.44860000 1.69060000

H 5.13270000 -2.66840000 1.20030000

H 4.60300000 -1.13890000 1.90570000

Compound D (anion)

Enthalpy= -1319.2184a.u.

O -4.93618400 1.11652800 0.07993200

H -3.91992100 1.10319900 0.06636100

C -5.42983200 -0.10944000 0.01916900

O -6.63035700 -0.31884300 0.02464500

C -4.50148100 -1.28012700 -0.05930400

H -5.06175200 -2.20433000 -0.10412900

C -3.15998600 -1.37670400 -0.08300500

H -2.75505500 -2.38033100 -0.14571900

C -2.13992000 -0.31005800 -0.03613500

O -2.41652500 0.91070900 0.03871800

N -0.88255800 -0.77459400 -0.08150100

H -0.70169400 -1.78095500 -0.14262300

C 0.35152300 -0.12597900 -0.06341000

C 0.55565800 1.24937500 0.01585600

H -0.28145700 1.92441000 0.07114800

C 1.86092100 1.70403400 0.01815100

C 2.94624600 0.83012500 -0.05794200

C 2.76376800 -0.54246300 -0.13421500

C 1.43380600 -1.08481100 -0.13653100

O 1.16860800 -2.33046000 -0.20062500

Cl 2.17181700 3.45279500 0.11367700

H 3.94287400 1.24738400 -0.05952300

C 3.91200800 -1.53207400 -0.19648700

H 3.58533000 -2.32223100 -0.87773300

C 5.22296100 -0.94824500 -0.73340000

H 5.08320200 -0.47746000 -1.70770900

H 5.64221700 -0.19886700 -0.05797800

H 5.97027900 -1.73720700 -0.84270700

C 4.13412200 -2.20155200 1.17306600

H 3.20916900 -2.65629100 1.52286700

H 4.89774400 -2.98193900 1.10747000

H 4.46298200 -1.46669100 1.91204200

Compound D (cation)

Enthalpy= -1319.4209a.u.

O 5.00247300 1.14690800 0.08457000

H 4.03548300 1.17952100 -0.05247700

C 5.45690800 -0.10142400 0.13138100

O 6.60271400 -0.36187400 0.39039500

C 4.53846100 -1.26704700 -0.15205700

H 5.12603700 -2.17103200 -0.24483900

C 3.20506800 -1.40973600 -0.24555000

H 2.83872800 -2.41702600 -0.40438800

C 2.17540600 -0.36650400 -0.16446500

O 2.35513500 0.83559200 -0.08941900

N 0.86311300 -0.88963200 -0.19172400

H 0.78398400 -1.89528600 -0.24772700

C -0.31847800 -0.20955400 -0.13021900

C -0.45093000 1.17512100 -0.04191400

H 0.41727200 1.80759600 -0.01328300

C -1.72585200 1.70536500 0.00453800

C -2.89998400 0.89723500 -0.03463300

C -2.82294500 -0.47107000 -0.11147300

C -1.52087900 -1.02706600 -0.16120800

O -1.29538200 -2.33293100 -0.24499200

H -2.11718000 -2.84414500 -0.27882900

Cl -1.93176000 3.40240100 0.10990200

H -3.85778800 1.39260500 -0.00452800

C -4.04142700 -1.38093500 -0.11433000

H -3.83379300 -2.20606000 -0.80885100

C -5.30822600 -0.69786900 -0.64215700

H -5.65871800 0.07970100 0.03690300

H -5.15316900 -0.25757800 -1.62650800

H -6.10739900 -1.43187800 -0.72596500

C -4.27847900 -1.97652400 1.29133700

H -5.09700800 -2.69366800 1.25728900

H -3.40199300 -2.48830800 1.69192700

H -4.54770800 -1.18934100 1.99508700

Compound D (radical)

Enthalpy= -1319.0988a.u.

