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Chemical Structure| 1089687-03-5 Chemical Structure| 1089687-03-5

Structure of 1089687-03-5

Chemical Structure| 1089687-03-5

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Product Citations

Product Citations      Show More

William E. Meador ; Eric Y. Lin ; Irene Lim ; Hannah C. Friedman ; David Ndaleh ; Abdul K. Shaik , et al.

Abstract: In vivo fluorescence imaging in the shortwave infrared (SWIR, 1,000-1,700 nm) and extended SWIR (ESWIR, 1,700-2,700 nm) regions has tremendous potential for diagnostic imaging. Although image contrast has been shown to improve as longer wavelengths are accessed, the design and synthesis of organic fluorophores that emit in these regions is challenging. Here we synthesize a series of silicon-RosIndolizine (SiRos) fluorophores that exhibit peak emission wavelengths from 1,300-1,700 nm and emission onsets of 1,800-2,200 nm. We characterize the fluorophores photophysically (both steady-state and time-resolved), electrochemically and computationally using time-dependent density functional theory. Using two of the fluorophores (SiRos1300 and SiRos1550), we formulate nanoemulsions and use them for general systemic circulatory SWIR fluorescence imaging of the in mice. These studies resulted in high-resolution SWIR images with well-defined vasculature visible throughout the entire circulatory system. This SiRos scaffold establishes design principles for generating long-wavelength emitting SWIR and ESWIR fluorophores.

Purchased from AmBeed: ; ;

William E. Meador ; Timothy A. Lewis ; Abdul K. Shaik ; Kalpani Hirunika Wijesinghe ; Boqian Yang ; Amala Dass , et al.

Abstract: Fluorescence-based biological imaging in the shortwave infrared (SWIR, 1000–1700 nm) is an attractive replacement for modern in vivo imaging techniques currently employed in both medical and research settings. Xanthene-based fluorophores containing heterocycle donors have recently emerged as a way to access deep SWIR emitting fluorophores. A concern for xanthene-based SWIR fluorophores though is chemical stability toward ambient nucleophiles due to the high electrophilicity of the cationic fluorophore core. Herein, a series of SWIR emitting silicon-rosindolizine (SiRos) fluorophores with emission maxima >1300 nm (up to 1550 nm) are synthesized. The SiRos fluorophore photophysical properties and chemical stability toward nucleophiles are examined through systematic derivatization of the silicon-core alkyl groups, indolizine donor substitution, and the use of o-tolyl or o-xylyl groups appended to the fluorophore core. The dyes are studied via absorption spectroscopy, steady-state emission spectroscopy, solution-based cyclic voltammetry, time-dependent density functional theory (TD-DFT) computational analysis, X-ray diffraction crystallography, and relative chemical stability over time. Optimal chemical stability is observed via the incorporation of the 2-ethylhexyl silicon substituent and the o-xylyl group to protect the core of the fluorophore.

Purchased from AmBeed: ; ; ; ; ;

Alternative Products

Product Details of [ 1089687-03-5 ]

CAS No. :1089687-03-5
Formula : C16H34Cl2Si
M.W : 325.43
SMILES Code : CCCCC(CC)C[Si](Cl)(Cl)CC(CC)CCCC
MDL No. :MFCD22370170
InChI Key :BXDGSXMFTGZLDT-UHFFFAOYSA-N
Pubchem ID :22023834

Safety of [ 1089687-03-5 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314-H227-H290
Precautionary Statements:P501-P210-P234-P264-P280-P370+P378-P390-P303+P361+P353-P301+P330+P331-P363-P304+P340+P310-P305+P351+P338+P310-P403+P235-P406-P405
Class:8
UN#:3265
Packing Group:

Computational Chemistry of [ 1089687-03-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 19
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 12
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 96.49
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

4.62
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

9.54
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

7.34
Log Po/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.

6.01
Log Po/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

5.58
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

6.62

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-7.08
Solubility 0.0000273 mg/ml ; 0.000000084 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-9.45
Solubility 0.000000115 mg/ml ; 0.0000000004 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly 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

-6.89
Solubility 0.0000423 mg/ml ; 0.00000013 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

Low
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

No
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

Yes
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

No
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

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-1.51 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

1.0
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

1.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

1.0
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

2.0
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

2.0 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<2.0
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)

5.02
 

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