168646-54-6|5,6-Diamino-1,10-phenanthroline| Ambeed

Abstract: The goal of this research was to design and study new systems of light activated molecules to deliver therapeutic agents. The impact of structural variation on spectroscopic properties as well as changes in photoinduced release of therapeutic molecules is reported herein. Chapter 2 reports complexes with the general structure [(bpy)2Ru(BL)Mn(CO)3Br](PF6)2 where the BL = 2,3-bis(2-pyridyl)pyrazine (dpp) and 2,2ʹ-bipyrimidine (bpm) and bpy = 2,2-bipyridine. Each of the bidentate bridging ligands exhibit different degrees of π-accepting ability when bridging two metal cations. The impact of the choice of bridging ligand on the photoactivated release of both CO and singlet oxygen (1O2) is reported. This report is the first example of a Ru(II),Mn(I) bimetallic complex with photoactivity in the phototherapy window (600 – 900 nm). The complexes were found to be stable in the dark and only released CO and singlet oxygen upon exposure to visible light. Chapter 3 extends the types of photoactivity of the complexes to include photoactivated DNA intercalation, along with CO release and 1O2 production. The framework used in this study was [(bpy)2Ru(tpphz)Mn(CO)3Br](PF6)2 where bpy = 2,2-bipyridine and tpphz = tetrapyrido[3,2-a:2′,3′-c:3′′,2′′-h:2′′′,3′′′- j]phenazine. The previously studied [Ru(bpy)2(tpphz)](PF6)2 complex has the ability to intercalate between the base pairs of DNA, which can inhibit cell proliferation, as well as a high production efficiency of singlet oxygen when exposed to light. This study used the 4 framework studied in chapter 2 and incorporated the tpphz as a bridging ligand component. The purpose of this study was to test if the addition of the Mn moiety would continue to allow interaction of the tpphz to DNA or inhibit it. The study found that the complex is stable in the dark and inhibits DNA intercalation in the dark. When exposed to visible light, the Mn component dissociates from the complex, freeing the tpphz to then intercalate into DNA. To the best of our knowledge, this is only the second reported photoactivated intercalative binding of an inorganic complex to DNA. Chapter 4 investigates the structure of the Mn(I) component on the energy of light required for photoactivation. A series of Mn(I) monometallic and bimetallic complexes were investigated for their ability to release CO when exposed to visible light. The framework studied was fac-[Mn(BL)(CO)3Br] and fac-[Br(CO)3Mn(BL)Mn(CO)3Br] for the monoand bimetallic complexes respectively where BL = 2,3-Bis(2-pyridyl)-pyrazine (dpp), 2,3-Bis(2-pyridyl)quinoxaline (dpq), and 2,3-bis(2-pyridyl)benzoquinoxaline (dpb). The bridging ligands, which have increasing π-accepting ability from dpp  dpq  dpb, allowed for lower energy absorbance and lower energy light required to release the CO. All of these complexes were able to release all CO molecules using visible light, which extended into the phototherapy window for some of the structures studied.

Purchased from AmBeed: 168646-54-6

Product Details of [ 168646-54-6 ]

CAS No. :	168646-54-6
Formula :	C₁₂H₁₀N₄
M.W :	210.24
SMILES Code :	NC1=C(N)C2=C(N=CC=C2)C2=NC=CC=C12
MDL No. :	MFCD12913573
InChI Key :	MNXMBMNXSPNINS-UHFFFAOYSA-N
Pubchem ID :	10910805

Safety of [ 168646-54-6 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Calculated chemistry of [ 168646-54-6 ] Show Less

Physicochemical Properties

Num. heavy atoms	16
Num. arom. heavy atoms	14
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	2.0
Num. H-bond donors	2.0
Molar Refractivity	65.85
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	77.82 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.97
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	1.1
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.96
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	0.67
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	1.47
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.24

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.48
Solubility	0.69 mg/ml ; 0.00328 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.33
Solubility	0.99 mg/ml ; 0.00471 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-4.29
Solubility	0.0107 mg/ml ; 0.0000511 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	Yes
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	Yes
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	Yes
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.8 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	3.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.66

Application In Synthesis [ 168646-54-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 168646-54-6 ]

[ 168646-54-6 ] Synthesis Path-Downstream 1~2

1
[ 2631-77-8 ]
[ 168646-54-6 ]
2-(2-hydroxy-3,5-diiodophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.9%	In ethanol; for 12h;Inert atmosphere; Schlenk technique; Reflux;	The ligand L3 was prepared by the following procedure. The mixture of <strong>[2631-77-8]3,5-diiodosalicylaldehyde</strong> (1.00 mmol, 1 equiv) and dap (1.00 mmol, 1 equiv) was refluxed in ethanol (20 mL) for12 h, then the mixture was concentrated under vacuo and cooled to room temperature. After filtration, the orange-yellow precipitate was washed three times by cold ethanol and dried in vacuo.Yield: 80.9%. Anal. Calcd for C19H10I2N4O (563.89): C 40.43, H1.79, N 9.93. Found: C 40.57, H 1.86, N 9.85. ESI-MS (m/z):564.9019 [M+H+] (calcd 564.9017); 562.885 [M-H+] (calcd562.886). 1H NMR (400 MHz, CD2Cl2, d, ppm): 14.14 (s, br, 2H, NH + OH), 9.08 (d, J = 2.8 Hz, 2H), 8.93 (s, br, 2H), 8.53 (s, br, 1H),8.15 (d, J = 2.0 Hz, 1H), 7.89 (s, br, 2H). IR spectrum (KBr, cm1):3444w, 3159m, 3121m, 3062s, 2965s, 2861s, 1609m, 1592m,1563m, 1539m, 1506m, 1582m, 1436s, 1402s, 1375m, 1356m,1296w, 1271m, 1256m, 1199w, 1178w, 1146w, 1123w, 1088w,1070m, 1049m, 1030m, 1002w, 976w, 940w, 880w, 864w, 800s,738s, 699w, 667m, 655m, 636m.

References: [1]Inorganica Chimica Acta,2017,vol. 457,p. 107 - 115.

2
[ 37091-73-9 ]
[ 168646-54-6 ]
C₂₂H₂₆N₈ [ No CAS ]

References: [1]European Journal of Organic Chemistry,2017,vol. 2017,p. 6085 - 6095.

Historical Records

Technical Information

• Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Chan-Lam Coupling Reaction • Hydride Reductions • Leuckart-Wallach Reaction • Mannich Reaction • Petasis Reaction • Preparation of Amines • Reactions of Amines • Specialized Acylation Reagents-Vilsmeier Reagent • Ugi Reaction

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P234	Keep only in original container.
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P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
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P378
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P391	Collect spillage. Hazardous to the aquatic environment
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P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
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H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
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H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
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H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
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H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
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H316	Causes mild skin irritation
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H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
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H333	May be harmful if inhaled
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H341	Suspected of causing genetic defects
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H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
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H412	Harmful to aquatic life with long-lasting effects
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H420	Harms public health and the environment by destroying ozone in the upper atmosphere

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Calculated chemistry of [ 168646-54-6 ] Show Less

Physicochemical Properties

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Medicinal Chemistry

Application In Synthesis [ 168646-54-6 ]

[ 168646-54-6 ] Synthesis Path-Downstream 1~2

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