NANOMATERIALS

1 . A compound of Formula (I):

wherein:

R 1 is C 9 -C 20 alkyl or C 9 -C 20 alkenyl with 1-3 units of unsaturation;

X 1 and X 2 are each independently absent or selected from —O—, NR 2 , and

wherein R 2 is C 1 -C 6 alkyl, and wherein X 1 and X 2 are not both —O— or NR 2 ;

a is an integer between 1 and 6;

X 3 and X 4 are each independently absent or selected from the group consisting of: 4- to 7-membered heterocyclyl optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, 5- to 6-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, and —NR 3 —, wherein each R 3 is a hydrogen atom or C 1 -C 6 alkyl;

X 5 is —(CH 2 ) b —, wherein b is an integer between 0 and 6,

X 6 is hydrogen, C 1 -C 6 alkyl, 5- to 6-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, or —NR 4 R 5 , wherein R 4 and R 5 are each independently hydrogen or C 1 -C 6 alkyl; or alternatively R 4 and R 5 join together with the nitrogen to which they are bound to form a 4- to 7-membered heterocyclyl optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, wherein the heterocyclyl optionally includes an additional heteroatom selected from oxygen, sulfur, and nitrogen;

X 7 is hydrogen or —NR 6 R 7 , wherein R 6 and R 7 are each independently hydrogen or C 1 -C 6 alkyl; or alternatively R 5 and R 7 join together with the nitrogen to which they are bound to form a 4- to 7-membered heterocyclyl optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, wherein the heterocyclyl optionally includes an additional heteroatom selected from oxygen, sulfur, and nitrogen;

at least one of X 1 , X 2 , X 3 , X 4 , and X 5 is present; and

provided that when either X 1 or X 2 is —O—, neither X 3 nor X 4 is

and when either X 1 or X 2 is —O—, R 4 and R 5 are not both ethyl.

2 . The compound of claim 1 , provided that

is not selected from the group consisting of:

3 . The compound of claim 1 , wherein R 1 is

4 . The compound of claim 1 , wherein the compound is selected from the group consisting of:

5 . A compound of Formula (II):

wherein:

R 8 is hydrogen or C 1 -C 6 alkyl;

R 9 is C 9 -C 20 alkyl optionally fused with 1-4 C 3 -C 6 cycloalkyl groups, C 9 -C 20 alkenyl with 1-3 units of unsaturation, or —(CH 2 ) g —X 17 , wherein X 17 is optionally substituted C 4 -C 12 cycloalkyl;

X 8 and X 9 are each independently absent or selected from —O—, NR 10 , and

wherein R 10 is C 1 -C 6 alkyl, and wherein X 8 and X 9 are not both —O— or NR 10 ;

X 10 and X 11 are each independently absent or selected from the group consisting of: 4- to 7-membered heterocyclyl optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, 5- to 6-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, and —NR 11 —, wherein R 11 is a hydrogen atom or C 1 -C 6 alkyl;

X 12 is —(CH 2 ) i —;

X 13 is hydrogen, C 1 -C 6 alkyl, 5- to 6-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, or —NR 12 R 13 , wherein R 12 and R 13 are each independently hydrogen or C 1 -C 6 alkyl; or alternatively R 12 and R 13 join together with the nitrogen to which they are bound to form a 4- to 7-membered heterocyclyl optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, wherein the heterocyclyl optionally includes an additional heteroatom selected from oxygen, sulfur, and nitrogen;

X 14 is hydrogen or —NR 14 R 15 , wherein R 14 and R 15 are each independently hydrogen or C 1 -C 6 alkyl; or alternatively R 14 and R 15 join together with the nitrogen to which they are bound to form a 4- to 7-membered heterocyclyl optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, wherein the heterocyclyl optionally includes an additional heteroatom selected from oxygen, sulfur, and nitrogen;

each of c, d, e, f, g, h, and i is independently an integer from 0-6;

at least one of X 8 , X 9 , X 10 , and X 11 is present;