O -4.95526200 1.12912200 0.09138600

H -3.96409700 1.12343600 0.07415500

C -5.44855900 -0.10070200 0.02861300

O -6.63806600 -0.31762200 0.03802700

C -4.52127300 -1.28427900 -0.05796700

C -3.18728500 -1.41482100 -0.08808700

C -2.14964200 -0.36099000 -0.04224800

O -2.37497100 0.84836900 0.03339600

N -0.87443100 -0.85488600 -0.09222200

H -0.73155000 -1.85859300 -0.15588500

C 0.32882900 -0.17874500 -0.07060800

C 0.49807800 1.18881900 0.01012900

C 1.80262500 1.68043800 0.01256300

C 2.94120900 0.85452100 -0.06184000

H 3.91251000 1.32433300 -0.05992100

C 2.82073600 -0.50973900 -0.13670700

C 1.48373000 -1.09019500 -0.14790300

O 1.27766600 -2.31810000 -0.22434500

Cl 2.03876300 3.40044900 0.10997600

H -0.34533200 1.85360700 0.06675800

H -2.80572200 -2.42684200 -0.15493400

H -5.09933900 -2.19747600 -0.10285000

C 3.99756400 -1.45727000 -0.18207000

H 3.69912500 -2.27916700 -0.83555500

C 5.27692800 -0.82976900 -0.74360600

H 5.11313500 -0.38808400 -1.72685500

H 5.67636200 -0.05645300 -0.08524600

H 6.04740500 -1.59388700 -0.84410300

C 4.24666900 -2.06457200 1.21480300

H 3.35569100 -2.56158400 1.59354400

H 5.04869100 -2.80155200 1.16283200

H 4.54257800 -1.29152000 1.92588500

Compound E (neutral)

Enthalpy= -1359.0043a.u.

O -5.20593900 1.01264400 -0.00058300

H -4.21233500 1.04417700 -0.00103000

C -5.64864800 -0.23660200 0.00053500

O -6.82932200 -0.50178500 0.00256800

C -4.67310900 -1.38361600 -0.00090200

H -5.21286300 -2.32106900 -0.00138000

C -3.33530800 -1.45940400 -0.00109900

H -2.91547100 -2.45886600 -0.00176300

C -2.33761500 -0.36170700 -0.00067300

O -2.62649000 0.83845300 -0.00071600

N -1.05179800 -0.80954400 -0.00033800

H -0.91601700 -1.80784500 -0.00029600

C 0.14948000 -0.07753900 -0.00017100

C 0.21537600 1.31290000 -0.00010500

H -0.68407600 1.90091400 -0.00017800

C 1.46684300 1.90157100 0.00000200

C 2.63074700 1.15240700 0.00007000

C 2.59794100 -0.24672500 0.00008500

C 1.33075300 -0.84449600 -0.00004000

O 1.10779200 -2.20351600 0.00003100

H 1.93688200 -2.68499500 -0.00085000

Cl 1.58147400 3.65527800 0.00004300

H 3.57172300 1.67416400 0.00014600

C 3.90526400 -1.07004100 0.00025400

C 3.99922400 -1.94346700 -1.27508000

H 4.93186200 -2.50858300 -1.27000800

H 3.18861500 -2.66404500 -1.38880100

H 3.98832000 -1.31635700 -2.16625500

C 5.14983600 -0.16204200 0.00027100

H 5.19101000 0.47318300 -0.88406200

H 5.19076500 0.47344000 0.88442900

H 6.04489700 -0.78373500 0.00048700

C 3.99892400 -1.94320600 1.27578000

H 3.18801700 -2.66340600 1.38961200

H 4.93138300 -2.50862500 1.27084600

H 3.98823200 -1.31584700 2.16678000

Compound E (anion)

Enthalpy= -1358.5118a.u.

O -5.18901200 0.99560300 -0.00041400

H -4.17359400 1.03282800 -0.00041800

C -5.62022100 -0.25519700 -0.00042700

O -6.80870700 -0.52416100 -0.00049200

C -4.63410800 -1.38075400 -0.00030200

H -5.14790200 -2.33263800 -0.00030900

C -3.28954700 -1.41205800 -0.00020900

H -2.83527600 -2.39627500 -0.00015500

C -2.32318700 -0.29502700 -0.00014900

O -2.66092400 0.91232700 -0.00014800

N -1.04446800 -0.69882900 -0.00007500

H -0.81018700 -1.69679800 -0.00006800

C 0.15582500 0.01085400 0.00001000

C 0.28241000 1.39581900 0.00001400

H -0.58992800 2.02691400 -0.00005100

C 1.56272600 1.91361100 0.00010300

C 2.68920000 1.09260100 0.00018500

C 2.59322900 -0.29438800 0.00018700

C 1.28531700 -0.89841500 0.00009500

O 1.05473600 -2.15500900 0.00008200

Cl 1.78804300 3.67787600 0.00011300

H 3.65631800 1.57017300 0.00025200

C 3.83965900 -1.19280700 0.00027800

C 3.83396600 -2.08746000 -1.26070100

H 4.69764000 -2.75873100 -1.25292900

H 2.92465900 -2.68197700 -1.29905000

H 3.88992400 -1.47562500 -2.16345700

C 5.14901200 -0.38571100 0.00027300

H 5.23812500 0.24839300 -0.88357900

H 5.23806600 0.24849800 0.88405600

H 5.99697100 -1.07362900 0.00034200

C 3.83389100 -2.08732000 1.26135700

H 2.92458300 -2.68183200 1.29971700

H 4.69756700 -2.75858900 1.25371100

H 3.88979500 -1.47538300 2.16404700

Compound E (cation)

Enthalpy= -1358.7143a.u.

O 5.26816100 1.01707800 0.00042300

H 4.29290300 1.08529400 -0.00258400

C 5.68076700 -0.24641300 0.00273000

O 6.84694600 -0.54373500 0.00863300

C 4.68410800 -1.38251400 -0.00220000

H 5.21827400 -2.32363400 -0.00330900

C 3.34209000 -1.46037500 -0.00401700

H 2.92061100 -2.45850700 -0.00639900

C 2.36679600 -0.36246800 -0.00326800

O 2.60861400 0.83146600 -0.00300400

N 1.03103000 -0.81959800 -0.00298100

H 0.90179500 -1.82141600 -0.00302100

C -0.11685900 -0.08081100 -0.00195300

C -0.17557900 1.31045800 -0.00161800

H 0.72338900 1.89904600 -0.00229100

C -1.42326200 1.89895300 -0.00035000

C -2.63260600 1.14439900 0.00071100

C -2.63951300 -0.23087100 0.00041200

C -1.35787700 -0.84578800 -0.00108400

O -1.16518500 -2.15863700 -0.00177300

H -1.99953000 -2.64907500 -0.00101100

Cl -1.55390800 3.60744000 0.00006400

H -3.55790000 1.69566500 0.00177600

C -3.94735200 -1.04854400 0.00160800

C -4.03491700 -1.92307700 1.27823900

H -4.98472900 -2.45540400 1.28357100

H -3.25490200 -2.68219400 1.36965600

H -3.98861000 -1.30881400 2.17674600

C -5.17445600 -0.11878800 0.00390000

H -5.20858300 0.51384200 0.89084500

H -5.21111800 0.51482700 -0.88223700

H -6.07769500 -0.72585400 0.00483900

C -4.03832200 -1.92129400 -1.27598500

H -3.25822500 -2.67990500 -1.37078300

H -4.98792700 -2.45400900 -1.27927800

H -3.99492600 -1.30573000 -2.17374400

Compound E (radical)

Enthalpy= -1358.3909a.u.

O -5.21809500 1.00706800 -0.00000300

H -4.22775900 1.05140300 -0.00057200

C -5.64748400 -0.24808500 -0.00017900

O -6.82456600 -0.52488000 0.00152800

C -4.66041500 -1.38548700 -0.00042100

C -3.32124500 -1.44900800 -0.00052100

C -2.33856900 -0.34276700 -0.00042500

O -2.62607200 0.85579300 -0.00029200

N -1.03996300 -0.77408100 -0.00040400

H -0.84531400 -1.77144300 -0.00044300

C 0.12866400 -0.04033800 -0.00020700

C 0.22430100 1.33593900 -0.00015100

C 1.50278800 1.88492400 0.00000800

C 2.67901700 1.10891300 0.00014100

H 3.61929700 1.63476900 0.00024300

C 2.64269000 -0.26425600 0.00011300

C 1.32708800 -0.90391200 -0.00010800

O 1.15144600 -2.13919400 -0.00022000

Cl 1.66333200 3.61649400 0.00000300

H -0.65231700 1.95889000 -0.00025100

H -2.88831800 -2.44233800 -0.00071000

H -5.19088900 -2.32819800 -0.00046600

C 3.91114000 -1.12089200 0.00019700

C 5.18286000 -0.25585200 0.00037300

H 5.24886600 0.37824400 -0.88474000

H 5.24886900 0.37789000 0.88573200

H 6.05577400 -0.90779800 0.00025100

C 3.93723900 -2.01104100 1.26625100

H 3.08802600 -2.68743700 1.29530300

H 4.85177800 -2.60561000 1.27209300

H 3.92974700 -1.40089100 2.17065400

C 3.93746600 -2.01085800 -1.26594500

H 4.85202700 -2.60540900 -1.27169600

Table 1S:

Some selected geometrical parameters calculated and experimental of compound Aat the B3LYP/6-31++G(2d, 2p) in gas phase, EtOH, DMSO, and water.

Exp.a / B3LYP
Gas / EtOH / DMSO / Water
Bond lengths (Å)
O1- C1 / 1.308 / 1.325 / 1.323 / 1.323 / 1.323
C1 - O2 / 1.217 / 1.210 / 1.218 / 1.218 / 1.219
C1 - C2 / 1.488 / 1.506 / 1.497 / 1.497 / 1.496
C2 - C3 / 1.325 / 1.340 / 1.340 / 1.340 / 1.340
C3 - C4 / 1.478 / 1.482 / 1.482 / 1.482 / 1.482
C4 - O3 / 1.239 / 1.234 / 1.242 / 1.243 / 1.243
C4- N1 / 1.337 / 1.363 / 1.353 / 1.353 / 1.353
N1 - C5 / 1.410 / 1.405 / 1.406 / 1.406 / 1.406
C5 - C6 / 1.393 / 1.394 / 1.395 / 1.395 / 1.395
C5 - 10 / 1.394 / 1.405 / 1.408 / 1.408 / 1.408
C6 - C7 / 1.382 / 1.388 / 1.387 / 1.387 / 1.387
C7 - C8 / 1.371 / 1.385 / 1.385 / 1.385 / 1.385
C7 - Cl1 / 1.741 / 1.754 / 1.763 / 1.763 / 1.763
C8 - C9 / 1.387 / 1.391 / 1.391 / 1.391 / 1.391
C9 - C10 / 1.383 / 1.383 / 1.386 / 1.386 / 1.386
C10 - O4 / 1.359 / 1.373 / 1.365 / 1.365 / 1.365
Bond angles (°)
O3 -C4 -N1 / 121.8 / 122.4 / 122.6 / 122.6 / 122.6
O3 -C4 -C3 / 123.8 / 124.3 / 123.9 / 123.9 / 123.9
N1 -C4 -C3 / 114.3 / 113.1 / 113.5 / 113.5 / 113.5
C4 -N1 -C5 / 129.4 / 129.3 / 129.5 / 129.5 / 129.5
C6 -C5 -C10 / 120.1 / 119.3 / 119.4 / 119.4 / 119.4
C6 -C5 -N1 / 124.1 / 124.7 / 124.7 / 124.7 / 124.7
C10 -C5 -N1 / 115.8 / 115.9 / 115.9 / 115.8 / 115.8
C7 -C6 -C5 / 118.5 / 119.2 / 119.1 / 119.1 / 119.1
C8 -C7 -C6 / 122.1 / 121.8 / 122.0 / 122.0 / 122.0
C8 -C7 -Cl1 / 118.9 / 119.3 / 119.4 / 119.4 / 119.4
C6 -C7 -Cl1 / 119.0 / 118.9 / 118.6 / 118.6 / 118.6
C7 -C8 -C9 / 119.1 / 119.0 / 118.9 / 118.9 / 118.9
C10 -C9 -C8 / 120.4 / 120.3 / 120.3 / 120.4 / 120.4
O4 -C10 -C9 / 123.7 / 123.4 / 123.4 / 123.5 / 123.5
O4 -C10 -C5 / 116.5 / 116.2 / 116.2 / 116.2 / 116.2
C9 -C10 -C5 / 119.8 / 120.4 / 120.4 / 120.3 / 120.3

Note: Refer to Figure 1 for numbers ; a[Ref. 2]

Table 2S: Calculated (B3LYP/6-311G++(2d,2p) values of BDE (in kcal/mol) for compounds A-E in gas-phase for OH, NH and CH bonds.

Compound / O4H / N1H / C1H / C2H / C6H / C8H / C9H
A / 75.4 / 95.6 / 107.2 / 104.4 / 112.5 / 112.0 / 113.3
B / 88.6 / 98.5 / 108.3 / 105.6 / 113.2 / 114.5 / /
C / 73.2 / 96.6 / 108.2 / 105.3 / 113.7 / 113.6 / /
D / 72.6 / 95.7 / 108.2 / 105.3 / 113.7 / 112.3 / /
E / 71.2 / 95.6 / 108.2 / 105.3 / 113.7 / 110.1 / /

Note: Refer to Figure 1 for atom numbering.

Table 3S: The enthalpy values (kcal/mol) of hydrogen atom, proton, electron and solvation corrections in vacuum and polar media (EtOH, DMSO, and water).

Chemical
individuum / Enthalpy (kcal/mol)
Vacuum / ∆HWater / Water / ∆HEtOH / EtOH / ∆HDMSO / DMSO
H(H+) / 1.48a / -260.5 d / -259.0 d / -249.8 b / -248.3b / -266.5 b / -265.0 b
H(H•) / -313.7 / -0.96 e,f / -314.6 / 0.9f / -312.8 / 1.2 b / -312.5
H(e-) / 0.74c / -25.1 b / -24.4 b / -18.2 b / -17.4 b / -20.1 b / -19.3 b

a[Ref. 3], b[Ref. 4], c[Ref. 5], d[Ref. 6], e[Ref. 7], f[Ref. 8]

Figure 2S: The rB3LYP/6-311++G(2d,2p) atomic orbital compositions of the frontier molecular orbital for compound A-E in vacuum. The calculations for canonical MOs were accomplished with isovalue 0.02

Figure3S:ROB3LYP/6-311++G(2d,2p) atomic SD values for radical of Compounds A-E in EtOH.

Figure4S:ROB3LYP/6-311++G(2d,2p) atomic SD values for radical of Compounds A-E in DMSO.

References of the ESI

1. C. Enroth, B.T. Eger, K. Okamoto, T. Nishino, T. Nishino, EF. Pai (2000) Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: Structure-based mechanism of conversion. Proc Natl Acad Sci USA 97: 10723–8.

2. Sirajuddin M, Nooruddin, S. Ali, V. McKee, S. Zeb Khan, K. Malook (2015) Synthesis, Spectroscopic Characterization, Crystal Structure, DNA Interaction Study and in Vitro Biological Screenings of 4-(5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic acid. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 134: 244–250.

3. Klein E, Rimarcik J, Lukes V (2009)DFT/B3LYP Study of the O–H Bond Dissociation Enthalpies and Proton Affinities of para- and meta-Substituted Phenols in Water and Benzene. Acta Chimica Slovaca. 2: 37–51.

4.Rimarcik J, Lukes V, Klein E, Ilcin M (2010) J. Mol. Struct.: TEOCHEM 952: 25–30.

5. Bartmess J E (1994) Thermodynamics of the Electron and the Proton. Phys. Chem. 98 (25):6420–6424.

6. Atkins P W (1998). Physical Chemistry, sixth ed., Oxford University Press, Oxford,.

7. Parker V D (1992) . J. Am. Chem. Soc. 114:7458–7462.

8. Bizarro M M, Cabral B J C, dos Santos R M B, Simoes J A M, (1999) Substituent effects on the O–H bond dissociation enthalpies in phenolic compounds: agreements and controversies + erratum Pure Appl. Chem. 71:1249–1256.