SEMIFLUORINATED SYMMETRICAL DIETHERS FOR INTRAOCULAR USE: SYNTHESIS, CHARACTERIZATION, AND IN VITRO BIOCOMPATIBILITY

Figures & data

Table 1. Synthesized Semifluorinated Diethers

Compound	M [g/mol]	b.p. [°C/mm Hg]	φ [g/cm^3]
(CF3CH2O)2(CH2)3	240	152/760	1.23
(CF3CH2O)2(CH2)4	254	76/16	1.21
(CF3CH2O)2(CH2)5	268	92/15	1.18
(CF3CH2O)2(CH2)6	282	107/18	1.16
(CF3CH2O)2(CH2)71^a	296	122/15	1.13
(CF3CH2O)2(CH2)81^a	310	137/15	1.11
(CF3CH2O)2(CH2)91^a	324	151/15	1.08
(CF3CH2O)2(CH2)101^a	338	166/15	1.06

b.p.: boiling point, φ: density.

^aNew.

Figure 1. Interfacial tension against H₂O; T = 21°C.

Figure 2. Surface tension; T = 25°C.

Table 2. Relative Complement Activation Induced by Semifluorinated Diethers

Test Compound	C3a Generation [% of Zymosan-Induced C3a]2^a
(CF3CH2O)2(CH2)3, n = 3	6.3	[0; 18.9]
(CF3CH2O)2(CH2)4, n = 3	4.7	[0; 14.1]
(CF3CH2O)2(CH2)5, n = 3	3.9	[0; 11.7]
(CF3CH2O)2(CH2)6, n = 3	5.1	[0; 13.8]
(CF3CH2O)2(CH2)7, n = 2	34.3	[33.9; 34.7]
(CF3CH2O)2(CH2)8, n = 2	0	[0; 0]
(CF3CH2O)2(CH2)9, n = 2	4.0	[0; 8.1]
(CF3CH2O)2(CH2)10, n = 2	19.6	[11.6; 27.1]

100% complement activation: C3a complement activation with zymosan; n: number of measurements.

^aConfidence interval.

Table 3. Effects on Interleukin-1β after Incubation of Mononuclear Leukocytes (MNL) with Semifluorinated Diethers (Tc) Plus or Without Lipopolysaccharide (LPS)

Test Compound (tc)	IL1β Concentration [pg/mL] MNL + tc + LPS	Suppression of IL1β[%]4^b	Induction of IL1β [% of LPS Induced IL1β IL1β]
None, n = 5	2411 ± 855	—	—
(CF3CH2O)2(CH2)3, n = 2	Negative3^a	100 [100; 100]	none
(CF3CH2O)2(CH2)4, n = 2	262 ± 337	93 [86; 100]	none
(CF3CH2O)2(CH2)5, n = 3	Negative3^a	100 [100; 100]	none
(CF3CH2O)2(CH2)6, n = 3	1380 ± 1020	48 [8; 80]	1
(CF3CH2O)2(CH2)7, n = 3	79 ± 104	96 [90; 99]	none
(CF3CH2O)2(CH2)8, n = 2	27 ± 1	99 [98; 99]	none
(CF3CH2O)2(CH2)9, n = 2	868 ± 327	55 [27; 83]	1
(CF3CH2O)2(CH2)10, n = 2	1372 ± 1903	62 [26; 98]	none

n: number of measurements.

^aBeyond detection limit.

^bConfidence interval.

Table 4. Relative ³H-Thymidine Incorporation of Hela and Raji Cells After Incubation with Semifluorinated Diethers

Test Compound	Hela rel. ^3H-thymidine Incorporation [%]	Raji rel. ^3H-thymidine Incorporation [%]
(CF3CH2O)2(CH2)3, n = 1	1	1
(CF3CH2O)2(CH2)4, n = 1	22	62
(CF3CH2O)2(CH2)5, n = 1	2	3
(CF3CH2O)2(CH2)6, n = 1	4	96
(CF3CH2O)2(CH2)7, n = 1	n.d.	n.d.
(CF3CH2O)2(CH2)8, n = 1	58	100
(CF3CH2O)2(CH2)9, n = 1	41	45
(CF3CH2O)2(CH2)10, n = 1	34	100

100% ³H-thymidine incorporation: incubation of the cells with culture medium; n.d.: not determined; number of measurements: 1.

Table 5. Cell Toxicity: Fraction of Dead Hela or Raji Cells After 24 h of Incubation

Test Compound	Hela Cells Fraction of Dead Cells After 24-h Incubation5^a	Raji Cells Fraction of Dead Cells After 24-h Incubation5^a
Medium, n = 4	8 [1; 12]	4 [0; 6]
Ringer's lactate, n = 4	10 [7; 15]	2 [0; 5]
(CF3CH2O)2(CH2)3, n = 2	100 [99; 100]	99 [99; 99]
(CF3CH2O)2(CH2)4, n = 2	73 [47; 98]	77 [56; 98]
(CF3CH2O)2(CH2)5, n = 1	86	100
(CF3CH2O)2(CH2)6, n = 2	73 [72; 74]	44 [20; 67]
(CF3CH2O)2(CH2)7, n = 2	88 [84; 91]	73 [65; 81]
(CF3CH2O)2(CH2)8, n = 3	74 [48; 93]	64 [52; 79]
(CF3CH2O)2(CH2)9, n = 4	53 [50; 59]	71 [67; 74]
(CF3CH2O)2(CH2)10, n = 4	54 [30; 82]	77 [66; 84]

n: number of independant measurements.

^aConfidence interval.