R 16 is hydrogen or optionally substituted C 5 -C 6 aryl;

X 15 is optionally substituted C 4 -C 12 cycloalkyl or optionally substituted C 5 -C 10 aryl; and

X 16 is hydrogen or optionally substituted C 4 -C 12 cycloalkyl;

provided that when f is 1 and R 9 is

X 15 is not

6 . The compound of claim 5 , wherein R 9 is

7 . The compound of claim 5 , wherein R 9 is

8 . The compound of claim 5 , wherein i is 3, X 8 , X 9 , X 10 , and X 11 , are absent, X 13 is —NR 12 R 13 , and R 12 and R 13 are each methyl.

9 . The compound of claim 5 , wherein X 8 , X 9 , and X 11 are absent, i is 0, X 10 is

and X 13 is

10 . The compound of claim 5 , wherein c, d, and e are each 1.

11 . The compound of claim 10 , wherein R 9 is

12 . The compound of claim 11 , wherein R 8 is hydrogen.

13 . The compound of claim 5 , wherein R 9 and

are each

14 . The compound of claim 5 , wherein the compound is selected from the group consisting of:

15 . A lipid nanoparticle composition comprising:

a conformationally constrained ionizable lipid;

a phospholipid;

a polyethylene glycol-lipid;

a cholesterol; and optionally

a nucleic acid.

16 . The lipid nanoparticle composition of claim 15 , wherein the ionizable lipid is a compound of Formula (I):

wherein:

R 1 is C 9 -C 20 alkyl or C 9 -C 20 alkenyl with 1-3 units of unsaturation;

X 1 and X 2 are each independently absent or selected from —O—, NR 2 , and

wherein R 2 is C 1 -C 6 alkyl, and wherein X 1 and X 2 are not both —O— or NR 2 ;

a is an integer between 1 and 6;

X 3 and X 4 are each independently absent or selected from the group consisting of: 4- to 7-membered heterocyclyl optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, 5- to 6-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, and —NR 3 —, wherein each R 3 is a hydrogen atom or C 1 -C 6 alkyl;

X 5 is —(CH 2 ) b —, wherein b is an integer between 0 and 6;

X 6 is hydrogen, C 1 -C 6 alkyl, 5- to 6-membered heteroaryl optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, or —NR 4 R 5 , wherein R 4 and R 5 are each independently hydrogen or C 1 -C 6 alkyl; or alternatively R 4 and R 5 join together with the nitrogen to which they are bound to form a 4- to 7-membered heterocyclyl optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, wherein the heterocyclyl optionally includes an additional heteroatom selected from oxygen, sulfur, and nitrogen;

X 7 is hydrogen or —NR 6 R 7 , wherein R 6 and R 7 are each independently hydrogen or C 1 -C 6 alkyl; or alternatively R 6 and R 7 join together with the nitrogen to which they are bound to form a 4- to 7-membered heterocyclyl optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, wherein the heterocyclyl optionally includes an additional heteroatom selected from oxygen, sulfur, and nitrogen;

at least one of X 1 , X 2 , X 3 , X 4 , and X 5 is present; and

provided that when either X 1 or X 2 is —O—, neither X 3 nor X 4 is

and when either X 1 or X 2 is —O—, R 4 and R 5 are not both ethyl.

17 . The lipid nanoparticle composition of claim 15 , wherein the amount of ionizable lipid is present in the range of about 35 to 65 mole percent, based on total moles.

18 . The lipid nanoparticle composition of claim 15 , wherein the phospholipid is DSPC.

19 . The lipid nanoparticle composition of claim 15 , wherein the phospholipid is DMPC.

20 . A method of delivering a nucleic acid to a subject in need thereof, comprising administering to the subject the lipid nanoparticle composition of claim 15 .

21 . The lipid nanoparticle composition of claim 15 , wherein the nucleic acid is siRNA, miRNA, anti-sense oligonucleotide, or immunostimulatory oligonucleotide.

22 . The compound of claim 5 , wherein the compound is selected from the group consisting of: